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

NCT ID: NCT03132571

Last Updated: 2019-08-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-01
• Study Completion Date: 2018-07-31

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.

Conditions

Schizophrenia; Diabetes Mellitus, Type 2; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Naltrexone with Bupropion

Oral Naltrexone taken once a day and Oral Bupropion taken once a day for 16 weeks.

Group Type: EXPERIMENTAL

Naltrexone

Intervention Type: DRUG

37.mg oral capsule taken once daily for over the course of the study (16 weeks)

Bupropion

Intervention Type: DRUG

Extended release bupropion taken once daily for the course of the study (16 weeks) flexible dosing up to 450mg target.

Placebo with Bupropion

Oral placebo capsule and Oral Bupropion taken once a day for 16 weeks.

Group Type: PLACEBO_COMPARATOR

Bupropion

Intervention Type: DRUG

Extended release bupropion taken once daily for the course of the study (16 weeks) flexible dosing up to 450mg target.

Placebo

Intervention Type: OTHER

Oral placebo taken once daily for the course of the study (16 week)

Interventions

Naltrexone

37.mg oral capsule taken once daily for over the course of the study (16 weeks)

Intervention Type: DRUG

Bupropion

Extended release bupropion taken once daily for the course of the study (16 weeks) flexible dosing up to 450mg target.

Intervention Type: DRUG

Placebo

Oral placebo taken once daily for the course of the study (16 week)

Intervention Type: OTHER

Other Intervention Names

Revia; Wellbutrin; Zyban

Eligibility Criteria

Inclusion Criteria

1. Age 18 to 75

2. Meet DSM-IV criteria for schizophrenia or schizoaffective disorder based on SCID interview (If bipolar-schizoaffective: need to be adequately stabilized on a mood stabilizer and show no mania history for the past one year, as confirmed by study psychiatrist and patient's clinician)

3. Body Mass Index (BMI) of 28 and over

4. On a stable dose of antipsychotic medication; i.e. at least one month with no dose change, and three months from an antipsychotic switch

5. Deemed to be symptomatically stable by the clinical staff in the last two months

6. Over 7% total body weight increase on antipsychotics for subjects within first year of illness

Exclusion Criteria

1. Meet criteria for current opiate abuse or dependence (confirmed by positive urine drug screen for opiates or, if suspected by study doctor via patient history and or suspicion of occult opiate use.) Note: All subjects will be screened for drugs, not only those suspected of opiate use.

2. A history of seizures in the past five years (confirmed through chart review and discussion with patient's clinician)

3. Meet DSM criteria for Bipolar Disorder

4. History of mania in the past one year (confirmed through chart review and discussion with patient's clinician)

5. Uncontrolled hypertension

6. Insulin dependent diabetes mellitus

7. Current history of dementia, mental retardation

8. Not capable of giving informed consent for participation in the study

9. Women who are pregnant or breast-feeding

10. Physical conditions affecting body weight (e.g. Cushing's disease, polycystic ovary syndrome)

11. Severe liver dysfunction, (serum aminotransferases greater than three times normal), acute infectious hepatitis, liver failure.

12. History of glaucoma.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cenk Tek, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Connecticut Mental Health Center

New Haven, Connecticut, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1606017928

Identifier Type: -

Identifier Source: org_study_id