Time Restricted Eating on Cancer Risk

Study Overview
=================
Brief Summary
-----------------
Participants will be randomly assigned to either the time restricted feeding group with a daily eating period of 8 hours or the control group with a daily eating period of greater than or equal to 12 hours. There are 2 in-person study visits to have blood, urine and vital signs collected and 8 remote or phone visits with a psychologist or dietician to assist with the eating schedule. The study will take last 3 1/2 months.

Official Title
-----------------
The Effects of Time Restricted Feeding on AGE-RAGE Signaling in Women at High Risk for Breast Cancer

Conditions
-----------------
Pre-diabetes, Breast Cancer, Time Restricted Feeding

Intervention / Treatment
-----------------
* Behavioral: Time restricted feeding
* Behavioral: Control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 40 and ≤ 67; Postmenopausal women (no menstrual periods in the preceding 12 or more months) with pre-diabetes (A1C 5.7-6.4% and/or fasting glucose 100-125 mg/dL). A1c lab and/or fasting glucose criteria will need to be met within 12 months of signing consent form, can be obtained from prior lab result or study prescreening testing; Own a smart phone with internet connection and capable of receiving and sending text messages and taking photographs; Exclusion Criteria: Tobacco use (current or within last 2 years); Active malignancy or history of cancer; History of known liver disease (by serology: aspartate aminotransferase or alanine aminotransferase ≥ 3 times above upper limit of normal determined by lab review, imaging or biopsy: determined by patient history); History of kidney disease (patient history and/or estimated glomerular filtration rate less than 45 mL/min/1.73m²); History of diabetes mellitus: History of cardiovascular disease (MI, CHF); Current prescription medication use for diabetes; Medication affecting glucose metabolism or appetite or immunosuppression; Dietary restrictions: currently following vegetarian or vegan dietary pattern; Currently following intermittent fasting or time restricted feeding pattern or use in the last 3 months; Night shift worker (work schedule does not involve any period of work from 10 PM to 5 AM either on a regular or rotating basis); History of weight loss >5% in the last 3 months; History of weight loss surgery. BMI≥40 kg/m² exclusion; After informed consent and run in period: Insufficient documented food photography/annotated entries (does not log at least two entries a day for 10 of 14 days) during run in period will be excluded from randomization in to the intervention period.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 67 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Time restricted feeding<br>daily eating period of 8 hours, before 8 PM | Behavioral: Time restricted feeding<br>* Participants will eat all food during a self selected 8 hour eating window prior to 8:00 PM.<br>|
| Active Comparator: Control<br>daily eating period ≥ 12 hours | Behavioral: Control<br>* Participants will have a daily eating period equal to or greater than 12 hours.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Advanced Glycation End Products (AGE) as assessed by plasma | Estimated mean levels within the intervention and the control groups of the study. Effect size will be estimated via 95% confidence intervals within and between groups. | Visit 1 and Visit 2 approximately 12 weeks | 
| Change in sRAGE(soluble receptor for AGE) levels | Estimated mean levels within the intervention and the control groups of the study. Effect size will estimated via 95% confidence intervals within and between groups. .The intervention and control groups of AGE and sRAGE levels will be used to determined AGE by sRAGE ratio | Visit 1 and Visit 2, approximately 12 weeks | 
| Assess feasibility and adherence to time period of eating recommendations in both study groups. | Proportion of days that time period of eating was followed. | Visit 1 and Visit 2, approximately 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting insulin-like growth factor-1 (IGF-1) levels | Estimated mean levels within the intervention and the control groups of the study. Effect size will be estimated via 95% confidence intervals within and between groups. | Visit and Visit 2, approximately 12 weeks | 
| Change in Fasting insulin levels | Estimated mean levels within the intervention and the control groups of the study. Effect size will be estimated via 95% confidence intervals within and between groups. | Visit 1 and Visit 2, approximately 12 weeks | 
| Difference in Glasgow Prognostic Scoring System | The Glasgow Prognostic Score (GPS) reflects systemic inflammatory process. Difference within groups and between groups of the cumulative inflammation-based cancer-prognostic marker. GPS is a three-tiered score [0: normal C-reactive protein (CRP) and albumin; 1: one abnormal result; 2: increased CRP and low albumin]. Higher score means worse outcome. | Visit 1 and Visit 2, approximately 12 weeks | 
| Change in 24 hour urinary AGE levels | Estimated mean levels within the intervention and the control groups of the study. Effect size will be estimated by the 95% confidence intervals within and between groups. | Visit 1 and Visit 2, approximately 12 weeks | 
| Adherence to virtual visit with psychologist or dietician | Number of participants in the intervention and control group that completed virtual visits with the psychologist. | Visit 1 and Visit 2, approximately 12 weeks | 
| Adherence to time period of eating recommendation in both study groups: self reporting during virtual visits and through food photography / annotated entries. | Proportion of days that time period of eating was followed. | Visit 1 and Visit 2, approximately 12 weeks | 
| Time restricted feeding affected sleep patterns | Change in sleep pattern between intervention and control groups as assessed using American Academy of Sleep Medicine 2 week sleep diaries. | Visit 1 and Visit 2, approximately 12 weeks | 
| Peripheral blood mononuclear cell (PMBC) analysis | Peripheral blood mononuclear cells will be analyzed for RAGE expression and compared within and between intervention and control groups. | Visit 1 and Visit 2, approximately 12 weeks | 
| Continuous Glucose Monitor (CGM) derived metrics | Mean glucose, standard deviation (SD) of mean glucose values, co-efficient of variation (CV %) of sensor glucose levels, glucose management indicator (GMI%) from CGM data. Estimated mean levels within the intervention and the control groups of the study. Effect size will be estimated by the 95% confidence intervals within and between groups. | Visit 1 and Visit 2, approximately 12 weeks |