Condition or disease | Intervention/treatment | Phase |
---|---|---|
PreDiabetes | Other: Ad libitum meal timing Other: Twice a day meals | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 25 participants |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 2-A-Day Study: Twice a Day Meals Study. |
Actual Study Start Date : | June 20, 2019 |
Estimated Primary Completion Date : | June 1, 2021 |
Estimated Study Completion Date : | June 1, 2021 |
Arm | Intervention/treatment |
---|---|
Ad libitum meal timing first
This arm will receive the ad libitum meal timing intervention first, followed by the twice a day feeding intervention.
|
Other: Ad libitum meal timing
Research participants will eat meals provided by the study throughout the day, ad libitum
Other: Twice a day meals Research participants will eat meals provided by the study at two intervals during the day, and fast in between.
|
Twice a day meals first
This arm will receive the twice a day feeding intervention first, followed by the ad libitum meal timing intervention.
|
Other: Ad libitum meal timing
Research participants will eat meals provided by the study throughout the day, ad libitum
Other: Twice a day meals Research participants will eat meals provided by the study at two intervals during the day, and fast in between.
|
Ages Eligible for Study: | 30 Years to 70 Years (Adult, Older Adult) |
Sexes Eligible for Study: | Male |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
● Men, age 30-70 years. In this preliminary study, recruitment is limited to men because data from the relevant animal studies showed marked sexual dimorphism, with more pronounced metabolic effects in males. Future studies will include both males and females.
IFG or IGT based on 75g OGTT (fasting plasma glucose 100 -125 mg/dl and/or 2-hr glucose between 140 - 199 mg/dl); Or diabetes (FPG > 126 mg/dl or 2 hr glucose > 200 mg/dl) not on treatment and with HbA1c < 6.8% can also be enrolled.
Exclusion Criteria:
Contact: Jill Crandall | 7184303765 | jill.crandall@einstein.yu.edu | |
Contact: Erika Brutsaert | 7188397961 | erika.brutsaert@einstein.yu.edu |
United States, New York | |
Albert Einstein College of Medicine of Yeshiva University | Recruiting |
Bronx, New York, United States, 10461 |
Principal Investigator: | Jill Crandall, MD | Albert Einstein College of Medicine |
Tracking Information | |||||||||
---|---|---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | January 8, 2019 | ||||||||
First Posted Date ICMJE | January 18, 2019 | ||||||||
Last Update Posted Date | October 22, 2020 | ||||||||
Actual Study Start Date ICMJE | June 20, 2019 | ||||||||
Estimated Primary Completion Date | June 1, 2021 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Insulin sensitivity [ Time Frame: 5 weeks ] insulin sensitivity as measured by the Matsuda Index
|
||||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
|
||||||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | 2-A-Day Study: Twice a Day Meals Study. | ||||||||
Official Title ICMJE | 2-A-Day Study: Twice a Day Meals Study. | ||||||||
Brief Summary | Caloric restriction increases lifespan and/or healthspan across multiple species. However implementation of long-term CR in humans is problematic and unacceptable to many individuals. As a result, intermittent fasting models have been developed to improve adherence. Such models have been shown to improve blood pressure, insulin sensitivity, decrease hepatic fat content and body weight. Investigators established an isocaloric twice-a-day (ITAD) feeding plan in mice, wherein test mice were acclimatized to consume over two hour periods (8-10am and 5-7pm), the same amount of food as ad-libitum mice. This intervention prevented obesity and age-associated type 2 diabetes via system-wide activation of autophagy. The investigators will perform further studies of the same feeding model in humans in a randomized crossover design. The objective is to test the hypothesis that restricting eating periods to twice a day (TAD), when compared to isocaloric ad lib meal timing (ALMT), will have beneficial effects on glucose metabolism, body composition, energy expenditure and autophagy in human subjects at risk for diabetes | ||||||||
Detailed Description |
Caloric restriction (CR) increases lifespan and/or healthspan across multiple species including non-human primates. However, implementation of long-term CR in humans is problematic and unacceptable to many individuals. Further, since CR leads to loss of muscle mass in mice, it is likely that its implementation as a restorative strategy during aging may exacerbate age-associated muscle loss. As a result, intermittent fasting models, e.g., alternate-day fasting, alternate day-modified fasting, the 5:2 diet, and the more recently elucidated early time-restricted feeding (eTRF)3 were developed as alternative strategies to improve adherence. Intermittent fasting increases glucose clearance/improves insulin sensitivity, decreases hepatic fat content, lowers blood pressure and body weight by varying degrees (at least when calories were unmatched). Despite these metabolic advantages, these approaches have also shown poor adherence in humans. For instance, alternate-day fasted subjects remained hungry on the fast days, which led to the conclusion that this approach cannot be continued for extended periods of time, and that adding one small meal on the fasting day may make this model more acceptable. Accordingly, in alternate day-modified fasting, fasted days (25% caloric intake) alternated with feasting days (125% calories), which improved compliance although dropout rates remained relatively high (38%) when compared to control group (26%). In addition, this feeding approach was not found to be superior to daily caloric restricted controls in terms of adherence, weight loss or cardiovascular benefits. More recently, eTRF wherein men with prediabetes were subjected to a 6-hr feeding interval with dinner before 1 pm displayed a number of metabolic benefits when compared to individuals on a 12-hr feeding time-frame. Nevertheless, due to vocational or societal factors, it is plausible that a vast majority of individuals may not be able to adhere to a regimen requiring the consumption of three meals within the first 6 hr of the diurnal cycle. In the attempt to offset compliance-related issues and to pursue a simpler approach, investigators established an isocaloric twice-a-day (ITAD) feeding plan in mice, wherein test mice are acclimatized to consume over two 2hr-periods (8:00-10:00am and 5:00-7:00pm) the same amount of food as ad libitum-fed mice. This would effectively translate to a breakfast and dinner (two meals) in humans. It has been shown that two periods of food restriction per day in mice prevents obesity and age-associated type 2 diabetes via system-wide activation of autophagy. This study is to determine if twice-a-day feeding will restore normoglycemia and promote metabolic correction in older men with prediabetes. Autophagy is a lysosomal degradative pathway that plays key roles in maintaining "clean" cells. It is well-established that basal autophagy levels begin to decline progressively in aged organisms. Maintaining higher autophagy levels improves organ function and stress response. For instance, liver-specific overexpression of autophagy genes protects against diet-induced obesity and tumor necrosis factor-mediated acute hepatotoxicity. In the investigators' studies with ITAD feeding in mice, blocking autophagy in distinct tissues resulted in loss of the metabolic benefits from this feeding strategy. Consequently, it is propose that establishing ITAD feeding in humans will yield a cost-effective, practical and immediately translatable strategy to prolong health-span by preventing diabetes and sarcopenia as well as the vast number of secondary diseases caused by sustained hyperglycemia. This study will investigate the feasibility of a TAD eating regimen and collect preliminary data to inform a larger-scale and more definitive trial. Specific Aims: Aim 1: To assess the feasibility of implementing a structured TAD eating regimen using study-provided meals 1a. To design meal plans that are isocaloric with habitual intake and intended to maintain weight and to develop methods to prepare, package and deliver the meals. 1b. To develop and evaluate methods to enhance and monitor participant adherence to TAD eating; this will include patient logs, photo records of food intake and continuous (participant blinded) glucose monitoring.
2b. To collect preliminary data on the effect of TAD meal restriction on cellular processes related to autophagy |
||||||||
Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Not Applicable | ||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||||||
Condition ICMJE | PreDiabetes | ||||||||
Intervention ICMJE |
|
||||||||
Study Arms ICMJE |
|
||||||||
Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||||
Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
25 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | June 1, 2021 | ||||||||
Estimated Primary Completion Date | June 1, 2021 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
||||||||
Sex/Gender ICMJE |
|
||||||||
Ages ICMJE | 30 Years to 70 Years (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | Yes | ||||||||
Contacts ICMJE |
|
||||||||
Listed Location Countries ICMJE | United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03809299 | ||||||||
Other Study ID Numbers ICMJE | 2018-9671 5P30DK020541 ( U.S. NIH Grant/Contract ) |
||||||||
Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
|
||||||||
IPD Sharing Statement ICMJE |
|
||||||||
Responsible Party | Jill Crandall, Albert Einstein College of Medicine | ||||||||
Study Sponsor ICMJE | Albert Einstein College of Medicine | ||||||||
Collaborators ICMJE | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | ||||||||
Investigators ICMJE |
|
||||||||
PRS Account | Albert Einstein College of Medicine | ||||||||
Verification Date | October 2020 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |