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2-A-Day Study: Twice a Day Meals Study.

Primary Purpose

PreDiabetes

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Ad libitum meal timing
Twice a day meals
Sponsored by
Albert Einstein College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for PreDiabetes focused on measuring Caloric restriction, Fasting, intermittent fasting, isocaloric ad lib meal timing, Twice-a-day feeding, insulin, glucose metabolism, normoglycemia, hyperglycemia

Eligibility Criteria

30 Years - 70 Years (Adult, Older Adult)MaleAccepts Healthy Volunteers

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.

      • BMI 25-35 kg/m2

Exclusion Criteria:

  • Type 2 diabetes with A1C ≥6.8% or on drug treatment; Type 1 diabetes
  • Treatment with drugs known to influence glucose metabolism (diabetes medications, systemic glucocorticoids, niacin > 500 mg/day)
  • Current smoking, alcohol or drug abuse
  • Vigorous habitual physical activity (e.g., marathon runner, heavy weights trainers)
  • Subjects with symptomatic gastrointestinal disorders or intolerance (e.g., food allergies, lactose intolerance, gluten sensitivity, etc.) or other conditions requiring special diet or meal timing.
  • Subjects with serious chronic illness: severe (activity limiting) COPD, NYHA class 3 or 4 heart failure, kidney disease (eGFR<45ml/min), liver enzyme abnormalities (ALT > 2 times ULN), stroke, MI or ACS within last 6 months, cancer or HIV disease under treatment.
  • Any other disease/condition that the investigator believes may interfere with participation in the study (e.g., eating disorder).
  • Unstable weight conditions: gain or loss of > 5 pounds or 2.5% body weight in past 3 months.

Sites / Locations

  • Albert Einstein College of Medicine of Yeshiva UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Ad libitum meal timing first

Twice a day meals first

Arm Description

This arm will receive the ad libitum meal timing intervention first, followed by the twice a day feeding intervention.

This arm will receive the twice a day feeding intervention first, followed by the ad libitum meal timing intervention.

Outcomes

Primary Outcome Measures

Insulin sensitivity
insulin sensitivity as measured by the Matsuda Index

Secondary Outcome Measures

Glucose tolerance
Glucose level after oral glucose tolerance test as measured by glucose area under the curve.
Body Composition
Fat mass as estimated by bioimpedance analysis
Energy expenditure
Resting energy expenditure as estimated by indirect calorimetry
Autophagy level
Expression of levels of autophagosome marker LC3 by immunoblotting

Full Information

First Posted
January 8, 2019
Last Updated
February 7, 2023
Sponsor
Albert Einstein College of Medicine
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT03809299
Brief Title
2-A-Day Study: Twice a Day Meals Study.
Official Title
2-A-Day Study: Twice a Day Meals Study.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 20, 2019 (Actual)
Primary Completion Date
January 31, 2024 (Anticipated)
Study Completion Date
January 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Albert Einstein College of Medicine
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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. 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 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PreDiabetes
Keywords
Caloric restriction, Fasting, intermittent fasting, isocaloric ad lib meal timing, Twice-a-day feeding, insulin, glucose metabolism, normoglycemia, hyperglycemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ad libitum meal timing first
Arm Type
Other
Arm Description
This arm will receive the ad libitum meal timing intervention first, followed by the twice a day feeding intervention.
Arm Title
Twice a day meals first
Arm Type
Other
Arm Description
This arm will receive the twice a day feeding intervention first, followed by the ad libitum meal timing intervention.
Intervention Type
Other
Intervention Name(s)
Ad libitum meal timing
Intervention Description
Research participants will eat meals provided by the study throughout the day, ad libitum
Intervention Type
Other
Intervention Name(s)
Twice a day meals
Intervention Description
Research participants will eat meals provided by the study at two intervals during the day, and fast in between.
Primary Outcome Measure Information:
Title
Insulin sensitivity
Description
insulin sensitivity as measured by the Matsuda Index
Time Frame
5 weeks
Secondary Outcome Measure Information:
Title
Glucose tolerance
Description
Glucose level after oral glucose tolerance test as measured by glucose area under the curve.
Time Frame
5 weeks
Title
Body Composition
Description
Fat mass as estimated by bioimpedance analysis
Time Frame
5 weeks
Title
Energy expenditure
Description
Resting energy expenditure as estimated by indirect calorimetry
Time Frame
5 weeks
Title
Autophagy level
Description
Expression of levels of autophagosome marker LC3 by immunoblotting
Time Frame
1 week

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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. BMI 25-35 kg/m2 Exclusion Criteria: Type 2 diabetes with A1C ≥6.8% or on drug treatment; Type 1 diabetes Treatment with drugs known to influence glucose metabolism (diabetes medications, systemic glucocorticoids, niacin > 500 mg/day) Current smoking, alcohol or drug abuse Vigorous habitual physical activity (e.g., marathon runner, heavy weights trainers) Subjects with symptomatic gastrointestinal disorders or intolerance (e.g., food allergies, lactose intolerance, gluten sensitivity, etc.) or other conditions requiring special diet or meal timing. Subjects with serious chronic illness: severe (activity limiting) COPD, NYHA class 3 or 4 heart failure, kidney disease (eGFR<45ml/min), liver enzyme abnormalities (ALT > 2 times ULN), stroke, MI or ACS within last 6 months, cancer or HIV disease under treatment. Any other disease/condition that the investigator believes may interfere with participation in the study (e.g., eating disorder). Unstable weight conditions: gain or loss of > 5 pounds or 2.5% body weight in past 3 months.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jill Crandall
Phone
7184303765
Email
jill.crandall@einsteinmed.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jill Crandall, MD
Organizational Affiliation
Albert Einstein College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Albert Einstein College of Medicine of Yeshiva University
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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2-A-Day Study: Twice a Day Meals Study.

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