Naltrexone and Bupropion Combination on Obese,Smoking Patients With Schizophrenia

Study Overview
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Brief Summary
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The purpose of this research is to observe the efficacy of Naltrexone and Bupropion combination on weight loss and smoking cessation from baseline to week 24 compare to placebo.

Detailed Description
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This is a randomized, double-blind, and placebo-controlled study. Subjects with evaluation and confirmation that inclusion and exclusion criteria are met, will be treated with naltrexone sustained release 15mg once per day and bupropion sustained release 150mg once per day in the first two weeks, and naltrexone 25mg once per day and bupropion 300mg once per day during the rest of the study.The purpose of this research is to observe the efficacy of Naltrexone and Bupropion on weight loss and smoking cessation compared to placebo.

Official Title
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Effect of Naltrexone and Bupropion Combination on Weight Loss and Smoking Cessation in Obese, Cigarette-smoking Patients With Schizophrenia

Conditions
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Obese, Cigarette-smoking, Schizophrenia

Intervention / Treatment
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* Drug: Naltrexone
* Drug: Placebo Naltrexone
* Drug: Bupropion
* Drug: Placebo Bupropion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of schizophrenia by the International Classification of Diseases 10th Revision (ICD-10); age between 18 and 65 years old; on stable antipsychotic medication treatment for at least one month; BMI > 28 kg/m2 according to BMI criterion for obesity in the Chinese population ， or BMI>27 kg/m2 in the presence of dyslipidemia, or male with waist circumference over 90cm; smoking at least 10 cigarettes daily for one year or longer; desire to lose weight and quit smoking. Exclusion Criteria: Binge eating or other eating disorders; Current use of weight loss or antidiabetic medications; Current substance use (except nicotine or caffeine); Elevated hepatic transaminase levels (>2.5x normal range); Clinically significant Thyroid Stimulating Hormone（TSH） and/or thyroxine4（T4） abnormalities; History of seizure disorder; History of unstable cardiac problems or other unstable medication conditions; Being pregnant or nursing (for women).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naltrexone and Bupropion<br>Naltrexone 3 tablets（15mg） once per day and Bupropion 1 capsule（150mg） once per day in the first two weeks. Then Naltrexone 5 tablets（25mg） once per day and Bupropion 2 capsules（300mg） once per day during the rest of the study. | Drug: Naltrexone<br>* 3 tablets（15mg） once per day in the first two weeks，then Naltrexone 5 tablets（25mg） once per day during the rest of the study.<br>Drug: Bupropion<br>* 1 capsule（150mg） once per day in the first two weeks，then 2 capsules（300mg） once per day during the rest of the study.<br>|
| Placebo Comparator: Placebo Naltrexone and Bupropion<br>Placebo Naltrexone 3 tablets+Placebo Bupropion 1 capsule once per day in the first two weeks. Then Placebo Naltrexone 5 tablets+Placebo Bupropion 2 capsule once per day during the rest of the study. | Drug: Placebo Naltrexone<br>* Placebo Naltrexone created and masked by the pharmacy to be used as a control.<br>Drug: Placebo Bupropion<br>* Placebo Bupropion created and masked by the pharmacy to be used as a control.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weight at 24 Weeks | evaluate all participants' weight ，weight in kilograms | baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numbers of Participants Who Quit Smoking |  | 24 weeks | 
| Changes From Baseline Craving for Nicotine Assessed by Visual Analog Scales (VAS) at 24 Weeks | The visual analogue scale is a scale that is used to gauge smoking craving. Patients can choose a number from 0 to 10 to show their smoking craving, in which 0 represents no craving and 10 represents intense urge. | baseline and 24 weeks | 
| Depression Status Assessed by Self-rating Depression Scale（SDS） | evaluate all participants' depression status by Self-rating depression scale（SDS)，which has a theoretical value range of 20-80. The SDS total score ranges, with the higher the score representing the higher level of severity of depression. | 24 weeks | 
| Anxiety Status Assessed by Self-Rating Anxiety Scale（SAS） | evaluate all participants' depression status by Self-Rating Anxiety Scale，which has a theoretical value range of 20-80. The SAS total score ranges, with the higher the score representing the higher level of severity of anxiety. | 24 weeks | 
| Clinical Symptoms Assessed by the Positive and Negative Syndrome Scale (PANSS) | Through a simple 40 to 50 minute talk with the patient, the physician scored 30 different symptoms on a scale of 1-7 to get their PANSS score. The total score range from 30-210. The PANSS total score ranges, with the higher the score representing the higher level of severity of clinical symptoms. | 24 weeks | 
| Waist Circumference | evaluate all participants' waist circumference，waist circumference in centimeters | 24 weeks | 
| Change in Fasting Blood Glucose Levels |  | baseline and 24 weeks | 
| Change in Fasting Insulin Levels |  | baseline and 24 weeks | 
| Change in Glycosylated Hemoglobin |  | baseline and 24 weeks | 
| Change in Fasting Triglycerides Levels |  | baseline and 24 weeks | 
| Change in Fasting HDL Cholesterol Levels |  | baseline and 24 weeks | 
| Change in Fasting LDL Cholesterol |  | baseline and 24 weeks | 
| Change in Leptin |  | baseline and 24 weeks | 
| Change in Ghrelin |  | baseline and 24 weeks |