A Study to Investigate Why Overweight People Regain Weight After a Losing Weight in a Behavioral Weight Loss Program (POWERS)

A Study to Investigate Why Overweight People Regain Weight After a Losing Weight in a Behavioral Weight Loss Program

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Tufts University, Columbia University, New York State Psychiatric Institute, Drexel University, University of Pennsylvania, Dartmouth College

The goal of this clinical trial is to determine the physiological basis for the differences in weight regain among adults (25-59 years old) with obesity following participation in a behavioral weight loss program. Eligible participants will undergo a baseline evaluation after which they will enter an up to 20 week behavioral weight loss program with the goal of losing at least 7 percent of their baseline weight within 37 weeks. Participants who meet the weight loss goal will be asked to remain weight stable for 2 weeks after which they will undergo a clinical examination. They will then be observed for 1 year during which they will undergo 2 additional clinical examinations, one 4 months after completing the weight loss program, and the other 12 months after completing the weight loss program.

Primary Hypothesis: Changes, integrated values and patterns in energy intake (EI), energy expenditure (EE), resting energy expenditure (REE) and non-resting energy expenditure (NREE), contribute to the variability in weight change during the 12 months following weight loss. Assessment time points: Baseline (BL): prior to starting the weight loss intervention T0: at the end of a period of weight stabilization following at least 7 percent weight loss T4: four months (17 weeks) following T0 T12: twelve months (52 weeks) following T0 Secondary Hypotheses: Changes, integrated values and patterns in components of EI and EE (listed below) contribute to variability in weight change during the 12 months following weight loss. EI: Psychosocial, food attitude, and food environment assessments Diet composition Neural activation in food choice/decision-making and cue/taste/reward (functional magnetic resonance imaging [fMRI]) Measures of food choice, delay discounting, and eating in the absence of hunger Gastric emptying, appetite-related peptides, and glucose and lipid excursions in response to a meal EE: Physical activity 24-hour urine catecholamine Muscle contractile efficiency Mitochondrial function in biopsied skeletal muscle Sleep quality and patterns Muscle and adipose tissue gene expression Plasma metabolome, proteome, exosomes and exposome Stool microbiome Specific Aims: Specific Aim 1: Examine total energy expenditure (TEE) and energy intake (EI) at, and between, baseline, the end of the weight stabilization period following at least 7 percent weight loss, 17 weeks and 52 weeks after the end of the weight stabilization period following at least 7 percent weight loss with respect to variability in weight change between the end of the weight stabilization period following at least 7 percent weight loss and 52 weeks after the end of the weight stabilization period following at least 7 percent weight loss. Specific Aim 2: Examine resting energy expenditure (REE) and non-resting energy expenditure (NREE) at, and between, baseline, the end of the weight stabilization period following at least 7 percent weight loss, 17 weeks and 52 weeks after the end of the weight stabilization period following at least 7 percent weight loss with respect to variability in weight change between the end of the weight stabilization period following at least 7 percent weight loss and 52 weeks after the end of the weight stabilization period following at least 7 percent weight loss. Specific Aim 3: Assess endophenotypes of EI (e.g. diet composition, food-choice, decision-making, delay discounting, cue/taste reward, gastric emptying, appetite-related peptides, glucose and lipid excursions in response to a meal, sleep patterns, food and social environments) at and between time points at which they are measured (e.g., baseline, the end of the weight stabilization period following at least 7 percent weight loss, 17 weeks and 52 weeks after the end of the weight stabilization period following at least 7 percent weight loss) and examine their contributions to the variability in weight change between the end of the weight stabilization period following at least 7 percent weight loss and 52 weeks later. Specific Aim 4: Assess endophenotypes of EE (e.g., actigraphy measures, sleep patterns, muscle contractile efficiency, mitochondrial function, muscle and adipose tissue gene expression, plasma metabolome, microbiome, exposome, and environment) at, and between, time points at which they are measured (e.g., baseline, the end of the weight stabilization period following at least 7 percent weight loss, 17 weeks and 52 weeks after the end of the weight stabilization period following at least 7 percent weight loss) and examine their contributions to the variability in weight change between the end of the weight stabilization period following at least 7 percent weight loss and 52 weeks later.

A 37 week behavioral intervention aimed at decreasing energy intake and increasing physical activity.

A behavioral lifestyle program, up to 20 weeks in duration, based on interventions shown to be successful for weight loss such as the Diabetes Prevention Program (DPP), Action for Health in Diabetes (Look AHEAD), and Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy Study (CALERIE). Weekly sessions, led by experienced interventionists, will provide education and behavioral strategies for weight loss focused an energy-reduced diet and physical activity. Participants must meet the following milestones to continue in the study: > 3% weight loss by 4 weeks after the start of the intervention > 5% weight loss by 20 weeks after the start of the intervention > 7% weight loss between weeks 20 and 37 After achieving >7% weight loss and weight stability between weeks 20 and 37, participants are observed, without further intervention, for 52 weeks.

Weight change from end of weight stabilization following at least 7 percent weight loss to 52 weeks after weight stabilization following at least 7 percent weight loss

End of weight stabilization following at least 7 percent weight loss vs. 52 weeks after weight stabilization following at least 7 percent weight loss

Weight change from end of weight stabilization following at least 7 percent weight loss to 52 weeks after weight stabilization following at least 7 percent weight loss

End of weight stabilization following at least 7 percent weight loss vs. 52 weeks after weight stabilization following at least 7 percent weight loss

Inclusion Criteria: Age: 25 - <60 years BMI: 30 - <40 kg/m2 Within 5% of maximum lifetime weight excluding weights while pregnant and within 1-year post-partum Within 5% of current weight, for the past 6 months Able to participate in ergometry testing Has a smart phone, tablet or computer with access to the internet Exclusion Criteria: History of pulmonary embolus in the past 6 months Cardiovascular disease (e.g. myocardial infarction, stroke, hospitalization for unstable angina, or transient ischemic attack) within the past 6 months Current major depressive disorder or history of major depressive disorder within 2 years Any regular tobacco or nicotine use in the past year Currently engaging in intense physical training or training for a sports event including, but not limited to, a marathon or body building Currently pregnant, or less than one-year post-partum or actively planning to become pregnant within the next two years Presently classified as being in New York Heart Association Class II or greater or dysrhythmia Diabetes (type 1 or 2 - HbA1c ≥ 6.5%, fasting glucose ≥ 126 mg/dL) or currently taking a glucose lowering medication Thyroid disease requiring hormones or medication or thyroid stimulating hormone (TSH) < 0.5 or > 5 mIU/L Renal disease requiring dialysis Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5 times the upper limit of normal or active gall bladder disease Significant anemia (Hgb < 10 g/dL), leukopenia (WBC < 4,000 /mm3), or thrombocytopenia (platelet count < 60,000 /mm3) Active cancer or current chemotherapy treatment, or history of cancer requiring treatment in the past 5 years except for non-melanoma skin cancers or cancers that have clearly been cured Current or past history of anorexia nervosa or bulimia nervosa Current or past diagnosis of binge eating disorder Diagnosis of other severe psychiatric disorder (e.g. schizophrenia, bipolar disorder) Unwillingness to abstain from marijuana/cannabis use for 3 weeks at each of the four assessment time points Known or suspected abuse or misuse of alcohol, prescription drugs, or recreational drugs Regularly taking medication or supplement known to affect appetite, energy expenditure, or weight (e.g. appetite suppressants, steroids-including inhaled steroids but not topical, alpha-blockers, beta-blockers, certain psychotropic medications) Currently taking anticoagulant medication Currently enrolled in a supervised weight reduction program Severely restricted diets: Vegan (no meat, fish, dairy, eggs, or honey), very low carbohydrate (<15% calorie as carbohydrate), very low fat (<15% calories as fat), or strictly gluten free Current celiac or diagnosed gluten intolerance or inflammatory bowel disease requiring specialized diet Night or rotating shift worker Known severe allergy (e.g. anaphylaxis) to nuts or other foods Systolic blood pressure (BP) <90 mmHg and/or diastolic BP <60 mmHg on 2 measurements during the clinical screening visit. Systolic blood pressure (BP) >160 mmHg and/or diastolic BP >100 mmHg on at least 2 measurements during the clinical screening visit or resting heart rate < 45 beats per minute or >100 on 2 measurements during the clinical screening visit. Metal implants, piercings that cannot be removed, or metal-based tattoos or hair treatments Exceeds limitations to fit MRI and dual-energy X-ray absorptiometry (DXA) field of view Known allergy to lidocaine Non-compliance with appointments or tasks (food diaries, etc.) during the screening phase Blood clotting disorder Tendency to form thick or raised scars Inability to achieve weight stability during the 2 weeks prior to initiation of the baseline Doubly Labeled Water (DLW) assessment At high risk for suicide, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)

Relevant individual participant data (IPD) will be provided to approved ancillary study investigators. All data will be archived, following the end of the study, at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-supported data repository.

Access to the data for approved ancillary studies will be through the data coordinating center. Access to the data at the NIDDK-repository will be through the NIDDK data repository's process.