Time-Restricted Eating for Type II Diabetes: TRE-T2D

Study Overview
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Brief Summary
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This is a randomized clinical trial to assess the feasibility and efficacy of time-restricted eating (TRE) to improve glucose regulation and cardiovascular health of participants with type 2 diabetes mellitus (T2DM). Participants will be randomized into 2 groups: 1) standard of care (SOC), in which they will continue to follow their physician's treatment plan, or 2) SOC and TRE (8-10 hours eating window).

Detailed Description
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The intervention will last for 12 weeks with a follow-up assessment at 6 months. This study will deliver the intervention, monitor participant health for safety, and promote compliance through clinic visits, virtual consultations, and an innovative combination of sensors, including continuous glucose monitors, actiwatches (to assess activity and sleep patterns), and the myCircadianClock smartphone app (to capture food, beverage, and medicine intake in real time). In-depth clinical and analytical measurements will be conducted at baseline and at the end of the intervention. We hypothesize that TRE will result in improved glucose levels (assessed via Hemoglobin A1c, the gold standard in clinical trials of T2D) and improved cardiovascular health (assessed via LDL or bad Cholesterol and Triglycerides). We will also be examining long-term adherence to TRE and improvements in quality of life. The proposed study will be the first adequately powered, randomized trial of TRE in patients with T2DM on background medical therapy. It is founded on a strong scientific premise and utilizes rigorous study design, state-of-the-art methods for analyzing outcomes, and an innovative approach for engaging and sustaining participation. Successful completion of this clinical trial will lay the scientific foundation and establish safety parameters for widespread implementation of TRE in patients with T2DM.

Official Title
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Feasibility and Efficacy of Time-Restricted Eating in Diabetes Management

Conditions
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Diabetes Mellitus, Type 2, Time Restricted Feeding, Diabetes type2

Intervention / Treatment
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* Behavioral: Time-Restricted Eating
* Behavioral: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-70 years old Patients with T2DM with A1c between 6.5 and 9.0 % and on stable doses of medications who are weight-bearing and self-ambulatory. Own a smartphone (Apple iOS or Android OS) Baseline eating period ≥12 hours/day and sufficient logging on the mCC app. Women of childbearing age will be given a pregnancy test on study enrollment and asked to use contraception throughout the study. Post-menopausal and women on hormone replacement therapy will be included. Estimated Glomerular Filtration Rate (EGFR) > 50 If participants are on cardiovascular medications (HMG CoA reductase inhibitors (statins), other lipid-modifying drugs, anti-hypertensives) no dose adjustments will be allowed during the study period Patients on stable doses of GLP-1 receptor agonists will be included. Exclusion Criteria: Participants with Type1DM and T2DM who are taking insulin, sulfonylureas, or have an HbA1c > 9 %. BMI > 40 kg/m2 Systolic BP greater than 160 mmHg and/or Diastolic BP greater than 110 mmHg (with or without treatment/medication) LDL cholesterol greater than 200 mg/dL Triglycerides greater than 500 mg/dL Active tobacco or illicit drug use Pregnant or breastfeeding women. Currently enrolled in a weight-loss or weight-management program, Currently on a special or prescribed diet for other reasons (e.g., Celiac disease), Currently taking any medication that is meant for weight loss, or has known effect on appetite suppression, History of eating disorder(s). History of surgical intervention for weight management (e) active eating disorder. Chronic kidney disease with an eGFR calculated based on the Modification of Diet in Renal Disease (MDRD) equation <50mL/min/1.73m2 Treatment for active inflammatory and/or rheumatologic disease and cancer. A major adverse cardiovascular event within the past 6 months such as acute coronary syndrome (ACS), percutaneous coronary intervention, coronary artery bypass graft surgery, hospitalization for congestive heart failure, stroke/transient ischemic attack (TIA). History of Uncontrolled arrhythmia (i.e., rate-controlled atrial fibrillation/atrial flutter are not exclusion criteria) Liver cirrhosis and/or significant alterations in liver function History of (a) thyroid disease requiring dose titration of thyroid replacement medication(s) within the past 3 months (i.e., hypothyroidism on a stable dose of thyroid replacement therapy is not an exclusion) Known inflammatory and/or rheumatologic disease. Shift workers with variable (e.g., nocturnal) hours. Caregivers for dependents requiring frequent nocturnal care/sleep interruptions. More than one trip planned to travel to a time zone with greater than a 3-hour difference during study period. History of major adverse cardiovascular events within the past 1 year (acute coronary syndrome (ACS), percutaneous coronary intervention, coronary artery bypass graft surgery, hospitalization for congestive heart failure, stroke/transient ischemic attack (TIA)). History of thyroid disease requiring dose titration of thyroid replacement medication(s) within the past 3 months (i.e., hypothyroidism on a stable dose of thyroid replacement therapy is not an exclusion). History of adrenal disease. History of malignancy undergoing active treatment, except non-melanoma skin cancer. Known history of type I diabetes. History of stage 4 or 5 chronic kidney disease or requiring dialysis. History of HIV/AIDS. Uncontrolled psychiatric disorder (including history of hospitalization for psychiatric illness).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Standard of Care<br>The participants in this arm will receive the standard health and nutritional wellness guidelines and will be required to log food entries through the use of a smartphone app. | Behavioral: Standard of Care<br>* Participants in the Standard of Care group will continue to follow their physician's treatment plan for type II diabetes mellitus.<br>* Other names: Control group;|
| Experimental: Time-Restricted Eating<br>The participants in this arm will limit the number of hours they eat in day to a 8-10-hour window and will also receive the standard health and nutritional wellness guidelines. They will also be required to log food entries through the use of a smartphone app. | Behavioral: Time-Restricted Eating<br>* Participants in the TRE group with continue to follow their physicians treatment plan for type II diabetes mellitus and consume all of their food within an 8-10 hour eating window.<br>* Other names: Time Restricted Feeding;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic regulation assessed by HbA1c | Change in blood glucose assessed via hemoglobin A1c. | Baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic regulation assessed by Continuous Glucose Monitor (CGM) | Change in glycemic regulation as assessed by CGM from interstitial glucose with outcomes including time in range, glycemic variability, and mean glucose. | Baseline and 3 months | 
| Fasting plasma glucose (mg/dL) | Change in glycemic regulation as assessed fasting plasma glucose (mg/dL). | Baseline and 3 months | 
| Fasting plasma insulin (mIU/L) | Change in glycemic regulation as assessed changes in fasting plasma insulin (mIU/L). | Baseline and 3 months | 
| HOMA-IR | Change in glycemic regulation as assessed by HOMA-IR. | Baseline and 3 months | 
| LDL Particle Number (nmol/L) | Changes in atherogenic lipids assessed via LDL Particle Number (nmol/L) via NMR Lipoproteinprofile. | Baseline and 3 months | 
| Non-HDL Cholesterol (mg/dL) | Changes in atherogenic lipids assessed via Non-HDL Cholesterol (mg/dL). | Baseline and 3 months | 
| Triglycerides (mg/dL) | Changes in atherogenic lipids assessed via Triglycerides (mg/dL). | Baseline and 3 months | 
| Apolipoprotein B (ApoB) | Changes in atherogenic lipids assessed via ApoB (mg/dL). | Baseline and 3 months | 
| Quality of life Assessment via Short Form-36 Questionnaire (SF-36) | Changes in quality of life as assessed by the SF-36 questionnaire. | Baseline and 3 months |