Effect of Time-Restricted Feeding on 24-hour Glycemic Control, Blood Pressure, and Cardiovascular Disease Risk Factors

Study Overview
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Brief Summary
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One in three American adults have prediabetes, and up to 70% of adults with prediabetes eventually develop type 2 diabetes. With the high cost of treating diabetes, cost-effective approaches are needed to reduce the incidence of diabetes. One new strategy may be to change when people eat. Studies in rodents suggest that a form of intermittent fasting that limits eating to a short time period each day and involves fasting for the rest of the day (time-restricted feeding; TRF) improves blood sugar control and cardiovascular health. Preliminary studies suggest that TRF also improves blood sugar, weight loss, and cardiovascular health in humans. This study will be the first full-scale, controlled feeding trial to determine whether TRF can improve 24-hour blood sugar control, 24-hour blood pressure, and cardiovascular disease risk factors even when food intake is matched to the control group. This clinical trial will also determine whether the benefits of TRF depend on the time of day that people eat. Participants will be assigned to one of three groups: (1) 'Early TRF' (eat between  8 am-3 pm), (2) 'Mid-day TRF' (eat between  1 pm - 8 pm), or (3) Control Schedule ( 8 am - 8 pm) for 10 weeks. All food will be provided and matched between groups.

Official Title
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Effect of Time-Restricted Feeding on 24-hour Glycemic Control, Blood Pressure, and Cardiovascular Disease Risk Factors in Adults With Prediabetes

Conditions
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PreDiabetes

Intervention / Treatment
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* Behavioral: Early Time-Restricted Feeding
* Behavioral: Mid-day Time-Restricted Feeding
* Behavioral: Control Schedule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 30-65 years old Prediabetic as determined by HbA1c between 5.7-6.4% or fasting glucose between 100-125 mg/dl BMI between 27-43 kg/m^2 Wake up at a regular time between 5-8 am Exclusion Criteria: On diabetes medication or any medication known to affect glucose or blood pressure Change in the dosage of a chronic medication within the past 3 months Have a clinically significant laboratory abnormality (e.g., abnormal hemoglobin levels) Significant gastrointestinal disease, major gastrointestinal surgery, or gallstones Significant cardiovascular, renal, cardiac, liver, lung, adrenal, or nervous system disease that might compromise the participant's safety or data validity Evidence of cancer within the last 5 years Pregnant or breastfeeding Diagnosed psychiatric conditions Sleep disorder, circadian disorder, or regularly sleep less than 6 hours per night Currently, perform overnight shift work Regularly eat within a <9-hour period each day Lost or gained more than 3 kg of weight in the past 3 months

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 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
Interventional Model Description: Randomization will be stratified by fasting insulin. Within the lowest insulin strata, randomization will be further stratified by biological sex.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Time-Restricted Feeding<br> | Behavioral: Early Time-Restricted Feeding<br>* Eat between 8 am - 3 pm (or 7 am - 2 pm, if an early riser)<br>* Other names: Early TRF;|
| Experimental: Mid-day Time-Restricted Feeding<br> | Behavioral: Mid-day Time-Restricted Feeding<br>* Eat between 1 pm - 8 pm (or 12 pm - 7 pm, if an early riser)<br>* Other names: Mid-day TRF;|
| Placebo Comparator: Control Schedule<br> | Behavioral: Control Schedule<br>* Eat between 8 am - 8 pm (or 7 am - 7 pm, if an early riser)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean 24-hour glucose levels | Mean 24-hour glucose levels (mg/dl) | 10 weeks | 
| Mean 24-hour insulin levels | Mean 24-hour insulin levels (mU/l) | 10 weeks | 
| Mean 24-hour C-peptide levels | Mean 24-hour C-peptide levels (pmol/l). This is also a proxy for total 24-hour insulin secretion. | 10 weeks | 
| Insulin sensitivity | Mean value of insulin sensitivity (dl/kg/min/μU/ml) across the three identical meal tolerance tests, as measured by the Oral Minimal Model | 10 weeks | 
| Beta-cell responsivity index (a measure of beta-cell function) | Mean value of beta-cell responsivity across the three identical meal tolerance tests, as measured by the Oral Minimal Model | 10 weeks | 
| Glucose AUCs | Glucose area-under-the-curve (mg/dl x hr) during each of three identical meal tolerance tests within a 24-hour period | 10 weeks | 
| Insulin AUC | Insulin area-under-the-curve (mU/l x hr) during each of three identical meal tolerance tests within a 24-hour period | 10 weeks | 
| C-peptide AUC | C-peptide area-under-the-curve (pmol/l x hr) during each of three identical meal tolerance tests within a 24-hour period | 10 weeks | 
| Peak glucose and mean amplitude of glycemic excursions (MAGE) glucose values | mg/dl | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean 24-hour systolic and diastolic blood pressure | mmHg | 10 weeks | 
| Daily maximum value, minimum value, and amplitude of systolic and diastolic blood pressure | mmHg | 10 weeks | 
| Percentage of individuals with non-dipping blood pressure phenotypes |  | 10 weeks | 
| Heart Rate | beats per minute | 10 weeks | 
| Lipids | Total cholesterol (mg/dl), LDL cholesterol (mg/dl), HDL cholesterol (mg/dl), and triglycerides (mg/dl) | 10 weeks | 
| High Sensitivity C-Reactive Protein (hs-CRP) | mg/l | 10 weeks | 
| Cortisol | μg/dl | 10 weeks | 
| 8-isoprostane | pg/ml | 10 weeks | 
| Inflammatory biomarkers | TNF-alpha, IL-1beta, IL-4, IL-6, IL-10 (in pg/ml) | 10 weeks |