Pharmacological and Behavioral Treatment After Bariatric Surgery

Behavioral and Pharmacological Treatments to Enhance Weight Outcomes After Metabolic and Bariatric Surgery

This study will compare the effectiveness of behavioral and pharmacologic treatment, alone and combined, for improvements in weight loss, cardiovascular risk factors, and psychosocial functioning following metabolic and bariatric surgery.

Study Overview

• Status: Recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Naltrexone and Bupropion Combination; Behavioral: Behavioral Weight Loss; Other: Placebo

Detailed Description

Metabolic and bariatric surgery is currently the most effective treatment for severe obesity; however, a substantial proportion of patients attain suboptimal weight losses and continue to struggle with obesity, weight regain, and related medical comorbidities after surgery. Thus, this study aims to perform a randomized double-blind placebo-controlled study to test the effectiveness of a rigorous manualized behavioral weight loss treatment and a FDA-approved weight loss agent (naltrexone+bupropion), alone and in combination, for improving weight loss, cardiovascular risk factors, and psychosocial functioning after metabolic and bariatric surgery. This study will produce important new clinical findings regarding the utility and effectiveness of pharmacotherapy and behavioral weight loss for a rapidly growing obesity subgroup and will inform care models for managing chronic and refractory obesity to enhance outcomes after metabolic and bariatric surgery.

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

Contacts and Locations

• Study Contact: Name: Carlos M Grilo, Ph.D.; Phone Number: 203-785-7210; Email: carlos.grilo@yale.edu
• Study Contact Backup: 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, 06519
      • Recruiting
      • Yale School of Medicine
      • Contact: Valentina Ivezaj, PhD; Phone Number: 203-785-7807; Email: valentina.ivezaj@yale.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study (up to 18 months: 6-month treatment plus 12-month follow up)
• Have a BMI ≥30 (or BMI ≥27 with a medical comorbidity) and BMI ≤50 kg/m2
• Have had laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy
• Suboptimal weight outcomes after MBS
• Be an otherwise healthy subject without uncontrolled medical problems, as determined by the study physician and medical co-investigators (physical examination, laboratory studies).
• Have had a physical in the past year
• Read, comprehend, and write English at a sufficient level to complete study-related materials.
• For females of reproductive potential: use of highly effective contraception and agreement to use such a method during study participation
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner

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 2 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.
• Is currently in active effective treatment for eating or weight loss such as behavioral weight loss of FDA-approved weight loss medications.
• 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.
• Has poor eye health

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
Experimental: BWL + NB medication; Participants randomly assigned to this arm will receive 6 months of Behavioral Weight Loss (BWL) counseling and NB medication. The naltrexone and bupropion will be taken daily in pill form.	Drug: Naltrexone and Bupropion Combination; Participants in this intervention will take active naltrexone and bupropion pills.; Behavioral: Behavioral Weight Loss; Participants in this intervention will receive behavioral weight loss treatment.
Experimental: BWL + Placebo; Participants randomly assigned to this arm will receive 6 months of Behavioral Weight Loss (BWL) counseling and placebo. Placebo will be inactive and taken daily in pill form.	Behavioral: Behavioral Weight Loss; Participants in this intervention will receive behavioral weight loss treatment.; Other: Placebo; Participants in this intervention will take inactive (placebo) pills.
Experimental: NB medication; Participants randomly assigned to this arm will receive 6 months of NB medication taken daily in pill form.	Drug: Naltrexone and Bupropion Combination; Participants in this intervention will take active naltrexone and bupropion pills.
Placebo Comparator: Placebo; Participants randomly assigned to this arm will receive 6 months of placebo. Placebo will be inactive and taken daily in pill form.	Other: Placebo; Participants in this intervention will take inactive (placebo) pills.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Mass Index (BMI)	BMI is calculated using measured height and weight	Baseline to after the 6-month treatment
Change in Body Mass Index (BMI)	BMI is calculated using measured height and weight	From post-treatment (6-months) to the 12-month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total cholesterol	Total cholesterol will be measured by bloodwork.	From baseline at study enrollment to after the 6-month treatment
Change in Total cholesterol	Total cholesterol will be measured by bloodwork.	From post-treatment (6-months) to the 12-month follow-up
Change in HbA1C	HbA1C will be measured by bloodwork. HbA1C	From baseline at study enrollment to after the 6-month treatment
Change in HbA1C	HbA1C will be measured by bloodwork. HbA1C	From post-treatment (6-months) to the 12-month follow-up
Change in Glucose	Glucose will be measured by bloodwork.	From baseline at study enrollment to after the 6-month treatment
Change in Glucose	Glucose will be measured by bloodwork.	From post-treatment (6-months) to the 12-month follow-up
Change in Loss-of-Control Eating Frequency	Loss-of-control eating frequency is a continuous variable of loss-of-control eating episodes .during the past 28 days assessed using the Eating Disorder Examination interview	From baseline interview at study enrollment to after the 6-month treatment
Change in Loss-of-Control Eating Frequency	Loss-of-control eating frequency is a continuous variable of loss-of-control eating episodes during the past 28 days assessed using the Eating Disorder Examination interview.	From post-treatment (6-months) to the 12-month follow-up
Change in 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 6-month treatment
Change in 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 (6-months) to the 12-month follow-up
Change in Food Craving	Food craving is a continuous variable of food craving as assessed by the Food Craving Inventory. Scores range from 0-5 (0=no food craving; 5=greatest food craving).	From baseline interview at study enrollment to after the 6-month treatment
Change in Food Craving	Food craving is a continuous variable of food craving as assessed by the Food Craving Inventory. Scores range from 0-5 (0=no food craving; 5=greatest food craving).	From post-treatment (6-months) to the 12-month follow-up
Change in Depressive Symptoms	Depressive Symptoms [ Time Frame: From baseline interview at study enrollment to after the 6-month treatment ] Depressive symptoms is a continuous variable of depressive symptomatology as assessed by the self-report measure, the Patient Health Questionnaire - 9. Total scores range from 0-27 (0=no depressive symptoms, 27=greater depressive symptoms). Depressive symptoms is a continuous variable of depressive symptomatology as assessed by the self-report measure, the Patient Health Questionnaire - 9. Total scores range from 0-27 (0=no depressive symptoms, 27=greater depressive symptoms).	From baseline interview at study enrollment to after the 6-month treatment
Change in Depressive Symptoms	Depressive Symptoms [ Time Frame: From baseline interview at study enrollment to after the 6-month treatment ] Depressive symptoms is a continuous variable of depressive symptomatology as assessed by the self-report measure, the Patient Health Questionnaire - 9. Total scores range from 0-27 (0=no depressive symptoms, 27=greater depressive symptoms). Depressive symptoms is a continuous variable of depressive symptomatology as assessed by the self-report measure, the Patient Health Questionnaire - 9. Total scores range from 0-27 (0=no depressive symptoms, 27=greater depressive symptoms).	From post-treatment (6-months) 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 School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2022
• Primary Completion (Estimated): January 12, 2027
• Study Completion (Estimated): January 12, 2028

Study Registration Dates

• First Submitted: November 22, 2021
• First Submitted That Met QC Criteria: December 5, 2021
• First Posted (Actual): December 15, 2021

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 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: 2000029934; 1R01DK125650-01A1 (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