Clinical trial NCT01866098: Naltrexone for Antipsychotic-Induced Weight Gain
Official title: Naltrexone for Antipsychotic-Induced Weight Gain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Schizoaffective Disorder
Schizophreniform Disorder
Bipolar Disorder
Severe Major Depression With Psychotic Features
Keywords: antipsychotic
severe mental illness
weight loss
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2013-05-31
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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").

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Age 18 to 75
* Meet Diagnostic \& Statistical Manual - 4 (DSM-IV) criteria for schizophrenia, schizoaffective disorder, bipolar disorder, major depression, or another psychotic disorder based on Structured Clinical Interview for the DSM-IV (SCID) interview
* Body Mass Index (BMI) of 28 and over
* On a stable dose of antipsychotic medication; i.e. at least one month with no dose change, and three months from an antipsychotic switch
* Deemed to be symptomatically stable by the clinical staff in the last two months
* Over 7% total body weight increase on antipsychotics for subjects within first year of illness

Exclusion Criteria:

* Meet criteria for current opiate abuse or dependence (confirmed by positive urine drug screen for opiates or, if suspected by study doctor via patient history and or suspicion of occult opiate use, a naloxone challenge will be performed.)
* Current history of dementia, mental retardation
* Not capable of giving informed consent for participation in the study
* Women who are pregnant or breast-feeding
* Physical conditions affecting body weight (e.g. Cushing's disease, polycystic ovary syndrome) Diabetes Mellitus (defined as prescribed an anti-diabetic medication for diabetes or a hemoglobin A1c level \> 7 confirmed by primary care physician at screening)
* Severe liver dysfunction, (serum aminotransferases greater than three times normal), acute infectious hepatitis, liver failure.

Primary outcomes:
measure: Change in Weight From Baseline
timeFrame: Baseline and 52 weeks
measure: Percent of Subjects Who Lost More Than 5% of Body Weight From Baseline
timeFrame: 52 weeks
Secondary outcomes:
measure: Changes in Fasting Glucose From Baseline
timeFrame: Baseline and 52 weeks
measure: Changes in Glycosylated Hemoglobin (HbA1c) From Baseline
timeFrame: Baseline and 52 weeks
measure: Changes in Insulin From Baseline
timeFrame: Baseline and 52 weeks
measure: Changes in Total Cholesterol From Baseline
timeFrame: Baseline and 52 weeks
measure: Changes in HDL From Baseline
timeFrame: Baseline and 52 weeks
measure: Changes in LDL From Baseline
timeFrame: Baseline and 52 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Connecticut Mental Health Center
state: Connecticut
Study officials:
affiliation: Yale University
name: Cenk Tek, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tek C, Guloksuz S, Srihari VH, Reutenauer EL. Investigating the safety and efficacy of naltrexone for anti-psychotic induced weight gain in severe mental illness: study protocol of a double-blind, randomized, placebo-controlled trial. BMC Psychiatry. 2013 Jun 27;13:176. doi: 10.1186/1471-244X-13-176.