Clinical trial NCT02736474
Conditions: Obese Cigarette-smoking Schizophrenia
Sponsor: Shanghai Mental Health Center
Start date: 2016-05-01; Completion date: 2018-07-01
Enrollment: 22 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

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.

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: Naltrexone intervention 2: Placebo Naltrexone intervention 3: Bupropion intervention 4: Placebo Bupropion
Intervention descriptions: intervention 1: 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. intervention 2: Placebo Naltrexone created and masked by the pharmacy to be used as a control. intervention 3: 1 capsule（150mg） once per day in the first two weeks，then 2 capsules（300mg） once per day during the rest of the study. intervention 4: Placebo Bupropion created and masked by the pharmacy to be used as a control.

Protocol documents:
Prot_000.pdf: 
Naltrexone and Bupropion Combination on Obese, Smoking 
Patients With Schizophrenia 
NCT02736474 
2015.12.30. 
 
 


Subjects:  A total number of 60 subjects will be recruited for the 
study with 30 of them to complete the imaging assessment.  The 
major inclusion criteria are: 1) diagnosis of schizophrenia; 2) age 
between 18 and 65 years; 3) on stable antipsychotic medication 
regimen for at least one month; 4) BMI > 28 kg/m2 using the BMI 
criterion for obesity in the Chinese population; 5) smoking at least 
10 cigarettes daily for a minimum of 1 year; 6) desire to lose weight 
and quit smoking.  The exclusion criteria are: 1) binge eating or 
other eating disorders; 2) current use of weight loss medications; 3) 
current substance use (except nicotine or caffeine); 4) elevated 
hepatic transaminase levels (>2.5x normal range); 5) clinically 
significant TSH and/or T4 abnormalities; 6) history of seizure 
disorder; 7) history of unstable cardiac problems or other unstable 
medication conditions; 8) being pregnant or nursing (for women).  
 
Screening visit:  After written informed consent is obtained, a 
diagnosis of schizophrenia will be determined by the International 
Classification of Diseases 10th Revision (ICD-10) by a research 
psychiatrist.  A medical history and physical examination will be 
obtained by a research psychiatrist to assess inclusionary and 
exclusionary criteria, including current medications, substance use 
and number of cigarettes smoked daily. A urine pregnancy test will 


be performed for women of childbearing potential. In addition, a 
urine drug screen, and a 12-lead EKG will be performed.  
 
Baseline visit:  Eligible subjects will come to the clinic for the 
baseline assessment including: 1) height, weight and waist 
circumference; 2) Fasting blood samples for glucose, insulin, leptin, 
ghrelin, HbA1c, lipid profile, comprehensive metabolic profile, CBC, 
high sensitivity CRP, IL-6 and TNF-α; 3) breath CO level; 4) smoking 
craving using the Visual Analogue Scale; 5) number of cigarettes 
smoked in the past week; 6) the Positive and Negative Syndrome 
Scale (PANSS), 7) the side effects questionnaire. On a separate 
day, subjects who participate in the imaging assessment will 
complete the brain MRI scans.  Subjects will then receive the study 
drug (either combination medication or placebo). The randomization 
is based on a 1:1 ratio using permuted block randomization, 
stratified by imaging assessment participation.  In addition, 
subjects will receive the first session lifestyle counseling. 
 
Follow-up visits: Subjects will be followed at weeks 2, 4, then every 
4 weeks to receive the study drug and the lifestyle counseling. 
Weight, breath CO, and possible side effects will be assessed 
during each visit. Waist circumference, scales, the clinical 


symptoms assessment will be repeated every 4 weeks. Fasting 
blood samples for glucose, insulin, leptin, ghrelin, HbA1c, lipid 
profile, comprehensive metabolic profile, CBC, high sensitivity CRP, 
IL-6 and TNF-α will be repeated at weeks 12, 24. Those subjects 
who participate in the imaging assessment, will repeat the brain MRI 
scans at week 24. 
 
Intervention: This is a randomized, double-blind, placebo-controlled 
study. Following screening and confirmation that inclusion and 
exclusion criteria are met, subjects will be treated with naltrexone 
sustained release 15mg once per day and bupropion sustained 
release 150mg once per day in the first two weeks. Then subjects 
take naltrexone 15mg twice per day and bupropion 150mg twice per 
day during the rest of the study.  The dosing choice of NB is based 
on the efficacy and side effects of various dosing strategies reported 
in previous NB trials as well as the supply availability of both 
naltrexone and bupropion in China. Subjects will be maintained on 
the same antipsychotic at the same dose whenever possible during 
the study; however the subject’s clinical well-being will determine 
antipsychotic dosing. Subjects will return to meet with an 
investigator every 2 weeks for the first 4 weeks, then every 4 weeks 
to review medical and psychiatric status.  Compliance will be 


assessed by pill counts at each meeting. Subjects also receive 
culturally sensitive lifestyle counseling during each visit. 
 

SAP_001.pdf: 
Naltrexone and Bupropion Combination on Obese, Smoking 
Patients With Schizophrenia 
NCT02736474 
2015.12.30. 
 
 


The sample of 60 evaluable subjects will have 80% power to detect 
a 4.5 kg differential change in weight between treatment groups, 
which is seen as a clinically meaningful weight change over 24 
weeks, and 6 kg as the estimate of standard deviation for NB 
treatment based on previously published data of NB in overweight 
and obese but otherwise healthy people over 6 months. Although 
the Apovian et al. study was 56 weeks in duration, the study had a 
midpoint analysis at 28 weeks which showed that almost all of the 
weight loss had already occurred, making this data useful for our 
power analysis. To achieve power=0.80, with a two-tailed 
significance level of 0.05, 30 subjects per treatment group will be 
required. 
All analyses will be performed on an intent-to-treat basis.  Analyses 
will be carried using a mixed model repeated-measures analysis of 
variance with fixed effects of visit, treatment group, baseline score, 
and visit x treatment and visit x baseline score interactions and 
random participant-specific intercepts and slopes.  Potential 
confounding variables will be included as covariates.  The effect of 
treatment on 24-week change from baseline will be determined by 
the estimated regression coefficient of the visit x group interaction 
term.  Differences between the treatment groups on categorical 
variables will be analyzed using the Fisher exact test or Chi-square 


test.  Independent sample t tests will be used to compare group 
differences on continuous variables.