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

Sponsor

University of Pittsburgh (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05748158

Collaborator

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

205

Enrollment

Locations

Arm

Anticipated Duration (Months)

51.3

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Behavioral: Weight loss	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

205 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Physiology of the Weight Reduced State

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2026

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Other: Weight loss A 37 week behavioral intervention aimed at decreasing energy intake and increasing physical activity.	Behavioral: Weight loss A behavioral lifestyle program, lup 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.

Arm

Intervention/Treatment

Other: Weight loss

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

Behavioral: Weight loss

A behavioral lifestyle program, lup 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.

Outcome Measures

Primary Outcome Measures

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]
Percentage of lost weight that is regained
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 regained

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 59 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 medications known to affect appetite 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University Irving Medical Center	New York	New York	United States	10032
2	New York State Psychiatric Institute	New York	New York	United States	10032
3	Drexel University	Philadelphia	Pennsylvania	United States	19104
4	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104