Key Dates

Related Announcements

• April 24, 2024 – NIH Pathway to Independence Award (Parent K99/R00 - Independent Clinical Trial Not Allowed). See PA-24-194.
• February 09, 2024 – The NCI Transition Career Development Award (K22 Independent Clinical Trial Optional). See PAR-24-117.
• January 18, 2024 – Modular R01s in Cancer Control and Population Sciences (R01 Clinical Trial Optional). See PAR-24-122.
• December 20, 2023 – Stephen I. Katz Early-Stage Investigator Research Project Grant (R01 Clinical Trial Not Allowed). See PAR-24-075.
• December 20, 2023 – Notice of Special Interest: National Cancer Institute Supports Applications for the Mentored Research Scientist Development Awards (K01) Within the Mission of the Division of Cancer Prevention. See NOT-CA-24-023. 
• December 20, 2023 – Notice of Special Interest: National Cancer Institute Supports Applications for the Mentored Research Scientist Development Awards (K01) Within the Mission of the Division of Cancer Control and Population Sciences. See NOT-CA-24-022.
• December 15, 2023 – Cancer Prevention and Control Clinical Trials Grant Program (R01 Clinical Trial Required). See PAR-24-072.
• July 14, 2022 – NCI Clinical and Translational Exploratory/Developmental Studies (R21 Clinical Trial Optional). See PAR-22-216.
• June 23, 2022 – Cancer Prevention and Control Clinical Trials Planning Grant Program (R34 Clinical Trials Optional). See PAR-22-173.
• June 23, 2022 – Cancer Prevention and Control Clinical Trials Planning Grant Program (U34 Clinical Trials Optional). See PAR-22-174. 
• October 12, 2021 – Exploratory Grants in Cancer Control (R21 Clinical Trial Optional). See PAR-21-341.
• September 10, 2021 – NCI Mentored Clinical Scientist Research Career Development Award to Promote Diversity (K08 Independent Clinical Trial Not Allowed). See PAR-21-300.
• May 05, 2020 – NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See PA-20-185.

Issued by

National Cancer Institute (NCI)

Purpose

The purpose of this notice of special interest (NOSI) is to promote studies examining the sustainability of TRE and the potential impact it may have on obesity and cancer across the cancer continuum. Questions can be considered in various populations/contexts and study designs. Mechanistic and epidemiological studies and clinical trials are encouraged where warranted to address one or more of the scientific question(s) above. A project can also incorporate preclinical investigations to help evaluate mechanistic endpoints. Applications that include collaborators from fields outside of cancer research will be given special programmatic consideration. Findings from these studies could provide evidence to help inform researchers and healthcare providers regarding the feasibility and best approach(es) to implementing TRE dietary strategy.

Background

Metabolic syndrome consists of a constellation of clinical factors associated with an increased risk of cardiovascular disease, type 2 diabetes and cancer. A systematic review and meta-analysis of studies evaluating metabolic syndrome spanning 43 articles with 38,940 cases of cancer found that in men, metabolic syndrome was significantly associated with liver, colorectal, and bladder cancer, while in women it was significantly associated with endometrial, pancreatic, postmenopausal breast, and colorectal cancer. Animal studies have demonstrated that altering the eating window through intermittent fasting (IF), whether fasting for a select number of days each week or month or some period of time each day, has metabolic benefits. These benefits, which may or may not be associated with weight loss, often lead to improvements in glucose tolerance and insulin sensitivity. In humans, restricting the eating window to a set time period each day – or time-restricted eating (TRE) – allows for the continuation of dietary pattern preferences. Its flexibility may have greater compliance over the long-term compared to more involved approaches such as those requiring a complete change in diet. It may also require less cognitive effort and facilitate dietary satisfaction, adherence, and long-term weight loss maintenance. However, human studies thus far conducted on TRE are less mature and less consistent in their findings than animal studies. 
 

TRE is a dietary strategy whose primary likelihood of success is in metabolic improvement. TRE involves an ad libitum eating window of 3-12 hours/day. A unique feature of TRE is that it allows continuation of one’s usual diet without restriction. The ability to adhere to TRE long-term and its impact on health is not well known. For practical, real-world considerations, there is an important gap in addressing adherence to TRE >12 months as part of the initial study design, though a few studies suggest long-term adherence to TRE is feasible. Nineteen participants who completed a 12-week TRE study were contacted approximately 16 months after study completion to determine their elective continuation of TRE. Almost two-thirds (~63%) continued some form of TRE. Studies of religious fasting among Seventh Day Adventists and secondary analysis using the Women's Healthy Eating and Living (WHEL) study among breast cancer survivors also suggest that some individuals are able to adhere to TRE for years. 
 

On the other hand, it is important to consider that TRE may not be the best dietary approach for everyone. Many people initiate a diet with the primary goal of losing weight, with metabolic improvement as a secondary benefit. TRE does not lead to weight loss among all individuals, especially if the individual consumes as many or more calories than they did before initiating TRE. For individuals whose primary purpose is weight loss, they may not adhere to TRE in the long term.
 

In 2020, the National Cancer Institute challenged scientists to determine whether IF, including TRE, improved metabolic health with Provocative Question (PQ) 2: How does intermittent fasting affect cancer incidence, treatment response, or outcome? As stated then, the intent of the PQ was to “better understand the effects of IF in humans on cancer risk factors, cancer incidence, treatment response, or cancer related outcomes (such as disease recurrence or survival). There are several additional questions related to TRE that need to be addressed as they relate to cancer.

Research Objectives

There are important unanswered questions as to whether adhering to a TRE dietary strategy will improve metabolic outcomes and lower cancer risk, improve cancer treatment response and outcomes, and/or improve other obesity and cancer-related outcomes, including among long-term cancer survivors. Intermediate markers and health outcomes such as insulin sensitivity and inflammation can be used as endpoints given the importance of such factors in mediating obesity and cancer-related outcomes. Several specific questions need to be addressed in this space, including:

• Is long-term adherence to TRE more sustainable than long-term (> 1 year) adherence to a caloric restriction diet or other dietary strategy?
• Is metabolic dysfunction improved with TRE in the absence of weight loss?
• Does the 1) timing or 2) length of the eating window matter regarding benefit? Is there objective metabolic evidence that allowing an individual to choose their own time of day and length of eating window is better than prescribing a specific time and length each day that one eats?
• Do certain subpopulations benefit from TRE more or less than others (e.g., differences by sex, race/ethnicity, age, healthy vs. clinical populations)?
• Is sleep health improved by following TRE?
• What granularity of data is needed to best capture adherence and understand the impact of TRE on health outcomes?

Application and Submission Information

This notice applies to due dates on or after September 26, 2024, and subsequent receipt dates through May 08, 2027.

Submit applications for this initiative using one of the following notice of funding opportunity (NOFO) or any reissues of these announcements through the expiration date of this notice.

In addition to the NOFOs listed in the above Table, please also consider the following notices of special interest (NOSIs) that allow submissions through Parent K01 NOFOs:

• December 20, 2023 – Notice of Special Interest: National Cancer Institute Supports Applications for the Mentored Research Scientist Development Awards (K01) Within the Mission of the Division of Cancer Prevention. See NOT-CA-24-023
• December 20, 2023 – Notice of Special Interest: National Cancer Institute Supports Applications for the Mentored Research Scientist Development Awards (K01) Within the Mission of the Division of Cancer Control and Population Sciences. See NOT-CA-24-022

All instructions in the How to Apply - Application Guide and the notice of funding opportunity used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-CA-24-073” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:

Scientific/Research Contact(s)
 

Edward Sauter, MD, PhD
National Cancer Institute (NCI)
Telephone: 240-276-7657
Email: edward.sauter@nih.gov

Tanya Agurs-Collins, PhD, RD
National Cancer Institute (NCI)
Telephone: 240-276-6956
Email: collinsta@mail.nih.gov

Peer Review Contact(s) 
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).
 

Financial/Grants Management Contact(s)
 

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: wolfreyc@mail.nih.gov