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

Obesity Clinical Trial

— POWERS  

Official title:

Physiology of the Weight Reduced State

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05748158
• Other study ID #: STUDY21120046
• Secondary ID: U24DK128125UH3DK
• Status: Recruiting
• Phase: N/A
• Start date: September 29, 2023
• Est. completion date: December 2026

Study information

• Verified date: March 2024
• Source: University of Pittsburgh
• Contact: Andrew Pelesko, BS
• Phone: 412-383-9584
• Email: ajp67[@]pitt.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 205
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 59 Years

Eligibility

Inclusion Criteria:

1. Age: 25 - <60 years

2. BMI: 30 - <40 kg/m2

3. Within 5% of maximum lifetime weight excluding weights while pregnant and within 1-year post-partum

4. Within 5% of current weight, for the past 6 months

5. Able to participate in ergometry testing

6. Has a smart phone, tablet or computer with access to the internet

Exclusion Criteria:

1. History of pulmonary embolus in the past 6 months

2. Cardiovascular disease (e.g. myocardial infarction, stroke, hospitalization for unstable angina, or transient ischemic attack) within the past 6 months

3. Current major depressive disorder or history of major depressive disorder within 2 years

4. Any regular tobacco or nicotine use in the past year

5. Currently engaging in intense physical training or training for a sports event including, but not limited to, a marathon or body building

6. Currently pregnant, or less than one-year post-partum or actively planning to become pregnant within the next two years

7. Presently classified as being in New York Heart Association Class II or greater or dysrhythmia

8. Diabetes (type 1 or 2 - HbA1c = 6.5%, fasting glucose = 126 mg/dL) or currently taking a glucose lowering medication

9. Thyroid disease requiring hormones or medication or thyroid stimulating hormone (TSH) < 0.5 or > 5 mIU/L

10. Renal disease requiring dialysis

11. Known HIV infection

12. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5 times the upper limit of normal or active gall bladder disease

13. Significant anemia (Hgb < 10 g/dL), leukopenia (WBC < 4,000 /mm3), or thrombocytopenia (platelet count < 60,000 /mm3)

14. 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

15. Current or past history of anorexia nervosa or bulimia nervosa

16. Current or past diagnosis of binge eating disorder

17. Diagnosis of other severe psychiatric disorder (e.g. schizophrenia, bipolar disorder)

18. Unwillingness to abstain from marijuana/cannabis use for 3 weeks at each of the four assessment time points

19. Known or suspected abuse or misuse of alcohol, prescription drugs, or recreational drugs

20. Antiretroviral therapy (ART), including treatment for HIV, pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) within the past 3 months

21. 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)

22. Currently taking anticoagulant medication

23. Currently enrolled in a supervised weight reduction program

24. Prior or planned bariatric surgery, endoscopic therapy, device-based therapy for obesity, liposuction, cryolipolysis, or abdominoplasty

25. 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

26. Current celiac or diagnosed gluten intolerance or inflammatory bowel disease requiring specialized diet

27. Night or rotating shift worker

28. Known severe allergy (e.g. anaphylaxis) to nuts or other foods

29. Systolic blood pressure (BP) <90 mmHg and/or diastolic BP <60 mmHg on 2 measurements during the clinical screening visit.

30. 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.

31. Metal implants, piercings that cannot be removed, or metal-based tattoos or hair treatments

32. Exceeds limitations to fit MRI and dual-energy X-ray absorptiometry (DXA) field of view

33. Known allergy to lidocaine or acetaminophen

34. Non-compliance with appointments or tasks (food diaries, etc.) during the screening phase

35. Blood clotting disorder

36. Tendency to form thick or raised scars

37. Inability to achieve weight stability during the 2 weeks prior to initiation of the baseline Doubly Labeled Water (DLW) assessment

38. At high risk for suicide, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)

Related Conditions & MeSH terms

• Obesity

Intervention

Behavioral:
• Weight loss
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: = 2% weight loss anytime between 28 and 34 days after the start of the intervention = 5% weight loss anytime between 140 and 146 days after the start of the intervention = 7% weight loss by the end of 37 weeks After achieving =7% weight loss followed by weight stability, participants are observed, without further intervention, for 52 weeks.

Locations

Country	Name	City	State
United States	Columbia University Irving Medical Center	New York	New York
United States	Drexel University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (8)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of lost weight that is regained	End of weight stabilization following at least 7 percent weight loss vs. 52 weeks after weight stabilization following at least 7 percent weight loss
Primary	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	Weight regained	End of weight stabilization following at least 7 percent weight loss vs. 52 weeks after weight stabilization following at least 7 percent weight loss

External Links

•   The Physiology of the Weight Reduced State (POWERS) study website