An interventional study of Naltrexone and Placebo in Schizophrenia, Schizoaffective Disorder and Schizophreniform Disorder, sponsored by Yale University. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-10-01.
Sponsored by Yale University · Not applicable, Interventional, and Treatment
This study is designed to look at the effects of naltrexone on weight loss in individuals treated with antipsychotic medications. Naltrexone is an FDA approved medication for the management of alcohol dependence and drug dependence, but has not been fully evaluated for its effect on weight loss in individuals with severe mental illness (i.e. schizophrenia, schizoaffective disorder, bipolar disorder etc.) The purpose of this study is to find out how effective two different doses of oral naltrexone is on reducing body weight when compared to placebo (an inactive substance or "sugar pill").
Persons with severe mental illness (SMI) die, on average, 25 years earlier than the general population1. Most of this early mortality can be attributed to cardiovascular disease (CVD) and diabetes mellitus (DM), which are directly related to obesity. Obesity is a leading cause of preventable death in the United States, second only to smoking. The physical health of patients has become a major focus of schizophrenia care, as recent decades have seen immense gains in symptom control and community integration. There is an urgent need for the development of interventions that address the obesity crisis in schizophrenia.
Patients treated with antipsychotic medications have been shown to have a preference for diets high in fat and sugar. Patients with schizophrenia typically seek behaviors that increase dopamine mediated reward in the brain such as smoking and substance use, both of which occur more often in this group than the general population. The system might require intact dopamine and opioid function.
Naltrexone is an oral agent that competitively antagonizes all known opioid receptors in the brain. Human studies with naltrexone were completed in individuals with different illnesses, including schizophrenia, and have been shown to be a safe and easy agent to use. It is shown to decrease craving in alcoholics and is approved by the FDA for the treatment of alcohol dependence. Naltrexone is reported to decrease craving for other substances of abuse, like nicotine. Furthermore, it has been shown to prevent secondary weight gain due to cessation of cigarette smoking at low (25mg and 50 mg), but not higher doses. Naltrexone has been tested in human feeding studies, and has been shown to reduce both the quantity of food eaten and the choice of palatable foods.
Subjects will be randomized to either 25, 50 or 0mg of Naltrexone and will take the study medication daily for 52 weeks. Subjects will be seen weekly for the first 4 weeks of the study, thereafter they will be seen on a bi-weekly (every other week) basis to be assessed (i.e. weight, side effect check, paper questionnaires) throughout the remaining 48 weeks of treatment.
The purpose of this study is to determine the efficacy of two doses of naltrexone (25mg \& 50mg) versus placebo for weight and health risk reduction in 144 obese individuals with severe mental illness treated with an antipsychotic medication.
405 studies on the registry are indexed under Weight Gain; 52 are open to participants now.
This study's enrollment of 144 is above the median of 83 across 324 interventional studies indexed under Weight Gain.
Browse Weight Gain studies →Yale University is the lead sponsor of 1,724 studies on the registry; 298 are open to participants now.
Of its 210 completed or terminated interventional studies of FDA-regulated products, 126 (60%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Oral Naltrexone 50mg capsule taken once daily for 52 weeks
Drug: Naltrexone
Oral placebo capsule taken once daily for 52 weeks
Drug: Placebo
Oral Naltrexone 25mg capsule taken once daily for 52 weeks
Drug: Naltrexone
25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.
Also known as: Revia
Change in Weight From Baseline
Weight (kilograms; kg) will be measured at each assessment and change in weight will be determined at study endpoint.
Time frame: Baseline and 52 weeks
Percent of Subjects Who Lost More Than 5% of Body Weight From Baseline
Body Mass Index will be calculated at each assessment and change over time will be assessed at endpoint.
Time frame: 52 weeks
Changes in Fasting Glucose From Baseline
Fasting glucose will be collected over the course of participation and changes will be evaluated at study endpoint.
Time frame: Baseline and 52 weeks
Changes in Glycosylated Hemoglobin (HbA1c) From Baseline
Glycosylated hemoglobin (HbA1c) will be collected over the course of participation and changes will be evaluated at study endpoint.
Time frame: Baseline and 52 weeks
Changes in Insulin From Baseline
Insulin will be collected over the course of participation and changes will be evaluated at study endpoint.
Time frame: Baseline and 52 weeks
Changes in Total Cholesterol From Baseline
Total Cholesterol will be collected over the course of participation and changes will be evaluated at study endpoint.
Time frame: Baseline and 52 weeks
Changes in HDL From Baseline
High-density lipoprotein (HDL) will be collected over the course of participation and changes will be evaluated at study endpoint.
Time frame: Baseline and 52 weeks
Changes in LDL From Baseline
Low-density lipoprotein (HDL) will be collected over the course of participation and changes will be evaluated at study endpoint.
Time frame: Baseline and 52 weeks
| Milestone | Placebo | Naltrexone 25mg | Naltrexone 50mg |
|---|---|---|---|
| Started | 51 | 47 | 46 |
| Completed | 32 | 20 | 25 |
| Not completed | 19 | 27 | 21 |
| Withdrew: Lost to follow-up | 11 | 18 | 13 |
| Withdrew: Physician decision | 0 | 1 | 2 |
| Withdrew: Adverse event | 1 | 5 | 4 |
| Withdrew: Protocol violation | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 2 | 0 |
| Withdrew: Unrelated hospitalization | 2 | 0 | 1 |
| Withdrew: Non-compliance | 1 | 0 | 1 |
| Withdrew: Pregnancy | 2 | 0 | 0 |
| Withdrew: Death | 0 | 1 | 0 |
Weight (kilograms; kg) will be measured at each assessment and change in weight will be determined at study endpoint.
| kg | Placebo | Naltrexone 25mg | Naltrexone 50mg |
|---|---|---|---|
| Change in Weight From Baseline | -0.16 ± 1.78 | 0.69 ± 2.22 | -0.95 ± 2.06 |
Body Mass Index will be calculated at each assessment and change over time will be assessed at endpoint.
| Participants | Placebo | Naltrexone 25mg | Naltrexone 50mg |
|---|---|---|---|
| Percent of Subjects Who Lost More Than 5% of Body Weight From Baseline | 10 | 4 | 9 |
Fasting glucose will be collected over the course of participation and changes will be evaluated at study endpoint.
| mg/dL | Placebo | Naltrexone 25mg | Naltrexone 50mg |
|---|---|---|---|
| Changes in Fasting Glucose From Baseline | 8.2 ± 2.6 | 4.6 ± 3.2 | -0.4 ± 2.9 |
Glycosylated hemoglobin (HbA1c) will be collected over the course of participation and changes will be evaluated at study endpoint.
| mg/dL | Placebo | Naltrexone 25mg | Naltrexone 50mg |
|---|---|---|---|
| Changes in Glycosylated Hemoglobin (HbA1c) From Baseline | -0.007 ± 0.11 | -0.061 ± 0.15 | 0.060 ± 0.39 |
Insulin will be collected over the course of participation and changes will be evaluated at study endpoint.
| mg/dL | Placebo | Naltrexone 25mg | Naltrexone 50mg |
|---|---|---|---|
| Changes in Insulin From Baseline | 6.45 ± 4.89 | 0.45 ± 6.23 | 2.16 ± 5.55 |
Total Cholesterol will be collected over the course of participation and changes will be evaluated at study endpoint.
| mg/dL | Placebo | Naltrexone 25mg | Naltrexone 50mg |
|---|---|---|---|
| Changes in Total Cholesterol From Baseline | -1.16 ± 5.12 | 1.52 ± 6.41 | -3.02 ± 5.72 |
High-density lipoprotein (HDL) will be collected over the course of participation and changes will be evaluated at study endpoint.
| mg/dL | Placebo | Naltrexone 25mg | Naltrexone 50mg |
|---|---|---|---|
| Changes in HDL From Baseline | 0.04 ± 1.73 | 0.79 ± 2.19 | 0.36 ± 1.93 |
Low-density lipoprotein (HDL) will be collected over the course of participation and changes will be evaluated at study endpoint.
| mg/dL | Placebo | Naltrexone 25mg | Naltrexone 50mg |
|---|---|---|---|
| Changes in LDL From Baseline | -10.87 ± 4.47 | 1.14 ± 5.46 | -4.40 ± 4.91 |
Collected over Up to 52 weeks.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 0/51 (0%) | 0/51 (0%) | 35/51 (68.6%) |
| Naltrexone 25mg | 1/47 (2.1%) | 1/47 (2.1%) | 33/47 (70.2%) |
| Naltrexone 50mg | 0/46 (0%) | 0/46 (0%) | 35/46 (76.1%) |
| Event | Placebo | Naltrexone 25mg | Naltrexone 50mg |
|---|---|---|---|
| Cocaine OverdoseGeneral disorders | 0/51 | 1/47 | 0/46 |
| Event | Placebo | Naltrexone 25mg | Naltrexone 50mg |
|---|---|---|---|
| NauseaGastrointestinal disorders | 21/51 | 20/47 | 19/46 |
| DizzinessNervous system disorders | 8/51 | 8/47 | 15/46 |
| HeadacheNervous system disorders | 15/51 | 11/47 | 13/46 |
| Reduced sleepNervous system disorders | 7/51 | 3/47 | 10/46 |
| DiarrheaGastrointestinal disorders | 11/51 | 6/47 | 7/46 |
| ConstipationGastrointestinal disorders | 11/51 | 10/47 | 7/46 |
| Stomach painGastrointestinal disorders | 0/51 | 2/47 | 7/46 |
| Reduced salivationGastrointestinal disorders | 6/51 | 1/47 | 1/46 |
| Asthenia/FatigabilityGeneral disorders | 2/51 | 2/47 | 5/46 |
| Sleepiness/SedationNervous system disorders | 3/51 | 5/47 | 2/46 |
| Age, Continuous(years) | Placebo | Naltrexone 25mg | Naltrexone 50mg | Total |
|---|---|---|---|---|
| Mean | 42.8 ± 12.8 | 45.0 ± 11.5 | 43.0 ± 14.2 | 43.6 ± 12.8 |
| Sex: Female, Male(Participants) | Placebo | Naltrexone 25mg | Naltrexone 50mg | Total |
|---|---|---|---|---|
| Female | 30 | 22 | 25 | 77 |
| Male | 21 | 25 | 21 | 67 |
| Race/Ethnicity, Customized(Participants) | Placebo | Naltrexone 25mg | Naltrexone 50mg | Total |
|---|---|---|---|---|
| White/Caucasian | 18 | 16 | 27 | 61 |
| African American | 24 | 28 | 16 | 68 |
| Other | 9 | 3 | 3 | 15 |
| Region of Enrollment(participants) | Placebo | Naltrexone 25mg | Naltrexone 50mg | Total |
|---|---|---|---|---|
| United States | 51 | 47 | 46 | 144 |
| Body Mass Index (BMI)(weight in kg/ height m^2) | Placebo | Naltrexone 25mg | Naltrexone 50mg | Total |
|---|---|---|---|---|
| Mean | 39.1 ± 7.3 | 37.1 ± 5.7 | 38.9 ± 11.4 | 38.4 ± 8.4 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — All de-identified data resulting from this award involving human subjects will be submitted to the NIMH Data Archive (NDA) - National Database for Clinical Trials Related to Mental Illness (NDCT) The Principal Investigator will work with NDA support staff to plan an appropriate data submission schedule and provide information on the steps for submission and sharing of data. Communication of this data sharing plan to appropriate research staff to ensure the timely submission of data. All human subject data provided will include an NDA Global Unique Identifier (GUID) and will not include personally identifiable information (PII). Analyzed data will be submitted no later than the time of publication. Even if a publication focuses on only part of an analyzed dataset, the entire analyzed dataset will be submitted when the first paper is published. All data made available for public use via NDA will be de-identified data.
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Yale University