Obese, Cigarette-smoking, Schizophrenia
Conditions
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.
Interventions
DRUGNaltrexone
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.
Placebo Naltrexone created and masked by the pharmacy to be used as a control.
DRUGBupropion
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 Bupropion created and masked by the pharmacy to be used as a control.
Sponsors
University of Massachusetts, Worcester
Shanghai Mental Health Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weight at 24 Weeks | baseline and 24 weeks | evaluate all participants' weight ，weight in kilograms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes From Baseline Craving for Nicotine Assessed by Visual Analog Scales (VAS) at 24 Weeks | baseline and 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. |
| Depression Status Assessed by Self-rating Depression Scale（SDS） | 24 weeks | 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. |
| Anxiety Status Assessed by Self-Rating Anxiety Scale（SAS） | 24 weeks | 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. |
| Clinical Symptoms Assessed by the Positive and Negative Syndrome Scale (PANSS) | 24 weeks | 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. |
| Waist Circumference | 24 weeks | evaluate all participants' waist circumference，waist circumference in centimeters |
| Change in Fasting Blood Glucose Levels | baseline and 24 weeks | — |
| Numbers of Participants Who Quit Smoking | 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 | — |
| Change in Fasting Insulin Levels | baseline and 24 weeks | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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.
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. | 11 |
| 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.
Placebo Naltrexone: Placebo Naltrexone created and masked by the pharmacy to be used as a control.
Placebo Bupropion: Placebo Bupropion created and masked by the pharmacy to be used as a control. | 11 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Naltrexone and Bupropion | Placebo Naltrexone and Bupropion | Total |
|---|---|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 5.7 | 54.1 years STANDARD_DEVIATION 8.4 | 54.2 years STANDARD_DEVIATION 7 |
| BMI | 26.8 kg/m^2 STANDARD_DEVIATION 2 | 28.5 kg/m^2 STANDARD_DEVIATION 3.7 | 27.6 kg/m^2 STANDARD_DEVIATION 3 |
| body weight | 74.7 kg STANDARD_DEVIATION 11.8 | 80.2 kg STANDARD_DEVIATION 11.8 | 77.5 kg STANDARD_DEVIATION 10.4 |
| breath CO level | 27.1 ppm STANDARD_DEVIATION 23.2 | 27.7 ppm STANDARD_DEVIATION 15.6 | 27.4 ppm STANDARD_DEVIATION 19.3 |
| fasting glucose | 5.5 mmol/l STANDARD_DEVIATION 1.1 | 5.5 mmol/l STANDARD_DEVIATION 2.2 | 5.5 mmol/l STANDARD_DEVIATION 1.7 |
| HbA1c | 6.1 percentage of HbA1c STANDARD_DEVIATION 0.6 | 6.3 percentage of HbA1c STANDARD_DEVIATION 1.8 | 6.2 percentage of HbA1c STANDARD_DEVIATION 1.2 |
| HDL | 0.9 mmol/l STANDARD_DEVIATION 0.2 | 0.8 mmol/l STANDARD_DEVIATION 0.1 | 0.9 mmol/l STANDARD_DEVIATION 0.2 |
| illness time duration | 29.8 years STANDARD_DEVIATION 4.6 | 25.9 years STANDARD_DEVIATION 9.1 | 27.9 years STANDARD_DEVIATION 7.8 |
| insulin | 106.8 pmol/l STANDARD_DEVIATION 65.8 | 84.5 pmol/l STANDARD_DEVIATION 60.4 | 95.7 pmol/l STANDARD_DEVIATION 62.5 |
| LDL | 2.8 mmol/l STANDARD_DEVIATION 0.8 | 2.4 mmol/l STANDARD_DEVIATION 0.9 | 2.6 mmol/l STANDARD_DEVIATION 0.8 |
| number of cigarettes smoked per week | 72.5 cigarettes per week STANDARD_DEVIATION 5.7 | 77.6 cigarettes per week STANDARD_DEVIATION 21.1 | 75.1 cigarettes per week STANDARD_DEVIATION 15.3 |
| Race/Ethnicity, Customized Han | 11 participants | 11 participants | 22 participants |
| Region of Enrollment China | 11 participants | 11 participants | 22 participants |
| Sex/Gender, Customized male | 11 participants | 11 participants | 22 participants |
| smoking craving | 6.3 units on a scale STANDARD_DEVIATION 1 | 7.0 units on a scale STANDARD_DEVIATION 1.4 | 6.6 units on a scale STANDARD_DEVIATION 1.3 |
| smoking time duration | 28.6 years STANDARD_DEVIATION 7.9 | 29.8 years STANDARD_DEVIATION 9.8 | 29.2 years STANDARD_DEVIATION 8.7 |
| Triglyceride | 2.3 mmol/l STANDARD_DEVIATION 1.1 | 1.5 mmol/l STANDARD_DEVIATION 0.6 | 1.9 mmol/l STANDARD_DEVIATION 0.9 |
| waist circumference | 94.9 cm STANDARD_DEVIATION 4.5 | 99.8 cm STANDARD_DEVIATION 6.8 | 97.4 cm STANDARD_DEVIATION 6.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 6 / 11 | 1 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 |
Outcome results
Primary
Change From Baseline in Weight at 24 Weeks
evaluate all participants' weight ，weight in kilograms
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Change From Baseline in Weight at 24 Weeks | 0.2 kilogram | Standard Deviation 5.3 |
| Placebo Naltrexone and Bupropion | Change From Baseline in Weight at 24 Weeks | -0.9 kilogram | Standard Deviation 3.1 |
Secondary
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.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Anxiety Status Assessed by Self-Rating Anxiety Scale（SAS） | 31.1 score on a scale | Standard Deviation 6.9 |
| Placebo Naltrexone and Bupropion | Anxiety Status Assessed by Self-Rating Anxiety Scale（SAS） | 28.8 score on a scale | Standard Deviation 4.2 |
Secondary
Change in Fasting Blood Glucose Levels
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Change in Fasting Blood Glucose Levels | 0.5 mmol/l | Standard Deviation 1.5 |
| Placebo Naltrexone and Bupropion | Change in Fasting Blood Glucose Levels | 1.0 mmol/l | Standard Deviation 1.6 |
Secondary
Change in Fasting HDL Cholesterol Levels
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Change in Fasting HDL Cholesterol Levels | 0.0 mmol/l | Standard Deviation 1.1 |
| Placebo Naltrexone and Bupropion | Change in Fasting HDL Cholesterol Levels | 0.0 mmol/l | Standard Deviation 0.1 |
Secondary
Change in Fasting Insulin Levels
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Change in Fasting Insulin Levels | 3.5 pmol/l | Standard Deviation 74.4 |
| Placebo Naltrexone and Bupropion | Change in Fasting Insulin Levels | 11.0 pmol/l | Standard Deviation 35.3 |
Secondary
Change in Fasting LDL Cholesterol
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Change in Fasting LDL Cholesterol | -0.4 mmol/l | Standard Deviation 0.7 |
| Placebo Naltrexone and Bupropion | Change in Fasting LDL Cholesterol | -0.2 mmol/l | Standard Deviation 0.7 |
Secondary
Change in Fasting Triglycerides Levels
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Change in Fasting Triglycerides Levels | -1.0 mmol/l | Standard Deviation 0.9 |
| Placebo Naltrexone and Bupropion | Change in Fasting Triglycerides Levels | -0.4 mmol/l | Standard Deviation 0.6 |
Secondary
Change in Ghrelin
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Change in Ghrelin | 352.2 pg/ml | Standard Deviation 296.6 |
| Placebo Naltrexone and Bupropion | Change in Ghrelin | 254.8 pg/ml | Standard Deviation 106.4 |
Secondary
Change in Glycosylated Hemoglobin
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Change in Glycosylated Hemoglobin | 0.05 percentage of hemoglobin | Standard Deviation 0.6 |
| Placebo Naltrexone and Bupropion | Change in Glycosylated Hemoglobin | 0.4 percentage of hemoglobin | Standard Deviation 1.1 |
Secondary
Change in Leptin
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Change in Leptin | 9.2 ng/ml | Standard Deviation 5.9 |
| Placebo Naltrexone and Bupropion | Change in Leptin | 10.6 ng/ml | Standard Deviation 7.1 |
Secondary
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.
Time frame: baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Changes From Baseline Craving for Nicotine Assessed by Visual Analog Scales (VAS) at 24 Weeks | -1.0 score on a scale | Standard Deviation 2.9 |
| Placebo Naltrexone and Bupropion | Changes From Baseline Craving for Nicotine Assessed by Visual Analog Scales (VAS) at 24 Weeks | -1.9 score on a scale | Standard Deviation 3.1 |
Secondary
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.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Clinical Symptoms Assessed by the Positive and Negative Syndrome Scale (PANSS) | 52.5 score on a scale | Standard Deviation 15 |
| Placebo Naltrexone and Bupropion | Clinical Symptoms Assessed by the Positive and Negative Syndrome Scale (PANSS) | 57.2 score on a scale | Standard Deviation 18.9 |
Secondary
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.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Depression Status Assessed by Self-rating Depression Scale（SDS） | 39.4 score on a scale | Standard Deviation 8.2 |
| Placebo Naltrexone and Bupropion | Depression Status Assessed by Self-rating Depression Scale（SDS） | 33.6 score on a scale | Standard Deviation 7.2 |
Secondary
Numbers of Participants Who Quit Smoking
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Naltrexone and Bupropion | Numbers of Participants Who Quit Smoking | 0 participants |
| Placebo Naltrexone and Bupropion | Numbers of Participants Who Quit Smoking | 0 participants |
Secondary
Waist Circumference
evaluate all participants' waist circumference，waist circumference in centimeters
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naltrexone and Bupropion | Waist Circumference | 98.6 cm | Standard Deviation 5.7 |
| Placebo Naltrexone and Bupropion | Waist Circumference | 101.3 cm | Standard Deviation 6.6 |