Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03809299 |
Other study ID # |
2018-9671 |
Secondary ID |
5P30DK020541 |
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
June 20, 2019 |
Est. completion date |
June 16, 2022 |
Study information
Verified date |
February 2024 |
Source |
Albert Einstein College of Medicine |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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
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.
1. c. To assess participant satisfaction with TAD meal restriction, using validated
instruments to evaluate hunger, satiety and well-being Aim 2: To collect preliminary
data on the effect of TAD meal restriction to inform design of an adequately powered RCT
2. a. To collect preliminary data on the effect of TAD meal restriction on glucose
tolerance, insulin sensitivity and secretion, body composition and energy expenditure
2b. To collect preliminary data on the effect of TAD meal restriction on cellular processes
related to autophagy