Molecular Transducers of Physical Activity Consortium (MoTrPAC)

Frequently Asked Questions (FAQs)

General Questions


RFA-RM-15-010 and RFA-RM-15-011, Genomics, Epigenomics, and Transciptomics Analysis Sites (U24) and Metabolomics and Proteomics Chemical Analysis Sites (U24)


RFA-RM-15-012, Bioinformatics Center (U24)


RFA-RM-15-013, Preclinical Animal Study Sites (PASS) (U01)


RFA-RM-15-014, Consortium Coordinating Center (CCC) (U24)


RFA-RM-15-015, Molecular Transducers of Physical Activity Clinical Centers (U01)


General Questions

For More Information

Applications

MoTrPAC Operations/Interactions with Other MoTrPAC Components

Budget

Review

 

For More Information

Are the slides from the October 22, 2015, pre-application webinar available? Was it recorded?

The slides are available at https://commonfund.nih.gov/sites/default/files/MoTrPACWebinarSlides_PostWebinar_508.pdf. The webinar was not recorded, but the questions that we received are included here.

Where can I direct questions that are not answered here?

Please send your questions to PhysActMechanisms@mail.nih.gov.

Applications

Can an Institution apply for more than one of these Requests for Applications (RFAs)?

Yes.

How will milestones be developed in the planning process?

The milestones proposed by the applicant should be as reasonable as possible given the information in the RFA. The final milestones will be generated in the first year to reflect the agreed-upon project design and the need to complete the project in the time available. For instance, the milestones for the Chemical Analysis Sites will likely refer to the number of samples, the types of analyses, and the draft timelines for sample acquisition devised by the Steering Committee. For the Clinical Centers, the milestones will likely refer to recruitment goals and the timelines for biospecimen collection.

MoTrPAC Operations/Interactions with Other MoTrPAC Components

How will awardees interact with NIH?

This project uses a cooperative agreement funding mechanism, which mandates close interactions between awardees and NIH staff. Overall governance of the MoTrPAC will be conducted by a Steering Committee consisting of principle investigators and NIH staff. The Steering Committee will interact with an NIH Common Fund MoTrPAC Working Group (NIH staff who helped develop this project), which will provide policy information, manage the awards, and evaluate progress.

How will publications be handled? If assistant professors are involved, how will they be able to generate publications from this effort? Will there be a number of papers generated with a long list of co-authors?

Although the Consortium will write several core papers, this rich dataset is intended to give rise to a very large number of publications authored by small groups of investigators. A publication subcommittee of the Steering Committee will likely be established to oversee Consortium publications.

Who will be eligible to apply for MoTrPAC Opportunity Funds?  Will these be only open to the clinical centers?

The Opportunity Funds, if they become available, will be an open competition with a goal to enhance the overall MoTrPAC project.

Budget

The RFAs state that "The Steering Committee will meet in person three times during the first year..." and "Applicants should plan to attend an initial planning meeting of the Steering Committee in Bethesda, Maryland, on October 13-14, 2016." Is the planning meeting to be held in October 2016 in addition to 3 in-person Steering Committee meetings in the first year, or is it counted as one of the 3 in-person Steering Committee meetings?

It is one of the 3 planned in-person meetings.

Review

Should an applicant suggest reviewers so that the appropriate expertise is available on the review committee? Should an application include letters of support from experts in the research community?

An applicant is welcome to list the expertise required for review in the cover letter, but should not suggest particular individuals, as these people may be placed in conflict as a result. An applicant should include letters of support only from those scientists who will directly participate in the proposed work, as they will be in conflict and unable to participate in review.

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RFA-RM-15-010 and RFA-RM-15-011, Genomics, Epigenomics, and Transciptomics Analysis Sites (U24) and Metabolomics and Proteomics Chemical Analysis Sites (U24)

Applications/Applicant Team

Techniques and Expertise

MoTrPAC Operations/Interactions with Other MoTrPAC Components

Budget

 

Applications/Applicant Team

May an applicant propose a consortium of sites that would work together to do the required analysis?

Yes, several institutions can work together to provide a set of appropriate analyses. The award would go to the applicant institution, and the others would receive subcontracts from that institution.

Should a Chemical Analysis Site have exercise expertise on the team? Should the Multiple Principal Investigator (PI) mechanism be used, so that the application has a PI with technical expertise and a PI with exercise expertise?

The Chemical Analysis Site would benefit from exercise expertise to inform its proposed tissue analysis plan and to work with the Steering Committee to finalize an overall MoTrPAC tissue analysis plan during the planning year. Applicants’ tissue analysis plan should be justified in terms of the current state of knowledge and the analyses most likely to provide important information regarding the molecules that respond to exercise. The applicants must decide on the most productive structure for its leadership. Reviewers will evaluate the scientific and administrative need for all PIs, the qualifications for leadership of all PIs, and the benefit to the project of the leadership structure.

May an applicant for the Genomics/Epigenomics/Transcriptomics funding opportunity announcement propose proteomics and metabolomics assays, and vice versa?

If an applicant wishes to propose substantial analyses that fall into both RFA-RM-15-010 and RFA-RM-15-011, the best approach is likely to submit applications to both RFAs rather than one application with combined analyses. If an applicant wishes to propose mostly analyses that fall into one, with a small fraction that falls into the other, a single application may be appropriate.

Techniques and Expertise

Will sites need to perform all aspects of transcriptional profiling or can sites focus on one specific molecular transducer?

An application should propose analyses that lie within the strengths and interests of the applicant. It can be very broad in scope. On the other hand, if the proposed analyses is highly specialized or very important for the project, it could be quite narrow, and the proposed budget should reflect the scope. The intention is to assemble an appropriate range of assays, whether within one site or among several sites. The review process will focus on scientific and technical quality, the power for the proposed assays to contribute to knowledge of the likely molecular transducers of physical activity, and evidence that the site has sufficient capacity for the project.

May an applicant propose a small analysis site with highly specific analysis that requires rare expertise or technology?

Yes, an applicant can propose a small analysis site if it possesses particular highly specialized, important analyses that are likely to add considerable value. The budget should reflect the scope.

Metabolomics still has many unknowns, so can chemical analysis sites include a core for characterizing the unknowns?

Yes. An applicant can, but is not required to, propose a core for identifying unknown molecules. Such identification is likely to be important for the success of the project.

MoTrPAC Operations/Interactions with Other MoTrPAC Components

Would there be a standardized process for specimen collection (time of day, diet, etc.) to avoid variability?

Applicants should address all study design and experimental parameters likely to affect the quality of the resultant data.

How much material will be supplied by the clinical and animal sites for analysis?

An application for a Chemical Analysis Site should indicate how much tissue is needed for each assay, while a Clinical Center application should indicate how much tissue will be provided. In planning the RFAs, it was assumed that skeletal muscle biopsies will be approximately 150 milligrams, while adipose tissue biopsies will be approximately 1 gram.

How will the samples be distributed among analysis centers?

It is anticipated that the Consortium Coordinating Center will establish a central tissue repository, to which Clinical Centers and Preclinical Animal Study Sites will submit their tissues, and from which tissues will be distributed to the Chemical Analysis Sites according to their analysis plans.

Budget

Will it be possible to repurpose funds depending on the progress/discoveries between and within Chemical Analysis Sites?

A site will be able to rebudget funds among its activities as needed. The Steering Committee will undertake decisions regarding changes in the tissue analysis plan that may arise as data is collected. It is possible that the NIH could reapportion funds to some extent among the Chemical Analysis Sites in response to changes made by the Steering Committee in the Tissue Analysis Plan.

If multiple sites are selected for global profiling, should the first-year budget reflect costs associated with interlab testing to standardize analysis between selected sites?

Funds for the first year are limited, but awarded sites could plan during that first year for standardization activities to take place as soon as second-year funding is available.

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RFA-RM-15-012, Bioinformatics Center (U24)

Data and Software Distribution

MoTrPAC Operations/Interactions with Other MoTrPAC Components

Review

 

Data and Software Distribution

Data and software dissemination activities to promote access to MoTrPAC data to biomedical researchers is likely to extend beyond the 6 years of funding currently allotted. What are the plans for extended funding for these activities?

Although it is expected that the human exercise study will be completed within the 6 year project period, other activities, particularly data analysis, may continue beyond that time and applicants may need an extension into year 7. The need for additional funds will be evaluated during the final year of the project period.

MoTrPAC Operations/Interactions with Other MoTrPAC Components

How will policies on public sharing of the proprietary computing resources developed?

All resources developed using NIH funds under these RFAs must be shared as governed by NIH sharing policies.

Will the Bioinformatics Center or the Consortium Coordinating Center (CCC) be responsible for the creation and maintenance of the MoTrPAC database?

The Bioinformatics Center will largely be responsible for creating the MoTrPAC data resource. The CCC and the Bioinformatics Center will work together to ensure that the CCC has appropriate data resources. The CCC will manage the flow of data between funded sites and ensure data quality.

Review

Will bioinformatics center be assessed on inclusion of investigators familiar with physical activity and molecular transducers, or is the informatics expertise and track record more important?

The Bioinformatics Center applications will be judged on the ability of the PI and team to accomplish the goals of the study as outlined in the RFA, which is highly dependent on bioinformatics expertise. Exercise expertise is not required for the bulk of the Bioinformatics Center's work. Exercise and chemical analysis expertise consultation could be valuable to inform the application, but those experts will be part of the Consortium and do not need to be budgeted by the Bioinformatics Center.

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RFA-RM-15-013, Preclinical Animal Study Sites (PASS) (U01)

Applications/Applicant Team

Animal Models and Exercise Protocols

Functional Studies

MoTrPAC Operations

Budget

Second Preclinical Animal Studies Funding Opportunity Announcement (FOA)

 

Applications/Applicant Team

Can two laboratories collaborate on one PASS application? Can separate applications from two labs propose synergistic experiments?

Yes.

Animal Models and Exercise Protocols

Which animal model should I propose to work on?

The proposed model for Phase 1 studies should be chosen to best complement the clinical data, while balancing cost and availability. For Phase 2 studies, a mix of models may be needed, including transgenic mice and human cell lines.

Will mice or non-human primates be considered as candidate species for exercise studies?

Applicants should propose those models they feel best complement the human studies, while balancing cost and availability. They should be willing to work with other awardees on a common model during the Phase 1 study.

Will each PASS do both endurance and resistance exercise with the animals?

It is possible to imagine either a model where each PASS does both endurance and resistance exercise or one where each lab focuses on a different type of exercise. Applicants should propose the best study based on their expertise and experience.

Do you expect animal exercise programs to be 12 weeks?

Applicants should propose the study that they feel best complements the human study and indicate a willingness to work with the other PASS to finalize the study plan.

Functional Studies

What kind of functional assays should be proposed in Phase 2?

It is likely that each investigator will propose to investigate tissues, pathways, systems, mechanisms, etc., that are known to be affected by physical activity, are expected to be involved in the health benefits, and are well within the investigator’s own interests, expertise, and lines of research. It is unlikely that any one application could propose a comprehensive set of Phase 2 studies, but it is hoped that a group of applications could be identified that together will shed light on the mechanisms by which physical activity provides health benefits.

Although awards are for Preclinical Animal Study Sites, may investigators propose studies using human cells for some of their Phase 2 mechanistic studies?

Yes.

If new molecules are discovered, how do we get the compound to work with?

A PASS could have an interesting molecule produced for its own study. If the Consortium considers a molecule that is otherwise unavailable important for study, it could make arrangements to have that compound produced and made available to all PASS.

MoTrPAC Operations

Will there be assistance with common Institutional Animal Care and Use Committee (IACUC) among institutions?

NIH will not mandate use of a single IACUC approval process. It is likely that the Steering Committee will discuss this issue shortly after the Consortium forms. If common IACUC approval processes are deemed to be the most efficient way forward, the NIH and the Consortium Coordinating Center will provide assistance.

Budget

PASS are expected to begin to generate tissues at the end of the first year, but the first-year budget is for planning activities only. How will the first-year research activities be supported?

It may be possible to 're-cycle' awards such that the second year starts less than 12 months after the first year of the award begins.

Will tissues be processed at the PASS sites or at the Chemical Analysis Sites? The answer has implications for the budget.

There are many unknowns that are likely to impact budgets at the various components of the MoTrPAC. An applicant may make an educated guess regarding the costs of tissue handling and processing. If necessary, budgets will be adjusted starting in year 2 to ensure that tissues can be handled appropriately.

Second Preclinical Animal Studies Funding Opportunity Announcement (FOA)

Will PASS grantees be eligible to apply to the second Preclinical Animal Study Sites FOA? When will the second FOA be released?

NIH anticipates funding 5-7 additional Preclinical Animal Study Sites in FY 2018 to complement the Phase 2 mechanistic work being done by the awardees who are funded under RFA-RM-15-013. The second FOA will likely be issued when there is significant human data available and need for more investigators to increase throughput. These awards will be for 3-4 years (ending in FY 2021). Awardees from RFA-RM-15-013 will likely not be eligible to apply for the second FOA, as they will already be funded for mechanistic studies during the same time period (funding under RFA-RM-15-013, which also will end in FY 2021).

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RFA-RM-15-014, Consortium Coordinating Center (CCC) (U24)

Data and Specimen Storage and Distribution

Opportunity Funds

MoTrPAC Operations/Interactions with Other MoTrPAC Components

 

Data and Specimen Storage and Distribution

Will the CCC need to store physical data or specimens on-site?

The CCC will store and manage some primary data. The CCC will contract with a biospecimen repository and also coordinate biospecimen storage and shipment between funded sites during the study period. Late in the study, CCC and Steering Committee (working with the NIH) will arrange for a permanent repository of specimens for use by future investigations.

Is the CCC expected to develop and maintain a central biospecimen repository? If so, is the budget of this facility, including shipping, aliquoting, and supplies, expected to be contained within the CCC’s budget?

Yes, the CCC should budget for sample storage and distribution during the study, and propose a permanent repository at the end of the study.

Given that data analysis and storage are covered under the Bioinformatics Center and Chemical Analysis Sites, what types of shared, open-sourced software is the CCC expected to develop?

The CCC will use software relevant to the role of the CCC (e.g., for clinical data management, tracking of data and specimens, reporting). The CCC might not develop software; if it does, the software will be shared and open-sourced.

Will the CCC be responsible for the creation and maintenance of the MoTrPAC database?

The Bioinformatics Center will largely be responsible for creating the MoTrPAC data resource. The CCC and the Bioinformatics Center will work together to ensure that the CCC has appropriate data resources. The CCC will manage the flow of data between funded sites and ensure data quality.

Will the CCC be responsible for determining levels of access to the MoTrPAC database (e.g., what identifying information can be shared/not shared to different investigators)?

The CCC will work with the Bioinformatics Center to ensure appropriate data access.

Will the CCC need to distribute raw data inside the study or merely summaries?

The level of the data distribution and analysis will be discussed by the Steering Committee with the intention of protecting participant privacy, ensuring that the study outcomes are not compromised, and allowing sufficient data analysis to inform Consortium activities as the study proceeds.

Data and software dissemination activities to promote access to MoTrPAC data to biomedical researchers is likely to extend beyond the 6 years of funding currently allotted. What are the plans for extended funding for these activities?

Although it is expected that the human exercise study will be completed within the 6 year project period, other activities, particularly data analysis, may continue beyond that time, and applicants may need an extension into year 7. The need for additional funds will be evaluated during the final year of the project period.

Opportunity Funds

Is a CCC applicant required to describe a MoTrPAC Opportunity Funds Program?

Yes, an applicant should describe an Opportunity Funds Program in the event that money becomes available. This Program could be used to solicit applications for projects such as ancillary clinical studies, pilot tissue analyses, identification or production of specific molecules, or novel cell-based systems for specific uses. The proposal should briefly describe how applications would be solicited, reviewed, selected under the auspices of the Steering Committee, and awarded. Applicants should assume that funds would be disbursed through the CCC.

What years would the Opportunity Funds be administered?

When, and if, funds become available, it is anticipated that the funds would be administered potentially in years 2 through 6.

How will Opportunity Fund projects be selected? Should plans for the Opportunity Fund be incorporated into the CCC applications? If so, how much should be budgeted?

The CCC applicant should not request Opportunity Fund dollars in the application. If funds become available, they will be distributed as a supplement from the NIH to the appropriate award. However, the CCC application should contain a plan for administering a peer reviewed program to support the Opportunity Funds Program.

Who will be eligible to apply for MoTrPAC Opportunity Funds?  Will these be only open to the clinical centers?

The Opportunity Funds, if they become available, will be an open competition with a goal to enhance the overall MoTrPAC project.

MoTrPAC Operations/Interactions with Other MoTrPAC Components

Will the coordinating center take care of costs of study forms, data entry, data quality assurance, and long-term specimen storage? Will they also do the randomization programs?

Yes.

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RFA-RM-15-015, Molecular Transducers of Physical Activity Clinical Centers (U01)

Applications/Applicant Team

Adult Centers

Pediatric/Adolescent Center

Data and Specimen Collection and Analysis

MoTrPAC Operations/Interactions with Other MoTrPAC Components

Budget

Review

 

Applications/Applicant Team

Can an institution submit an application for an Adult Clinical Center and a separate application for a Pediatric Clinical Center?

Yes, this is possible.

Is it permissible to submit a multiple PI (MPI) plan?

Yes, NIH allows multiple Principal Investigators (PIs), provided the applicant(s) clearly justifies the rationale and specific roles of each PI. These roles should be distinct and clearly articulated in the application. Please note that each Center (irrespective of the number of PIs) will have one vote on the Steering Committee.

What is the role of the Clinical Center biostatistician?

The role is the same as for any clinical trial, as outlined in the application Statistical Analysis Plan: to help plan cohort sizes and number/type of biospecimens using appropriate statistical arguments, ensure proper randomization, and ensure that all measures are appropriate and can be interpreted.

Can applicants budget for their own statistical and informatics support to ensure adequate interoperability with the Study Coordinating Center?

Yes. The clinical center biostatistician will help plan cohort sizes and number of biospecimens using appropriate statistical arguments, ensure proper randomization, and ensure that all measures are appropriate and can be interpreted. Please note that because a separate Bioinformatics Center (RFA-RM-15-012) is part of this initiative, applicants should justify their requests for informatics support in their applications. As noted elsewhere, decisions regarding the final sample size and design of the overall clinical study will be made during the planning phase (Phase 1, year 1).

In section IV (application and submission information) of the RFA, a Clinical Protocol Synopsis, a Statistical Analysis Plan, and a Data and Safety Monitoring Plan (DSMP) are requested. However, there is also a request for a Research Strategy section; is this redundant with the Protocol Synopsis?

The Research Strategy section needs to focus on the primary elements that applicants typically need to include in this section, whereas the required appendices will enable applicants to more fully describe their Clinical Protocols, Statistical Analysis Plan, and DSMP. These three sections, which will nevertheless be somewhat abbreviated, should provide greater detail than what is possible in the Research Strategy section because of space limitations.

Is there a template available for the Clinical Protocol Synopsis?

There is no template for the Clinical Protocol Synopsis, but the elements that should be included in the synopsis are itemized in the Clinical Centers RFA.

The RFA states that a single central Institutional Review Board (IRB) may be used to streamline the approval process. Is this a decision that NIH program officials will make or should applications suggest a central IRB plan?

Applicants may suggest a central IRB plan, but this is not required. After award, the Consortium will make the decision about whether to use a single central IRB plan. Applicants may express their institution’s willingness to use a central IRB, but this will not be considered in review.

Are there page limits for the required Other Attachments (i.e., Clinical Protocol Synopsis, Statistical Analysis Plan, DSMP)?

*Updated November 24, 2015* The number of pages is not limited. The RFA outlines the elements (as a bulleted list) of the Clinical Protocol Synopsis and DSMP, as well as the key components of the Statistical Analysis Plan, that need to be addressed. However, applicants should keep in mind that the attachments should provide critical information but without an excessive amount of material that will pose undue challenges to the reviewers.

What constitutes a ‘specific plan for sharing software’?

Although Clinical Centers are unlikely to produce software under this award, applicants must agree to follow the guidelines in the RFA in the event that they produce software. This plan need not be more than a sentence or two.

Adult Centers

The RFA states that “all study participants must be healthy and capable of participating in physical activity interventions.” Could eligible individuals with chronic diseases, particularly older individuals, be enrolled? How will healthy be defined?

*Updated November 9, 2015* This RFA has specified that participants should be healthy and able to participate fully in the exercise protocols. Some individuals with chronic diseases might be eligible, provided the disease is well-controlled (e.g., hypertension, atherosclerotic cardiovascular disease, osteoporosis, osteoarthritis, thyroid dysfunction) and they are able to participate safely and fully in the prescribed single bout of exercise and exercise program. It is expected that applicants will describe eligibility criteria for all participants, including appropriate age and health characteristics. Definitions of "healthy" should be presented by the applicants, keeping in mind scientifically accepted definitions and cut-offs. Final eligibility criteria will be determined by the Consortium during the initial planning phase of the clinical study.

Should the study population include obese individuals? Is obesity considered a disease?

It is expected that a range of BMIs will be included. All participants must be able to accomplish all of the proposed physical activity exercise protocols.

Should Clinical Centers propose to focus on a single age group (i.e., young adults, middle-age adults, older adults) or propose to enroll adults across the age span?

Different sites may specialize in different ages, but keep in mind that NIH expects a wide age range represented across the Clinical Centers. Whatever ages or other characteristics you propose, these must be justified carefully. If you limit the recruitment to a specific age group, include the Center’s capability to recruit more widely to satisfy the needs of the Consortium

Should applicants propose recruiting a subject population that matches the national demographics?

Across the entire multi-center study, NIH expects the study population to be enriched in minorities and to include all ages (from children to the elderly).  Each Center will contribute to the overall study population although it might not provide the entire distribution itself.  Applicants will need to use their local demographics when planning their recruitment strategies, keeping in mind the program’s overall goals. .

Will pregnant women be excluded?

Yes.

How many participants should be enrolled per site?

Up to 6 clinical centers will recruit adult participants. Each clinical center should have the capacity to enroll up to 450 participants during a four-year period. This number includes the two physical activity and two comparator groups. One Clinical Center will recruit ~300 children and adolescents. Clinical Center applicants should provide demographic and other relevant details (age, ethnicity, BMI, etc.) for potentially eligible participants in their local area, based on their experience with previous studies.

May I propose that a different number of participants be studied?

Yes, applicants may propose to enroll a modified number of participants, provided the proposed numbers are very well-justified and based upon their experience. Please be mindful that the final study design, including sample size, will be determined by the Consortium during year 1 (planning).

May I use subcontracts to add additional sites to recruit participants?

Yes, applicants may use subcontracts to add additional sites, if their Clinical Center will not be able to enroll the entire sample size within the duration of the study period. However, applicants need to be aware of the fiscal constraints as additional sub-contracted sites are included as part of their Center.

Since recruitment is generally a challenge in multi-center studies, will there be a vanguard (run-in) phase to ascertain whether Centers are able to recruit prior to the issuance of year 2 funds?

No. The clinical study will move into the operational phase following the recommendation of the DSMB and final approval of NIH.

What will the exercise protocols be for adults?

Adult sedentary participants will be exposed to an acute bout of exercise with sample collection at baseline and subsequently randomized to a ~12-week endurance or resistance training program, followed by another acute bout with sample collection. Smaller in number comparison groups will include sedentary controls and highly fit individuals who will not participate in the physical activity training programs. Applicants should propose the type, intensity, duration, frequency, and other relevant details for both the acute exposure and the training program. Applicants should also propose and justify the number of participants per group, how they will be selected, and the statistical basis for determining group sizes.

Do I have to propose both a resistance and an endurance exercise program to be conducted at my Center, or can I choose only one or the other? Can I propose a mixed exercise training program using elements of both strength and endurance exercise?

Clinical Centers must randomize participants to each of two physical activity training programs, endurance or strength exercise. Mixed exercise training programs may obscure the distinct molecular signals expected to arise from either a resistance or endurance exercise program.

Does the 450 enrolled per site include the 2 control groups (i.e., sedentary randomized to no exercise and exercise trained individuals)? Or is each site expected to exercise train 450 individuals (225 endurance + 225 resistance) and then enroll additional subjects into the control groups (studying more like 600 total)?

Up to 6 Clinical Centers will recruit adult participants. Each Clinical Center should have the capacity to enroll up to 450 participants during a four year period. This number includes the two physical activity and two comparator groups.

Is the expectation that Clinical Centers will randomize sedentary volunteers to 3 groups (endurance, resistance, and no exercise control) or 2 groups (endurance and resistance training)?

Clinical Centers will randomize sedentary volunteers to endurance, resistance, and no exercise control groups. The highly fit and no exercise control groups will be smaller in number than the endurance and resistance groups.

Will all participants receive the same acute exercise bout? Children and adults, or individuals with a variety of initial capacity may have much different abilities to complete an exercise session.

The acute exercise bout will be designed according to what applicants propose and what the Consortium decides during the planning phase (year 1) of the study. Applicants will need to determine the eligibility criteria and the parameters of the exercise regimen, as well as the type, intensity, duration, and frequency of the training regimen, based upon clear rationale, yet recognizing that all Centers will use one common protocol as determined by the Consortium.

When/what assessments must be done? Is there an expectation that certain factors will be controlled (e.g., body weight, diet composition) to ensure that physical activity is the only factor that changes, or should such factors be allowed to vary?

Applicants should justify the critical factors that they deem necessary to take into account in the design of the study. Participants must be well-characterized at baseline with respect to age, sex, and objective physiologic, morphometric, and metabolic fitness measures. Biospecimens will be collected before and after the initial acute bout of exercise and again after an acute bout of exercise at the conclusion of the training program. Applicants should propose the type, intensity, and timeline of the physical activity exposures and other appropriate factors in the assessment protocol. The well-justified physiologic, morphometric, metabolic, and other health-related fitness evaluations will be used to characterize all participants at baseline, to adequately capture covariates that will be used in the statistical analyses, to relate these physiologic outcomes to the molecular transducers, and to relate these physiologic outcomes to the existing literature.

How will the final protocol be determined?

Each applicant should propose and justify the study he or she believes will best address the objectives of this funding opportunity and the design that is most appropriate for his or her participant population. However, the final study design will be determined by all awarded Clinical Center PIs working together with other members of the MoTrPAC Steering Committee. All of the Clinical Centers will be expected to conduct the randomized clinical study using a common protocol (determined by the Steering Committee), collect common data elements, use standardized procedures (including standard tissue acquisition and sample storage), submit all data to the data repositories, and complete other activities as determined by the Steering Committee.

Once the common protocol is set, will individual sites have the ability to add-on measures or different populations of interest?

Ancillary and sub-studies are expected. Investigators will need to seek additional funding for these activities and will need prior approval from the Steering Committee to engage in ancillary or sub-studies.

Would a free-living style intervention focusing on integration of moderate intensity physical activity into participants’ daily lives be within the scope and spirit of the goals of the project?

Applicants are free to propose whatever they feel is the best training strategy. Interventions should elicit measureable physiological changes in order to ensure that they will uncover changes in molecular transducers associated with a robust exposure to chronic physical activity. They should be implementable at all of the awarded Centers so that each can deliver a comparable training challenge. If possible, applicants should propose endurance and resistance training strategies because the project is intended to capture differences, should they exist, between these two types of exercise.

Pediatric/Adolescent Center

How many participants should be enrolled?

One Clinical Center will recruit ~300 children and adolescents. Clinical Center applicants should provide demographic and other relevant details (age, ethnicity, BMI, etc.) for potentially eligible participants in their local area, based on their experience with previous studies.

May I propose that a different number of participants be studied?

Yes, applicants may propose to enroll a modified number of participants, provided the proposed numbers are very well-justified and based upon their experience. Please be mindful that the final study design, including sample size, will be determined by the Consortium during year 1 (planning).

May I use subcontracts to add additional sites to recruit participants?

Yes, applicants may use subcontracts to add additional sites, if their Clinical Center will not be able to enroll the entire sample size within the duration of the study period. However, applicants need to be aware of the fiscal constraints as additional sub-contracted sites are included as part of their center.

What will the exercise protocols be for children?

Children and adolescents of different ages/stages of development will be exposed to an acute bout of physical activity, with the type, intensity, and duration proposed by the applicant. With appropriate justification, applicants may also propose to conduct a short-term (~12-week) exercise training program in a sub-sample of participants to assess molecular transducers of physical activity. The design of the physical activity training program(s) will be proposed by applicants, but should be age/developmentally appropriate and well-justified.

Will the Pediatric/Adolescent Clinical Center be asked to recruit both highly active and sedentary children, similar to the Adult Centers?

NIH expects the Pediatric/Adolescent Clinical Center to recruit children and adolescents with a wide range of habitual physical activity, rather than to recruit distinct groups of highly active and sedentary children.

Does the Pediatric/Adolescent Center need to propose both endurance and resistance training programs, or just one of these?

*Updated November 9,2015* Pediatric/Adolescent Center applicants need not propose a training program.  If a training program is proposed, the type, intensity, duration and frequency of the exercise training should be well-justified and draw upon the Center personnel’s experience and expertise.

Can the Pediatric/Adolescent Clinical Center enroll participants younger than 12 and older than 18 years of age?

The RFA specifically indicates that the Pediatric/Adolescent Clinical Center is expected to enroll 300 healthy children/adolescents 12 to 18 years of age. NIH would very strongly discourage prospective Pediatric/Adolescent Clinical Centers from proposing to enroll individuals younger than 12 years of age or adults (defined by NIH as >18 years of age). The Adult Clinical Centers will enroll individuals 18 years of age or older.

Data and Specimen Collection and Analysis

Given that the aim of the Clinical Centers’ purpose is to “collect biospecimens for analysis using genomics, transcriptomics, epigenomics, metabolomics, and proteomics for the discovery of the entire range of molecular transducers that underlie the effects of physical activity in humans,” should applicants specify discrete specific aims apart from “to collect XX samples for profiling” in the Specific Aims and Research Strategy sections?

Each applicant for the Clinical Centers is likely to have unique scientific goals, either in addition to the collection of tissues for analysis or as part of that effort. These goals are expected to be a large part of an applicant’s justification for the proposed exercise interventions and for the statistical arguments on which the proposed cohort size and characteristics to be measured are based. 

Although long-term training programs, studies focused on health outcome assessments (e.g., cardiovascular disease, diabetes, or body weight-related outcomes such as weight loss) associated with physical activity are not appropriate for this RFA, can studies collect data on risk factor (blood lipid, blood glucose, blood pressure) changes as part of their assessments?

Yes, but applicants must fully justify any risk factor assessments in their applications, as well as consider participant burden.

Are the collection of psychological variables (e.g., depression attributes) acceptable?

Collection of such variables would need to be very well justified and convincingly presented because psychological factors are not the focus of this RFA.

Will the Clinical Centers RFA support imaging studies, such as DXA or MRI?

The budget is unlikely to support the use of MRIs but may accommodate DXA scans for body composition. DXA scans would need to be justified scientifically.

Should applicants include comparisons of adult and pediatric data within their analytic plans?

No.

What biospecimens need to be collected in adults? Does each center need to collect blood, muscle tissue, and adipose tissue from every enrolled participant?

Biospecimens from adults must include a minimum of blood, skeletal muscle tissue, and subcutaneous adipose tissue. Blood must be collected from every participant. However, applicants may propose to collect muscle and adipose tissue from a robust sub-sample at critical time points, as long as cogent justification is indicated in the application. Applicants must have the demonstrated capability to collect, process, temporarily store, and ship the specified samples. Applicants may also propose to collect additional types of biospecimens/samples (e.g., urine, saliva) with appropriate justification.

What biospecimens need to be collected in children/adolescents?

For children and adolescents, biospecimen collection must include blood at a minimum. Additional biospecimens (e.g., urine, saliva, muscle tissue, adipose tissue) may be proposed, if possible and age-appropriate, with appropriate justification.

Does MoTrPAC anticipate collecting tissue sub-fractions (e.g., exosomes, isolated stem cells, mitochondria) as well as whole tissue specimens?

There may be considerable value in processing tissues in order to obtain some subfractions for study. Applicants should propose tissue processing and subfractions that they feel are particularly valuable to inform the discovery of molecular transducers of physical activity. The Steering Committee will make final decisions during the first year of planning the study.

How much sample will be expected to be available from invasive sampling?

Applicants should state how much tissue they expect to be able to harvest for each biopsy. In planning the RFAs, it was assumed that skeletal muscle biospecimens would be approximately 150 milligrams and that adipose tissue biopsies would be approximately 1 gram.

Should the Clinical Center applications propose potential analyses for the collected biospecimens?

Clinical Center applicants have the option but are not required to propose research questions and/or potential biochemical analyses to be conducted on the specified biospecimens. Applicants responding to the Chemical Analysis sites RFA will describe the appropriate analyses.

The required Statistical Analysis Plan must include the statistical methods for each specific aim, including the sample size and power calculations and plans for the primary and secondary analyses. How should Clinical Centers determine sample size? Because the overarching goal of MoTrPAC is to characterize the molecular map of signals produced by physical activity, and not to answer specific questions about those molecular signals, the statistical analyses will likely involve those aligned with high throughput bioinformatics. Are the Clinical Centers expected to have this expertise or will that expertise reside in the Chemical Analysis Centers?

Applicants should justify the proposed sample size based upon their best estimate in relation to the response to physical activity, rather than in relation to specific molecular transducers of physical activity. Keeping in mind the expected sample size indicated in the RFA, the choice of which physiologic indicator to use can be determined with justification by the applicant. Also, applicants should justify the proposed sample size based upon practical aspects (likely center-specific) of the study design. If applicants can propose an appropriate sample size for the overall clinical project, this would be enormously helpful. Considerations for the final sample size and design of the overall clinical study will be made during the planning phase (Phase1, year 1).

MoTrPAC Operations/Interactions with Other MoTrPAC Components

Will there be assistance with common Institutional Review Board (IRB) among institutions?

NIH will not mandate use of a single IRB approval process. It is likely that the Steering Committee will discuss this issue shortly after the Consortium forms. If common IRB approval processes are deemed to be the most efficient way forward, the NIH and the Consortium Coordinating Center will provide assistance.

Will the coordinating center take care of costs of study forms, data entry, data quality assurance, and long-term specimen storage? Will they also do the randomization programs?

Yes.

Budget

Is it acceptable to propose to reimburse participants for their involvement in the study, particularly for biospecimen collection?

Budgeting of participant remuneration for visits and collection of samples is acceptable. However, NIH does not permit payment that is coercive. Investigators will need to justify participant remuneration in the budget justification section.

The list of activities to be accomplished in year 1 (planning phase) is extensive and will likely require that at least some members of the research team be hired in year 1, but this will be limited by the budget. Can more than $100K be requested in year 1 if the expenses can be justified?

The applicant may request an appropriately justified budget above the limit set by the RFA, recognizing that only limited NIH funds are available for the first year of this study.

Why is the budget for the Pediatric/Adolescent Clinical Center less than the budget for a given Adult Clinical Center in years 2 through 6?

The considerably smaller sample size and less invasive biospecimen collection, as well as other less complicated aspects of the expected protocol, will require substantially fewer resources and personnel for the Pediatric/Adolescent Clinic Center compared with the Adult Clinical Centers.

Review

How will the issues of proven capabilities of a site for a Clinical Center be balanced against novelty and creativity of the specific study proposed by that center?

Both elements are important. The reviewers will be charged with considering all components of the application. Applicants should use their expertise and experience to propose what they believe to be the best possible study, and should demonstrate that the environment is appropriate and sufficient for the study. It is likely that each Clinical Center application will propose different specific goals for the clinical study; the final design will likely draw upon the best elements of all funded applications.

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This page last reviewed on November 24, 2015