Obesity
Conditions
Keywords
Key words provided by Michael Wilkinson, MD, University of California San Diego:, Catecholamine Sensitivity, Circadian Rhythm, Fasting, Obesity, Time Restricted Eating, Weight Loss
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.
Interventions
BEHAVIORALStandard of Care
Participants in this arm will receive nutritional counseling from the study dietician but will not be required to adopt a 10-hr eating window.
BEHAVIORALTime Restricted Eating
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.
Sponsors
University of California, San Diego
Salk Institute for Biological Studies
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of TRE on Body Weight | Baseline to end of 12 week intervention | Measured as change in weight (kg). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effects of TRE on Body Composition | Baseline to end of 12 week intervention | Measured as change in percent body fat. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMichael J Wilkinson, MD
University of California, San Diego
Participant flow
Recruitment details
Participants were recruited based on physician referral at a single academic center between November 2020 and February 2023. The first potential participant screened for study eligibility was on December 3, 2020 (enrolled (randomized) December 17, 2020) and the last participant screened for eligibility was in February 2023.
Pre-assignment details
Out of 85 potential participants screened for study eligibility, 61 met the inclusion criteria and were subsequently randomized to treatment. One participant was excluded from analysis because of an underlying muscular dystrophy known to affect body composition.
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care (SOC) 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.
Standard of Care: Participants in this arm will receive nutritional counseling from the study dietician but will not be required to adopt a 10-hr eating window. | 31 |
| TRE + SOC 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
Time Restricted Eating: 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. | 29 |
| Total | 60 |
Baseline characteristics
| Characteristic | Standard of Care (SOC) | TRE + SOC | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 7 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 22 Participants | 46 Participants |
| Body Mass Index (BMI) | 34.7 Kg^m2 STANDARD_DEVIATION 3.5 | 36.3 Kg^m2 STANDARD_DEVIATION 5.9 | 35.5 Kg^m2 STANDARD_DEVIATION 4.8 |
| Body Weight | 100.9 Kg STANDARD_DEVIATION 14.7 | 101.9 Kg STANDARD_DEVIATION 20.8 | 101.4 Kg STANDARD_DEVIATION 17.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 5 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 23 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 18 Participants | 20 Participants | 38 Participants |
| Region of Enrollment United States | 31 Participants | 29 Participants | 60 Participants |
| Sex: Female, Male Female | 16 Participants | 19 Participants | 35 Participants |
| Sex: Female, Male Male | 15 Participants | 10 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 30 |
| other Total, other adverse events | 0 / 31 | 0 / 30 |
| serious Total, serious adverse events | 0 / 31 | 0 / 30 |
Outcome results
Primary
Effects of TRE on Body Weight
Measured as change in weight (kg).
Time frame: Baseline to end of 12 week intervention
Population: Intent to treat population (all participants assigned to Standard of Care (SOC) or TRE + SOC).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Standard of Care (SOC) | Effects of TRE on Body Weight | -1.68 Kg |
| TRE + SOC | Effects of TRE on Body Weight | -4.59 Kg |
p-value: <0.001t-test, 2 sided
Secondary
Effects of TRE on Body Composition
Measured as change in percent body fat.
Time frame: Baseline to end of 12 week intervention
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Standard of Care (SOC) | Effects of TRE on Body Composition | -0.8 percentage of body fat |
| TRE + SOC | Effects of TRE on Body Composition | -1.3 percentage of body fat |
Other Pre-specified
Effects of TRE on Catecholamine Sensitivity of Obese Adipose Tissue (Exploratory Outcome)
Measured as release of free fatty acids (uM).
Time frame: Baseline to end of 12 week intervention
Population: These experiments were not technically feasible with human adipose tissue
Other Pre-specified
Effects of TRE on Inflammation in Obese Adipose Tissue (Exploratory Outcome)
Measured as inflammatory marker mRNA.
Time frame: Baseline to end of 12 weeks
Population: These experiments could not be conducted as planned because of budgetary constraints.