Pharmacological and Behavioral Treatment After Bariatric Surgery: Acute (Stage 1)

Pharmacological and Behavioral Treatments to Treat Loss-of-Control Eating and Improve Weight Outcomes After Bariatric Surgery: Acute (Stage 1)

This study will compare the effectiveness of behavioral and pharmacologic treatments, alone and in combination, for the treatment of loss-of-control eating and weight following bariatric surgery. This is an acute treatment comparing behavioral weight loss alone or in combination with combination naltrexone/bupropion medication.

Study Overview

• Status: Recruiting
• Conditions: Loss-of-control Eating; Obesity/Overweight
• Intervention / Treatment: Other: Placebo; Drug: Naltrexone and Bupropion medication; Behavioral: Behavioral Weight Loss

Detailed Description

Participants who provide informed consent and are determined to be eligible will then participate in the study.

A total of 160 patients with obesity and regular LOC-eating following MBS will be randomly assigned (double-blind) in a balanced factorial (2 X 2) design, to one of four 16-week interventions: BWL+NB, BWL+Placebo, NB, or Placebo. The randomization will be in equal proportions but stratified by surgery type.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Valentina Ivezaj, Ph.D.; Phone Number: 203-785-7210; Email: valentina.ivezaj@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale Department of Psychiatry
      • Contact: Valentina Ivezaj, Ph.D.; Phone Number: 203-785-7210; Email: valentina.ivezaj@yale.edu
      • Principal Investigator: Carlos M Grilo, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be in the age range ≥18 years of age and ≤70 years of age.
• Have a BMI ≥30 (or BMI ≥27 with a medical comorbidity) and ≤50
• Have had laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy
• Approximately six months post-surgery
• Experience regular loss-of-control eating (defined as at least once weekly over the past 28 days)
• Be an otherwise healthy subject without uncontrolled medical problems, as determined by the study physician and medical co-investigators (physical examination, laboratory studies).
• Read, comprehend, and write English at a sufficient level to complete study-related materials.
• Provide a signed and dated written informed consent prior to study participation.

Be available for participation in the study for up to 19 months (7-month treatment plus 12-month follow up).

Exclusion Criteria:

• Has a predisposition to seizures (e.g., subject with a history or evidence of seizure disorder, febrile seizures during childhood, brain tumor, cerebrovascular disease, or significant head trauma; has a family history of idiopathic seizure disorder or is currently being treated with medications or treatment regimens that lower seizure threshold).
• Has a history of anorexia nervosa or history of bulimia nervosa.
• Is currently taking a medication that is a contraindication to NB medication (e.g., MAOI, opiates).
• Is currently using other medications for weight loss.
• Has a history of allergy or sensitivity to bupropion or naltrexone.
• Has a co-existing psychiatric condition that requires hospitalization or more intensive treatment (such as bipolar mood disorders, psychotic illnesses, or severe depression)
• Has untreated hypertension with a seated systolic blood pressure > 160 mmHg, diastolic blood pressure > 100 mmHg, or heart rate > 100 beats/minute.
• Has a history of congenital heart disease, cardiovascular disease, cardiac arrhythmias requiring medication, or a history of cerebrovascular pathology including stroke.
• Has current uncontrolled hypertension.
• Has current uncontrolled Type I or Type II diabetes mellitus.
• Has untreated hypothyroidism with a TSH > 1.5 times the upper limit of normal for the test laboratory with repeat value that also exceeds this limit.
• Has gallbladder disease.
• Has a history of severe renal, hepatic, neurological, chronic pulmonary disease, or any other unstable medical disorder.
• Has a recent history of drug or alcohol dependence (since having bariatric surgery).
• Is currently in active treatment for eating or weight loss.
• Is currently participating in another clinical study in which the subject is or will be exposed to an investigational or a non-investigational drug or device.
• Is breast-feeding or is pregnant or is not using a reliable form of birth control.
• Reports active suicidal or homicidal ideation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants randomly assigned to this arm will receive 16 weeks of placebo. Placebo will be inactive and taken daily in pill form.	Other: Placebo; Placebo will be inactive and taken daily in pill form.
Experimental: Behavioral Weight Loss (BWL) + Naltrexone and Bupropion (NB) medication; Participants randomly assigned to this arm will receive 16 weeks of BWL counseling and NB medication. The naltrexone and bupropion will be taken daily in pill form.	Drug: Naltrexone and Bupropion medication; NB medication will be taken daily in pill form.; Other Names: Contrave; Behavioral: Behavioral Weight Loss; Behavioral Weight Loss (BWL) counseling includes weekly sessions.
Experimental: BWL + Placebo; Participants randomly assigned to this arm will receive 16 weeks of BWL counseling and placebo. Placebo will be inactive and taken daily in pill form.	Other: Placebo; Placebo will be inactive and taken daily in pill form.; Behavioral: Behavioral Weight Loss; Behavioral Weight Loss (BWL) counseling includes weekly sessions.
Experimental: NB medication; Participants randomly assigned to this arm will receive 16 weeks of NB medication taken daily in pill form.	Drug: Naltrexone and Bupropion medication; NB medication will be taken daily in pill form.; Other Names: Contrave

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loss-of-control Eating Frequency	Loss-of-control eating frequency is a continuous variable of loss-of-control eating episodes assessed using the Eating Disorder Examination interview; Loss-of-control eating frequency will be based on the past 28 days and defined as loss-of-control eating episodes per month.	Post-treatment (4 months)
Body Mass Index	BMI is calculated using measured height and weight	Post-treatment (4 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loss-of-control Eating Remission	Categorical: zero episodes/28 days	Post-treatment (4 months)
Weight loss	Categorical: 5% weight loss	Post-treatment (4 months)
Eating Disorder Psychopathology	Eating-disorder psychopathology is a continuous variable as assessed by the global score of the Eating Disorder Examination/Eating Disorder Examination-Questionnaire. Scores range from 0-6 (0=no eating-disorder psychopathology; 6=severe eating-disorder psychopathology).	Post-treatment (4 months)
Depressive Symptoms	Depressive symptoms is a continuous variable of depressive symptomatology as assessed by the self-report measure, the Patient Health Questionnaire - 9. Scores range from 0-27 (0=no depressive symptoms, 27=greater depressive symptoms).	Post-treatment (4 months)

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2021
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Overweight; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Narcotic Antagonists; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Alcohol Deterrents; Dopamine Uptake Inhibitors; Naltrexone; Bupropion
• Other Study ID Numbers: 2000029057; R01DK126637-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No