ITP Application Form for Sponsors of Longevity Intervention Proposals
NIA initiated the ITP to evaluate compounds or diets thought to extend longevity in mice by delaying or decelerating the aging process.
The Phase I experimental design has the following features:
- The primary endpoint is increased longevity.
- Test subjects are male and female genetically heterogeneous mice, bred as the four-way cross between CByB6F1 females and C3D2F1 males.
- Tests are conducted simultaneously at three sites: the University of Michigan, the Jackson Laboratory, and the NIA Intramural Program.
- The design compares multiple experimental agents to two control groups.
- Feeding of the test diets usually starts at 4 Months of age unless there are specific reasons for another time of initiation.
- Mice also are tested for several age-sensitive traits, such as T-cell subsets, humoral immunity, changes in hormone levels, and spontaneous activity.
- Agents that show promise in the initial screen are considered for the Phase II testing, a follow-up lifespan studies that includes multiple age-sensitive traits and detailed pathology.
- Group size is sufficient to detect 11 percent change in longevity at 80 percent power and 13 percent change at 90 percent power.
- All findings—positive or negative—are submitted for publication.
Request for Proposals
NIA seeks proposals for specific compounds or dietary agents to be included in Phase I screening. The applicant, or “sponsor”, designs and justifies the specific treatment protocol and collaborates in evaluating the results and preparing them for publication. Sponsors can be individuals, nonprofit or academic groups, or commercial concerns. NIA is responsible for the costs of the testing through the grants to the three testing sites.
This application form is for sponsors who wish to suggest specific interventions for consideration by the ITP. Individuals or groups who wish to propose more than one intervention for consideration are encouraged, but should use separate application forms for each proposed intervention.
Applications—in Microsoft Word format—should be sent to Dr. Francesca Macchiarini. Questions about the program or the application process should be submitted to Dr. Francesca Macchiarini (Francesca.Macchiarini@nih.gov).
Potential sponsors should submit a proposal in Microsoft Word format. The application should address the following, in this order:
Title of Proposal
The title of the proposal is typically the name of the substance or dietary formulation being tested (e.g., “Selenium-Conjugated Carboxyfullerenes”).
Applicant's Contact Information
This information includes the name, institutional address, telephone, fax, and e-mail of the individual submitting the application.
This section should describe concisely the reason why the compound or dietary formulation deserves to be evaluated for potential effects on longevity and aging. The rationale may include:
- Theoretical ideas
- Pilot data in mice, invertebrates, or humans if available
- Other justification
If this section includes unpublished data, include enough information (i.e., figures, tables, protocols) to permit its evaluation. If the section includes published data, include similar information and a reference citation to the publication(s) from which the data are derived.
There is no length limit, but it is recommended that the background section be no longer than five pages (including figures and tables).
Suggested Treatment Protocol
This section should provide a detailed description of the diet or compound being tested and the rationale for the protocol proposed. This information is necessary in order to develop a final testing protocol. The following should be addressed:
- Can the substance be given in food or water? What dose should be used? How stable is the compound when incorporated into food? Should the preparations be protected from light or heat?
- What is the suggested source of the test materials? If available commercially, which supplier(s) are suggested and why? How expensive would the treatment be (in dollars per mouse per year of treatment)?
- What is the best way to monitor test animals to ensure intake of the compounds produces the expected physiological or pharmacological effects in this animal model? Will this require blood tests or skin samples, or will it require that some of the mice be sacrificed to obtain internal tissues? If a blood test is required, how much blood is needed? At what age, or at what time after treatment initiation, should the test be performed? How expensive is the test to conduct? If the test requires specialized expertise or equipment, is this available in the sponsor's laboratory?
- Is there a reason to initiate feeding of the intervention at an age other than 4 months of age? If so, what age should the treatment be initiated? Is there a range of ages that would be acceptable?
Animal Safety Information
This section should describe what is known about potential harmful side effects the treatment might have on mice. If the applicant knows of any pilot data based on either short-term or long-term exposure of rodents or other mammals to the treatment, the application should state this and describe any harmful side effects noted in the previous study. If the applicant knows of toxicity data related to other doses of the compound or to related compounds, this should be summarized for evaluation by an institutional animal use committee.
The ITP provides all costs for animal acquisition, animal housing, testing, and statistical analysis. It also includes a limited budget for purchase, or cost-shared purchase, of test substances.
- The applicant should indicate if the compound cannot be obtained commercially or must be obtained from the applicant.
- If the compound can be purchased from commercial sources, provide a justified estimate of the cost of obtaining a sufficient supply of the compound to treat 350 mice for 3 years. A complete Phase I test requires approximately 2100 kg of food with the compound (2100 kg is the amount needed for 350 mice over a three-year period). For example, if a compound will be fed at 300 ppm in the food, i.e. 300 mg/Kg, the total amount of the compound needed is 300 mg/kg X 2100 kg = 630,000 mg or 630 grams.
- If the compound is not available commercially and cannot be provided to the ITP without charge, the applicant should: (1) provide a justified cost estimate of a sufficient supply of the compound to treat 350 mice for 3 years (enough to prepare 2100 kg over 3 years), and (2) state the proportion of the cost the ITP is expected to provide.
Statement of Understanding
The application should include the following statement of understanding:
In submitting this proposal, I agree to the following:
- I understand all information presented in the proposal can be freely shared with members of the ITP Steering Committee and Access Panel during their evaluation of proposals, but will otherwise be considered confidential.
- If my proposal, or a modification of it (such as altered dosage or frequency of administration), is accepted for inclusion in a research protocol, I will be asked to help evaluate the data and to prepare the data for written and oral publications, on each of which I will be offered coauthorship. I understand the ITP intends to submit the results of all ITP-supported studies—regardless if they produce data showing positive or negative effects on health status in mice—for publication.
- I understand data generated by ITP-supported experiments using the compound/diet proposed will be made publicly available and can be used in applications for further research support by anyone. I also will be free to use ITP-generated data in the context of applications for research support or for any other purpose.
- Include only if applicable: The compound/diet proposed makes use of materials that are not yet freely available and whose production depends on proprietary or unpublished methods. If my application is approved for incorporation in the ITP, a mutually acceptable Materials Transfer Agreement that would permit me to provide the ITP with the compound(s) needed for the experimentation will be developed with the institutions involved in this program.
How To Apply
Submit proposals as a Word document via email, and include an NIH BioSketch or CV (Word or .PDF), to Dr. Francesca Macchiarini (Francesca.Macchiarini@nih.gov).
The next deadline is February 28, 2019, 5:00 PM Eastern time.
For more information, contact:
Francesa Macchiarini, Ph.D.
National Institute on Aging
7201 Wisconsin Ave., GW 3C300
Bethesda, MD 20892
Email Dr. Francesca Macchiarini