Use of Medication to Improve Weight Loss in Suboptimal Early Responders to Behavioral Treatment

NCT03779048 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 832077
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two-phase study. Phase 1 will evaluate obesity-related behavioral and biological characteristics as potential predictors of response to behavioral treatment (BT) for weight loss. Phase 2 is a double-blind, placebo-controlled, RCT to test whether adding weight loss medication to BT improves 24-week weight loss, as compared to BT with placebo, in subjects identified as having suboptimal early weight loss after 4 weeks of individual behavioral weight control. All participants, regardless of their early weight loss, will receive the same BT program of diet, physical activity, and behavior therapy for weight loss for an additional 24 weeks (28 total weeks of treatment).

Conditions

Obesity

Keywords

phentermine; Hypoglycemic agents; Incretins; Hormones; Appetitive Behavior; Appetite Depressants; Anti-Obesity Agents; Weight Loss; Body Weight; Body Weight Changes; Signs and Symptoms

Outcome Measures

Primary Outcomes (6)

• Phase 1: Percent Weight Loss

  Co-primary outcomes - phase 1

  Week -4 (start of BT run-in) to week 0 (randomization)

• Phase 1: Number of Participants Who Are Categorized as Early Non-responders at Randomization (Week 0), Based on Percent Weight Loss

  Co-primary outcomes - phase 1

  Week -4 (start of BT run-in) to week 0 (randomization)

• Phase 1: Baseline Satiety, as Measured by Visual Analogue Scales (Range 0-100 mm) During a Test Meal; Satiety Quotient = [(Post-preload Rating - Fasting Rating Before Preload)] / (Energy Content of Preload in kcal) x 100.

  Primary predictor variable - phase 1 Appetite suppression was first calculated as the average of 100 mm VAS items: hunger (reverse score), satisfaction, fullness, and prospective consumption (reverse score), such that higher scores indicate more appetite suppression (less appetite) for each test meal rating (fasting, then every 10m for 60m). The satiety quotient was then calculated for each post-preload rating using the above formula (see measure title). More positive scores show increased satiety (more appetite suppression). The final analysis uses the 60-minute area under the curve (AUC) for the satiety quotient to predict phase 1 weight loss outcomes. Area under the curve is calculated using the trapezoidal rule to sum the area under each 10-minute interval. AUC = Σ i = 0 to i = 60 10min\*(x(i) + x(i-1))/2) where x is the satiety quotient value at time i. Higher scores indicate higher sustained satiety.

  Baseline (week -5)

• Phase 1: Baseline Postprandial Change in GLP-1 During a Test Meal

  Primary predictor variable - phase 1. Blood samples were drawn at time 0 (fasting) and 30- and 60-min postprandial samples after consumption of a test meal. Value presented below is the 60-minute incremental area under the curve (AUC) for GLP-1 in picomoles (pM). Area under the curve is calculated using the trapezoidal rule to sum the area under each 0.5-hour interval. AUC = Σ i = 0 to i = 1 0.5hr\*(x(i) + x(i-1))/2) where x is the GLP-1 value in pM at time i.

  Baseline

• Phase 1: Baseline Gastric Emptying During a Test Meal (Acetaminophen Test)

  Primary predictor variable - phase 1 Gastric emptying was measured as the 60-minute area under the curve (AUC) for acetaminophen in micrograms per milliliter (ug/mL). Blood samples were obtained at time 0 (fasting/no acetaminophen - confirmatory) and 30 and 60-min after ingestion. Because acetaminophen is minimally absorbed by the stomach but quickly enters the bloodstream in the small intestine, gastric emptying is considered to be the primary factor influencing its appearance in the blood. Area under the curve is calculated using the trapezoidal rule to sum the area under each 0.5-hour interval. AUC = Σ i = 0 to i = 1 0.5hr\*(x(i) + x(i-1))/2) where x is the acetaminophen value in ug/mL at time i.

  Baseline

• Phase 2: Percent Weight Loss

  Primary outcomes - phase 2 Percent change from randomization in body weight

  Week 0 (randomization) to week 24

Secondary Outcomes (14)

• Phase 1: Baseline Hunger, as Measured by Visual Analogue Scales (Range 0-100 mm, Higher = More Hunger) During a Test Meal

  Baseline

• Phase 1: Baseline Relative Reinforcing Value of Food (Computer Task), Number of Food Reinforcer Points Earned

  Baseline

• Phase 1: Baseline Delay Discounting (Computer Task), Area Under the Curve Representing the Ratio of Immediate Reward Size to Time Delay

  Baseline

• Phase 1: Baseline Implicit Wanting, Reaction Time on Leeds Food Preference Questionnaire

  Baseline

• Phase 1: Baseline Fasting Ghrelin

  Baseline

Other Outcomes (27)

• Phase 1: Baseline Eating Behavior as Measured by The Eating Inventory (EI); Dietary Restraint Subscale (Scored 0-21 Higher=More Restraint), Disinhibition Sub Scale (Scored 0-16 Higher=More Disinhibition), Hunger Sub Scale (Scored 0-14 Higher=More Hunger)

  Baseline

• Phase 1: Baseline Appetite Ratings (Ratings of Appetite During the Past Week Using Visual Analogue Scales, Scored 0-100 mm, Higher=Greater Amount or Frequency)

  Baseline

• Phase 1: Baseline Reinforcing Value of Food as Measured by the Power of Food Scale

  Baseline

Study Arms (3)

Phase 2: Behavioral Treatment + Placebo

ACTIVE COMPARATOR

Participants with suboptimal early weight loss in the BT run-in will then be randomly assigned to 24 additional weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M; phentermine 15.0 mg) in a double-blinded fashion. Both treatment groups will continue to attend individual BT sessions and will take a once daily study medication (placebo or phentermine 15.0 mg) for the duration of the intervention period. Early BT responders identified during the run-in will receive the same 24-week BT program, but will not receive study medication or be included in the randomized trial.

Behavioral: Behavioral Treatment; Drug: Placebo

Phase 2: Behavioral Treatment + Medication

ACTIVE COMPARATOR

Participants with suboptimal early weight loss in the BT run-in will then be randomly assigned to 24 additional weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M; phentermine 15.0 mg) in a double-blinded fashion. Both treatment groups will continue to attend individual BT sessions and will take a once daily study medication (placebo or phentermine 15.0 mg) for the duration of the intervention period. Early BT responders identified during the run-in will receive the same 24-week BT program, but will not receive study medication or be included in the randomized trial.

Behavioral: Behavioral Treatment; Drug: Phentermine 15 MG

Phase 1: 4-week Behavioral Treatment Run-in

OTHER

All enrolled participants will complete an initial 4-week behavioral treatment (BT) run-in. This run-in will be used to identify early non-responders to BT, defined by a weight loss \<2% of initial weight after 4 weeks of BT. Early responders are those who lose \>=2%. Only early non-responders will then be enrolled in the randomized trial.

Behavioral: Behavioral Treatment

Interventions

Behavioral Treatment BEHAVIORAL

Behavioral treatment (BT) for weight loss includes diet and physical activity recommendations and behavior therapy strategies. All participants will complete an initial 4-week BT run-in, delivered in individual, 20-30 minute weekly sessions. After the end of the run-in, participants will be offered an additional 24 weeks of 20-30 minute individual BT sessions, occurring weekly for the first 12 weeks and every other week for the last 12 weeks (total of 18 visits).

Also known as: Lifestyle modification, Behavioral weight loss

Phase 1: 4-week Behavioral Treatment Run-in; Phase 2: Behavioral Treatment + Medication; Phase 2: Behavioral Treatment + Placebo

Placebo DRUG

The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.

Also known as: Placebo for medication

Phase 2: Behavioral Treatment + Placebo

Phentermine 15 MG DRUG

The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.

Also known as: Medication

Phase 2: Behavioral Treatment + Medication

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI ≥ 31 kg/m² (or 28 kg/m2 with obesity-related comorbidity)
• Age ≥ 21 years and ≤ 70 years
• Eligible female patients will be:
• non-pregnant, evidenced by a negative urine pregnancy test
• non-lactating
• surgically sterile or postmenopausal, or they will agree to continue to use an accepted method of birth control during the study. Acceptable methods of birth control are: hormonal contraceptives; double barrier method (condom with spermicide or diaphragm with spermicide); intrauterine device; surgical sterility; abstinence; and/or postmenopausal status (defined as at least 2 years without menses).
• Subjects must:
• have a primary care provider (PCP) who is responsible for providing routine care
• understand and be willing to comply with all study-related procedures and agree to participate in the study by giving written informed consent
• plan to remain in the Philadelphia area for the next 9 months or more

You may not qualify if:

• Pregnant or nursing, or plans to become pregnant in the next 9 months.
• Uncontrolled hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg)
• Type 1 diabetes
• Type 2 diabetes
• A fasting blood glucose \> 126 mg/dL (on second assessment after first elevated value)
• History of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias, congestive heart failure, or heart block greater than first degree
• Clinically significant hepatic or renal disease
• Hyperthyroidism
• Other thyroid disease, not controlled
• History of malignancy (except for non-melanoma skin cancer) in past 5 years
• Narrow angle glaucoma
• Presence or history of marked agitation
• Current severe major depressive episode (BDI-II score ≥ 29), current active suicidal ideation, or history of suicide attempts within the past 5 years.
• Any severity of thought or bipolar disorder, or bulimia nervosa.
• Psychiatric hospitalization within the past 6 months

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Pennsylvania Center for Weight and Eating Disorders

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Tronieri JS, Ghanbari E, Chevinsky J, LaFata EM, Minnick AM, Rajpal S, Wang SY, Burcaw K, Berkowitz RI, Wadden TA. Anti-obesity medication for weight loss in early nonresponders to behavioral treatment: a randomized controlled trial. Nat Med. 2025 May;31(5):1653-1660. doi: 10.1038/s41591-025-03556-3. Epub 2025 Mar 7.

  PMID: 40055520 DERIVED

MeSH Terms

Conditions

Obesity; Appetitive Behavior; Anorexia; Weight Loss; Body Weight; Body Weight Changes; Signs and Symptoms

Interventions

Behavior Therapy; Dosage Forms; Phentermine

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Pathological Conditions, Signs and Symptoms; Behavior, Animal; Behavior; Signs and Symptoms, Digestive

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities; Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Dr. Jena Tronieri
• Organization: University of Pennsylvania

jena.tronieri@pennmedicine.upenn.edu

2157465045

Study Officials

• Jena S Tronieri, PhD

  Perelman School of Medicine at the University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1 is observational. Phase 2 is a double-blind, placebo-controlled, randomized controlled trial.

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 19, 2018
• Study Start: July 15, 2019
• Primary Completion: May 25, 2022
• Study Completion: May 25, 2022
• Last Updated: March 11, 2025
• Results First Posted: March 11, 2025

Record last verified: 2025-02

Locations

US (1)