Naltrexone-Bupropion Versus Placebo-Bupropion for Weight Loss in Schizophrenia

Phase 2

Terminated

Conditions: Obesity
Diabetes Mellitus, Type 2
Schizophrenia

Interventions: Drug: Naltrexone
Drug: Bupropion
Other: Placebo

Registration Number: NCT03132571

Lead Sponsor: Yale University

Brief Summary: The purpose of this study is to determine the efficacy of combining open-label extended release bupropion (flexible dosing up to 450mg target) and naltrexone (37.5mg) versus Bupropion and placebo along with a daily 500 calorie reduction diet recommendation for weight and health risk reduction in 40 overweight/obese individuals with schizophrenia.

Detailed Description: The combination of naltrexone with noradrenaline/dopamine reuptake blocker bupropion has been developed and FDA-approved for the treatment of obesity in the general population. Naltrexone does not normally produce weight loss in humans and bupropion produces modest weight loss, however the combination produces clinically significant weight loss, which appears to be more than the sum of its components would otherwise produce separately. Of interest to us, the combination has been shown to be effective for clinically significant weight loss in obese subjects with type 2 diabetes as well. Registration studies by the manufacturer of the combination pill excluded antipsychotic medication users, thus we have no information on the potential effectiveness of the combination in this population. Both naltrexone and bupropion are commonly used in psychiatry, naltrexone for co-morbid alcohol addiction, and bupropion for co-morbid depression and/or cigarette addiction. This is a 16-week pilot trial of 37.5mg naltrexone/placebo added to extended release bupropion in flexible dosing (150mg to 450mg) and a daily 500 calorie reduction diet recommendation for subjects with schizophrenia and obesity. A dose of 37.5mg is similar to the FDA-approved combination dose for naltrexone. However, based on our experience with bupropion, we have chosen to use bupropion in an un-blinded manner and reach the target dose of 450mg based on tolerance of the individual subject over the initial 3-week period.

Changes to the study since registration:

The study was initially registered with 3 arms (Naltrexone vs Bupropion vs Placebo)- whereas the original intent was always supposed to be a 2 armed study (Naltrexone vs Placebo- each with Bupropion included)- this was corrected when the results of the terminated study were entered. In addition, there was an initial intent to include diabetics in the study, but this was later removed as well.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 5

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo with Bupropion	Placebo	Oral placebo capsule and Oral Bupropion taken once a day for 16 weeks.
Naltrexone with Bupropion	Naltrexone	Oral Naltrexone taken once a day and Oral Bupropion taken once a day for 16 weeks.
Placebo with Bupropion	Bupropion	Oral placebo capsule and Oral Bupropion taken once a day for 16 weeks.
Naltrexone with Bupropion	Bupropion	Oral Naltrexone taken once a day and Oral Bupropion taken once a day for 16 weeks.

Primary Outcome Measures

Name	Time	Method
BMI	Baseline and Week 16	BMI will be calculated using weekly height and weight measurements (kg/m\^2) at each assessment.

Secondary Outcome Measures

Name	Time	Method
Waist Circumference (Inches)	Baseline and Week 16	Waist circumference will be measured in inches at each assessment.
Weight (kg)	Baseline and Week 16	Weight in kilograms will be measured at each assessment and change will be determined at study endpoint.
Health Risk Markers	Baseline to Week 16	Serum lipid profiles, fasting glucose, and glycosylated hemoglobin (hbA1c) will be measured at baseline and week 16 and change in these markers will be determined at endpoint