Naltrexone and Bupropion Combination on Obese,Smoking Patients With Schizophrenia

• ClinicalTrials.gov Identifier: NCT02736474
• Recruitment Status: Completed
• First Posted: April 13, 2016
• Last Update Posted: July 11, 2018
• Sponsor: Shanghai Mental Health Center
• Collaborator: University of Massachusetts, Worcester
• Information provided by (Responsible Party): DU, Jiang, Shanghai Mental Health Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Obese; Cigarette-smoking; Schizophrenia	Drug: Naltrexone; Drug: Placebo Naltrexone; Drug: Bupropion; Drug: Placebo Bupropion	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Naltrexone and Bupropion Combination on Weight Loss and Smoking Cessation in Obese, Cigarette-smoking Patients With Schizophrenia
• Actual Study Start Date: May 2016
• Actual Primary Completion Date: July 2018
• Actual Study Completion Date: July 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Naltrexone and Bupropion; 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; 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.; Drug: Bupropion; 1 capsule（150mg） once per day in the first two weeks，then 2 capsules（300mg） once per day during the rest of the study.
Placebo Comparator: Placebo Naltrexone and Bupropion; 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; Placebo Naltrexone created and masked by the pharmacy to be used as a control.; Drug: Placebo Bupropion; Placebo Bupropion created and masked by the pharmacy to be used as a control.

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in weight at 24 weeks [ Time Frame: Baseline, 24 weeks ]
   evaluate all participants' weight ，weight in kilograms

Secondary Outcome Measures :

1. Numbers of participants who quit smoking [ Time Frame: 24 weeks ]
   evaluate all participants' smoking statues by Exhale carbon monoxide concentrations in part per million。
2. Changes from Baseline Craving for nicotine assessed by Visual Analog Scales (VAS) at 24 weeks [ Time Frame: Baseline, 24 weeks ]
   evaluate all participants' craving for nicotine by Visual Analog Scales (VAS)
3. Depression status assessed by Self-rating depression scale（SDS） [ Time Frame: Baseline，2,4,12，and 24 weeks ]
   evaluate all participants' depression status by Self-rating depression scale（SDS）
4. Anxiety status assessed by Self-Rating Anxiety Scale（SAS） [ Time Frame: Baseline，2,4,12，and 24 weeks ]
   evaluate all participants' depression status by Self-Rating Anxiety Scale（SAS）
5. Clinical symptoms assessed by the Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Baseline，2,4,12，and 24 weeks ]
   evaluate all participants' Clinical symptoms by the Positive and Negative Syndrome Scale (PANSS)
6. Clinical symptoms assessed by clinical global impressions scale（CGI） [ Time Frame: Baseline，2,4,12，and 24 weeks ]
   evaluate all participants' Clinical symptoms by clinical global impressions scale（CGI）
7. Change from baseline in waist circumference at 24 weeks [ Time Frame: Baseline, 24 weeks ]
   evaluate all participants' waist circumference，waist circumference in centimeters
8. Change in Fasting Blood Glucose Levels [ Time Frame: Baseline,12 and 24 weeks ]
9. Change in Fasting Insulin Levels [ Time Frame: Baseline,12 and 24 weeks ]
10. Change in glycosylated hemoglobin [ Time Frame: Baseline,12 and 24 weeks ]
11. Change in Fasting Triglycerides Levels [ Time Frame: Baseline,12 and 24 weeks ]
12. Change in Fasting HDL Cholesterol Levels [ Time Frame: Baseline,12 and 24 weeks ]
13. Change in Homeostasis Model Assessment-Insulin Resistance Levels [ Time Frame: Baseline,12 and 24 weeks ]
14. Change in Fasting LDL Cholesterol [ Time Frame: Baseline,12 and 24 weeks ]
15. Change in leptin [ Time Frame: Baseline,12 and 24 weeks ]
16. Change in ghrelin [ Time Frame: Baseline,12 and 24 weeks ]
17. Resting state functional connectivity of the brain reward circuits on weight loss and smoking cessation [ Time Frame: Baseline,24 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Sponsors and Collaborators

Shanghai Mental Health Center

University of Massachusetts, Worcester

Investigators

• Principal Investigator: Jiang Du, PhD; Chief Physician

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lyu X, Du J, Zhan G, Wu Y, Su H, Zhu Y, Jarskog F, Zhao M, Fan X. Naltrexone and Bupropion Combination Treatment for Smoking Cessation and Weight Loss in Patients With Schizophrenia. Front Pharmacol. 2018 Mar 5;9:181. doi: 10.3389/fphar.2018.00181. eCollection 2018.

• Responsible Party: DU, Jiang, Chief Physician, Shanghai Mental Health Center
• ClinicalTrials.gov Identifier: NCT02736474 History of Changes
• Other Study ID Numbers: MZhao-005
• First Posted: April 13, 2016
• Last Update Posted: July 11, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Bupropion hydrochloride, naltrexone hydrochoride drug combination; Naltrexone; Bupropion; Alcohol Deterrents; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Neurotransmitter Agents; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Anti-Obesity Agents