Effect of Time-restricted Eating on Catecholamine-sensitivity of Adipose Tissue in Obese Adults

Study Overview
=================
Brief Summary
-----------------
In a randomized controlled trial, the investigators intend to measure the health impact of time-restricted eating (TRE) in obese patients (body mass index (BMI) ≥ 30 kg/m2), who habitually eat for more than 14 hours every day. Patients will be randomly assigned to a control group of behavioral nutritional counseling (standard of care) or the intervention group of behavioral nutrition counseling with the addition of adopting a 10-hour eating window for 12 weeks (TRE).

Detailed Description
-----------------
The current worldwide epidemic of obesity puts millions of people at increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), and while insulin resistance has been a traditional focus of treatment, resistance to catecholamines in obesity is likely a key factor hampering weight loss efforts. Catecholamines are key drivers of lipolysis in adipose tissue and bind to beta-3 adrenergic receptors (ADRB3) on the surface of adipocytes. Chronic inflammation is characteristic of obesity and suppresses the expression of adipocyte ADRB3, increasing fat storage. This leaves adipose tissue metabolically inflexible and in a state of energy preservation instead of burning fat to promote and maintain weight loss. Thus, catecholamine resistance of adipose tissue is an important target for lifestyle and therapeutic intervention. Time-restricted eating (TRE) is a therapeutic intervention that promotes weight loss and healthier metabolism by aligning dietary intake with circadian rhythms. In this RCT, individuals with obesity will be enrolled in a 14-week study of TRE and behavioral nutritional counseling vs behavioral nutritional counseling alone. In the TRE group, dietary intake will be limited to a self-selected 10-hour window. Information will be collected about adipose tissue catabolism (lipolysis) using samples collected by adipose tissue biopsy of subcutaneous abdominal adipose tissue.

Official Title
-----------------
Effect of Time-restricted Eating on Catecholamine-sensitivity of Adipose Tissue in Obese Adults

Conditions
-----------------
Obesity

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: ≥ 18 years old BMI 30-50 kg/m2 Own a smartphone with Apple iOS or Android OS Baseline eating window ≥ 14 hours/day If patients are on cardiovascular medications (HMG CoA reductase inhibitors (statins), other lipid modifying drugs (including over the counter drugs such as red yeast rice and fish oil), anti-hypertensive drugs, no dose adjustments will be allowed during the study period. Exclusion Criteria: Taking insulin or anti-diabetic medications within the last 6 months. Manifest diabetes, defined as fasting glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%, or diagnosis of diabetes. Currently taking any medication that is meant for, or has known effect on, appetite or body weight Pregnant or breast-feeding women. Caregiver for a dependent requiring frequent nocturnal care/sleep interruptions. Shift workers with variable (e.g. nocturnal) hours. Planned international travel (time zone changes) during study period. Taking therapeutic anticoagulation which might increase risk of bleeding from adipose tissue biopsy History of surgical intervention for weight loss. History of eating disorder Currently enrolled in a weight-loss or weight-management program On a special or prescribed diet for other reasons (e.g. Celiac disease) Known inflammatory and/or rheumatologic disease Active tobacco abuse or illicit drug use or history of treatment for alcohol abuse History of bone marrow or solid organ transplant History of heart failure History of major adverse cardiovascular events (acute coronary syndrome (ACS), percutaneous coronary intervention, coronary artery bypass graft surgery, stroke/transient ischemic attack (TIA)). History of atrial fibrillation or atrial flutter History of malignancy, other than non-melanoma skin cancer, that is currently being treated, or that has not been treated with definitive therapy and considered to be in remission. History of hypo- or hyperthyroidism 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 cirrhosis 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). History of obstructive sleep apnea (not on stable positive pressure therapy or other treatment for at least 3 months prior to enrollment) Abnormal screening labs: renal dysfunction (eGFR < 30 ml/min/1.73 m2), anemia, hypo- or hyperthyroidism, coagulopathy, abnormal liver function (AST, ALT > 3x upper limit of normal)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

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

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

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 (SOC)<br>Participants will receive standard of care nutritional behavioral counseling and will be required to log their caloric intake through the use of a smartphone app. | Behavioral: Standard of Care<br>* Participants in this arm will receive nutritional counseling from the study dietician but will not be required to adopt a 10-hr eating window.<br>|
| Experimental: TRE + SOC<br>Participants in this arm will receive standard of care nutritional behavioral counseling and will implement a daily, self-selected, 10-hour window within which they must consume all calories. They will also be required to log their caloric intake through the use of a smartphone app | Behavioral: Time Restricted Eating<br>* Participants in this arm will adhere to a daily, consistent self-selected 10-hr eating window for the course of the study intervention period as well as receive nutritional counseling from the study dietitian.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of TRE on body weight | Measured as weight (kg). | Baseline to 14 weeks | 
| Effects of TRE on body composition | Measured as percent body fat. | Baseline to 14 weeks | 
| Effects of TRE on catecholamine sensitivity of obese adipose tissue (Exploratory Outcome) | Measured as release of free fatty acids (uM). | Baseline to 14 weeks | 
| Effects of TRE on inflammation in obese adipose tissue (Exploratory Outcome) | Measured as inflammatory marker mRNA. | Baseline to 14 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Key words provided by Michael Wilkinson, MD, University of California San Diego:, Catecholamine Sensitivity, Circadian Rhythm, Fasting, Obesity, Time Restricted Eating, Weight Loss