The overall goal of this project is to improve the treatment of alcohol dependence in patients with serious mental illness (SMI). SMI for this study is defined as any patient with any of the following diagnoses: schizophrenia, schizoaffective disorder, and bipolar type I or type II disorder. Alcohol and other substance use disorders (SUDs) are common among individuals with SMI. SUD comorbidity is associated with many adverse consequences. However, to date, few reports have addressed the efficacy of pharmacological treatments for SUDs in this population. Naltrexone pharmacotherapy is an effective treatment for alcohol dependence, but it has not been systematically applied to the care of patients with SMI. The primary aim of this study is to determine the feasibility of long-acting injectable naltrexone administration in a clinical trial in patients with SMI who also have a diagnosis of alcohol dependence. Secondary aims include providing a preliminary assessment of the tolerability and safety of long-acting injectable naltrexone in patients with SMI who also have a diagnosis of alcohol dependence. An additional aim is to provide a preliminary assessment of the efficacy of long-acting injectable naltrexone in reducing alcohol use from baseline levels.

NCT00453609

Conditions

1. Schizophrenia
2. Schizoaffective Disorder
3. Bipolar Disorder
4. Alcohol Dependence

Interventions

1. Drug: long-lasting injectable naltrexone

MeSH:Disease Alcoholism Schizophrenia Bipolar Disorder Psychotic Disorders

HPO:Bipolar affective disorder Mania Psychosis Schizophrenia

genetic testing to examine functional polymorphism (Asn40Asp) differences in the subjects' μ-opioid receptors (OPRM1). --- Asn40Asp ---

Study outcomes consist of self-report and biological measures of alcohol use; measures of psychiatric symptom severity and neurocognitive functioning; and genetic testing to examine functional polymorphism (Asn40Asp) differences in the subjects' μ-opioid receptors (OPRM1), which may predict response to naltrexone treatment. --- Asn40Asp ---

This is a study involving treatment for alcohol dependence among males of European or Asian decent. The ultimate aim of this line of investigation is to further establish a genetic link between alcohol dependence and treatment by defining an endophenotype associated with treatment response. The study consists of two inpatient alcohol challenge sessions with treatment using random assignment to either naltrexone or placebo.

NCT00817089

Conditions

1. Alcoholism

Interventions

1. Drug: Placebo Oral Tablet
2. Drug: Naltrexone

MeSH:Alcoholism

Recent work at our center provides evidence that the mu-opioid receptor (OPRM1) gene polymorphism A118G (Asn40Asp) imparts a significant change in treatment response. --- A118G --- --- Asn40Asp ---

Pharmacogenetics has allowed clinicians to identify associations between an individual's genetic profile and his/her response to drugs. The A118G (c.188A>G)is a single nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1). The mutated protein, N40D, appears to increase the binding affinity and potency of beta-endorphin approximately 3-fold. Individuals carrying the variant receptor gene (A118G) may show differences in some of the functions mediated by beta-endorphin action at the altered OPRM1. Combined spinal-epidural (CSE) analgesia is a commonly utilized technique for labor analgesia. Analgesia is initiated with the intrathecal administration of a lipid-soluble opioid (e.g. fentanyl), sometimes combined with a local anesthetic. The mean (± SD) duration of analgesia after intrathecal fentanyl 25 microgram was 89 ± 43 min. The ED50 of intrathecal fentanyl for labor analgesia varies between 14 microgram to 18.2 microgram. The wide variability in the duration of analgesia, as was well the differences in ED50 may result from differences known to affect labor pain (e.g., ethnicity, parity, stage of labor). Another possible explanation for the differences in opioid requirements and duration, as well as incidence of side effects such as itching and nausea/vomiting, is that opioid responsiveness is determined by genetic variability of the µ-opioid receptor. The ED50 for intrathecal fentanyl labor analgesia was significantly lower for parturients carrying the A118G variant of the mu-opioid receptor, compared to parturients with the A118 wild type receptor. The purpose of this study is to determine whether polymorphism at nucleotide 118 of OPRM1 influences the duration of intrathecal opioid (fentanyl) labor analgesia, and intrathecal opioid (morphine) postoperative analgesia.

NCT00418015

Conditions

1. Labor Pain
2. Post-cesarean Delivery

Interventions

1. Procedure: Blood Draw

MeSH:Labor Pain

The mutated protein, N40D, appears to increase the binding affinity and potency of beta-endorphin approximately 3-fold. --- N40D ---

The aims of the study are to test for treatment outcome differences in alcohol dependent subjects randomly assigned to 12 weeks of treatment with NTX (50mg/day) or placebo among those with one or two copies of the Asp40 allele of the mu-opioid receptor compared to those homozygous for the Asn40 allele. Thus, the design of the study is a 2X2 cell double-blind randomization to NTX or placebo stratified by genotype. To meet these aims, 150 alcohol dependent outpatients with one or two copies of the Asp40 variant of the mu-opioid receptor and 190 subjects homozygous for the Asn40 variant will be recruited across the four participating sites.

NCT00831272

Conditions

1. Alcohol Dependence

Interventions

1. Drug: naltrexone
2. Drug: Placebo

MeSH:Alcoholism

Recent work at our center provides evidence that the mu-opioid receptor (OPRM1) gene polymorphism A118G (Asn40Asp) imparts a significant change in treatment response. --- A118G --- --- Asn40Asp ---

Based upon these very promising findings, the aim of this study is to examine prospectively the interaction between a functional polymorphism of the mu-opioid receptor (A+118G (Asn40Asp)) and response to treatment with naltrexone. --- Asn40Asp ---

Despite preclinical evidence supporting the role of the endogenous opioid system in the reinforcing effects of nicotine, the efficacy of the opioid antagonist naltrexone (NTX) as a tobacco dependence treatment remains unresolved. Research is needed to identify those smokers for whom NTX will have the strongest beneficial effects on smoking behavior. The research bridges existing knowledge of genetic, pharmacologic, and behavioral responses to nicotine, and translates this knowledge to treatment for tobacco dependence. The immediate goal was to test whether genetic variation in the mu-opioid receptor gene predicts the effects of naltrexone (NTX) on nicotine reinforcement.

NCT00270231

Conditions

1. Tobacco Dependence

Interventions

1. Drug: Naltrexone
2. Drug: Placebo

MeSH:Tobacco Use Disorder

A key question was whether smokers differ in their responses based on the mu opioid receptor gene (OPRM1) Asn40Asp (A118G) variant. --- Asn40Asp ---

This study will elucidate the pharmacogenetic effects of the Asn40Asp SNP of the OPRM1 gene on biobehavioral and neural markers of response to naltrexone in individuals of East Asian descent, an ethnic group most likely to express the positive predictive allele.

NCT02026011

Conditions

1. Alcohol Use Disorder

Interventions

1. Drug: Naltrexone
2. Drug: Placebo

MeSH:Alcoholism Alcohol Drinking

Naltrexone for Individuals of East Asian Descent This study will elucidate the pharmacogenetic effects of the Asn40Asp SNP of the OPRM1 gene on biobehavioral and neural markers of response to naltrexone in individuals of East Asian descent, an ethnic group most likely to express the positive predictive allele. --- Asn40Asp ---

The most widely studied polymorphism of the OPRM1 gene is the Asn40Asp single nucleotide polymorphism (SNP), a functional mutation thought to affect receptor activity such that the Asp40 variant binds β-endorphin three times stronger than the Asn40 allele. --- Asn40Asp ---

This pilot study also found support for a gene dose-response, such that Asp40Asp individuals showed greater NTX responsivity than those with the Asn40Asp genotype. --- Asn40Asp ---

This study seeks to build upon these preliminary findings by testing heavy drinkers of East Asian descent across three OPRM1 genotypes (Asn40Asn, n = 30; Asn40Asp, n = 30, and Asp40Asp, n = 30). --- Asn40Asp ---

This study will elucidate the pharmacogenetic effects of the Asn40Asp SNP of the OPRM1 gene on biobehavioral and neural markers of response to naltrexone in individuals of Asian descent, an ethnic group most likely to express the positive predictive allele (Asp40). --- Asn40Asp ---