Pharmacological and Behavioral Treatments After Bariatric Surgery: Maintenance Treatment (Stage 2a)

Pharmacological and Behavioral Treatments to Treat Loss-of-Control Eating and Improve Weight Outcomes After Bariatric Surgery: Maintenance Treatment (Stage 2a)

This study will test the effectiveness of naltrexone/bupropion medication as a maintenance therapy for the treatment of loss-of-control eating and weight loss following bariatric surgery. This is a controlled test of whether, amongst responders to acute treatments, naltrexone/bupropion medication results in superior maintenance and longer-term outcomes compared with placebo.

Study Overview

• Status: Enrolling by invitation
• Conditions: Obesity/Overweight; Loss-of-Control Eating
• Intervention / Treatment: Other: Placebo; Drug: Naltrexone and Bupropion (NB) medication

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine

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 had laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy
• Approximately ten months post-surgery
• Experienced regular loss of control eating about six months after bariatric surgery, and were considered treatment responders to a four-month treatment trial of medication and/or BWL
• 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 15 months (3-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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo will be inactive and taken daily in pill form.
Experimental: Naltrexone+Bupropion Medication	Drug: Naltrexone and Bupropion (NB) 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
Body Mass Index (BMI)	BMI is calculated using measured height and weight	From baseline at study enrollment to after the 12-week treatment
Body Mass Index (BMI)	BMI is calculated using measured height and weight	From post-treatment to the 6-month follow-up
Body Mass Index (BMI)	BMI is calculated using measured height and weight	From post-treatment to the 12-month follow-up
Loss-of-control eating Relapse	Relapse will be scored as a yes/no (categorical variable); this categorical variable will be based on frequency of loss-of-control eating episodes assessed using the Eating Disorder Examination interview; Relapse category will be defined as ≥4 loss-of-control eating per month.	From baseline interview at study enrollment to after the 12-week treatment
Loss-of-control eating Relapse	Relapse will be scored as a yes/no (categorical variable); this categorical variable will be based on frequency of loss-of-control eating episodes assessed using the Eating Disorder Examination interview; Relapse category will be defined as ≥4 loss-of-control eating per month.	From post-treatment to the 6-month follow-up
Loss-of-control eating Relapse	Relapse will be scored as a yes/no (categorical variable); this categorical variable will be based on frequency of loss-of-control eating episodes assessed using the Eating Disorder Examination interview; Relapse category will be defined as ≥4 loss-of-control eating per month.	From post-treatment to the 12-month follow-up

Secondary 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.	From baseline interview at study enrollment to after the 12-week treatment
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.	From post-treatment to the 6-month follow-up
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.	From post-treatment to the 12-month follow-up
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).	From baseline interview at study enrollment to after the 12-week treatment
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).	From post-treatment to the 6-month follow-up
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).	From post-treatment to the 12-month follow-up
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).	From baseline at study enrollment to after the 12-week treatment
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).	From post-treatment to the 6-month follow-up
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).	From post-treatment to the 12-month follow-up

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Valentina Ivezaj, Ph.D., Yale University

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2022
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 27, 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: 2000029057a; 5R01DK126637-02 (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