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

Not Applicable

Active, not recruiting

• Conditions: Obesity
• Interventions: Behavioral: Standard of Care; Behavioral: Time Restricted Eating

• Registration Number: NCT04916730
• Lead Sponsor: University of California, San Diego

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.

Study Timeline

• Study Start: 2019-11-16
• Study First Submitted: 2021-04-30
• Study First Submitted QC: 2021-06-03
• Study First Posted: 2021-06-07
• Primary Completion: 2023-05-26
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-22
• Last Update Posted: 2024-01-24
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 61

Inclusion Criteria

1. Age: ≥ 18 years old
2. BMI 30-50 kg/m2
3. Own a smartphone with Apple iOS or Android OS
4. Baseline eating window ≥ 14 hours/day
5. 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

1. Taking insulin or anti-diabetic medications within the last 6 months.
2. Manifest diabetes, defined as fasting glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%, or diagnosis of diabetes.
3. Currently taking any medication that is meant for, or has known effect on, appetite or body weight
4. Pregnant or breast-feeding women.
5. Caregiver for a dependent requiring frequent nocturnal care/sleep interruptions. Shift workers with variable (e.g. nocturnal) hours.
6. Planned international travel (time zone changes) during study period.
7. Taking therapeutic anticoagulation which might increase risk of bleeding from adipose tissue biopsy
8. History of surgical intervention for weight loss.
9. History of eating disorder
10. Currently enrolled in a weight-loss or weight-management program
11. On a special or prescribed diet for other reasons (e.g. Celiac disease)
12. Known inflammatory and/or rheumatologic disease
13. Active tobacco abuse or illicit drug use or history of treatment for alcohol abuse
14. History of bone marrow or solid organ transplant
15. History of heart failure
16. History of major adverse cardiovascular events (acute coronary syndrome (ACS), percutaneous coronary intervention, coronary artery bypass graft surgery, stroke/transient ischemic attack (TIA)).
17. History of atrial fibrillation or atrial flutter
18. 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.
19. 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)
20. History of adrenal disease
21. History of cirrhosis
22. History of stage 4 or 5 chronic kidney disease or requiring dialysis
23. History of HIV/AIDS
24. Uncontrolled psychiatric disorder (including history of hospitalization for psychiatric illness).
25. History of obstructive sleep apnea (not on stable positive pressure therapy or other treatment for at least 3 months prior to enrollment)
26. 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care (SOC)	Standard of Care	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.
TRE + SOC	Time Restricted Eating	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

Primary Outcome Measures

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

Trial Locations

Locations (1)

Altman Clinical and Translational Research Institute; 🇺🇸 La Jolla, California, United States