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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation N40D

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 6 clinical trials

Clinical Trials


1 Injectable Naltrexone Treatment of Alcohol Dependence in Serious Mental Illness (SMI): An Open Prospective Pilot Trial

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 ---

Primary Outcomes

Measure: feasibility: number recruited, visits attended

Secondary Outcomes

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

Measure: alcohol use: self-report, biological measures, level of craving.

Measure: psychiatric functioning

Measure: neuropsychological functioning

2 Defining an Endopheneotype for Alcohol Treatment With Naltrexone

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 ---

Primary Outcomes

Description: Change from baseline to peak cortisol response, during the 2nd alcohol challenge session, subjective response as measured by Biphasic Alcohol Effects Scale: Total Mood. Biphasic Alcohol Effects Scale: Total Mood: minimum = 0, maximum = 106, higher scores indicate better outcomes.

Measure: Biphasic Alcohol Effects Scale:Total Mood

Time: during 2nd alcohol challenge session

Secondary Outcomes

Description: Change from baseline to peak cortisol response during the 2nd alcohol challenge session, objective response as measured by Adrenocorticotropic hormone (ACTH).

Measure: Adrenocorticotropic Hormone (ACTH) Levels

Time: during 2nd alcohol challenge session

3 Mu-Opioid Receptor Genetic Polymorphism and the Duration of Intrathecal Fentanyl Labor Analgesia. Mu-Opioid Receptor Genetic Polymorphism and the Efficacy of Postoperative Intrathecal Morphine Analgesia

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 ---

Primary Outcomes

Description: Time from intrathecal drug administration to request for analgesia either in laboring women of after cesarean delivery

Measure: Duration of Intrathecal Fentanyl Analgesia

Time: Time (0-1440 minutes) to first analgesia request

Description: Time until request for supplemental analgesia following intrathecal morphine/fentanyl for cesarean delivery

Measure: Duration of Intrathecal Analgesia Following Cesarean Delivery

Time: 0 to 72 hours following cesarean delivery

Description: Visual analog pain scale (0 to 100) at 1st request for supplemental analgesia

Measure: Visual Analog Pain Scale (0 to 100) at Analgesia Request Following Intrathecal Intervention

Time: VAS at analgesia request

Secondary Outcomes

Description: Severity of pruritus during labor analgesia

Measure: Severity of Pruritus Following Fentanyl

Time: Labor analgesia

Description: Subjects reporting pruritus in the first 24 hours post cesarean delivery

Measure: Subjects With Pruritus at 24 Hours Post Morphine

Time: 24 hours post cesarean delivery

4 Pharmacogenetic Response to Naltrexone for Alcohol Dependence

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 ---

Primary Outcomes

Measure: Clinical Response to Naltrexone, as Measured by a Reduction in the Percent Days of Heavy Drinking Days (as Defined by >5 Drinks/Day for Males; >4 for Females) During the 12 Weeks of the Trial.

Time: 12 weeks

5 Pharmacogenetic Investigation of Naltrexone

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 ---

Primary Outcomes

Description: On day 4 of each study medication period, participants completed a cigarette choice procedure where the subject is asked to take 4 puffs from a nicotinized (nicotine-containing) or a denicotinized (no nicotine) cigarette every 30 minutes for 2 hours (maximum of 24 puffs). The outcome variable is the number of nicotine cigarette choices or puffs out of 24 total puffs during these cigarette choice procedures. Subjects who had the A/A genotype took an average of 18.5 puffs from the nicotine-containing cigarettes. Subjects with the A/G or G/G genotypes took an average of 16.2 puffs from the nicotine-containing cigarettes.

Measure: Number of Nicotine Cigarette Choices Taken During the Cigarette Choice Procedure.

Time: 2 hours

6 Optimizing 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.

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 ---

Primary Outcomes

Description: Alcohol Urge Questionnaire (AUQ) is used to assess subjective experiences of craving for alcohol. It consists of 8 items, each rated on a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). A summary score is used at each assessment time point. The AUQ was administered at baseline and three levels of breath alcohol concentration: 0.02 g/dl. 0.04, g/dl, and 0.06 g/dl.

Measure: Subjective Response - Craving for Alcohol

Time: The AUQ was administered across a period of approximately 1.5 hours.

Description: The Biphasic Alcohol Effects Scale (BAES) Stimulant Subscale consists of 14 items designed to capture the stimulant effects of alcohol, rated on an 11-point scale (0 = not at all. 10 = extremely). Total score for the stimulant subscale ranges from 0-70.

Measure: Subjective Response - Stimulation

Time: The BAES Stimulant Subscale was administered at baseline and three levels of breath alcohol concentration: 0.2 g/dl. 0.04, g/dl, and 0.06 g/dl taking place within approximately 1.5 hours

Description: The Biphasic Alcohol Effects Scale (BAES) Sedation Subscale consists of 14 items designed to capture the sedating effects of alcohol, rated on an 11-point scale (0 = not at all. 10 = extremely). Total score for the sedation subscale ranges from 0-70.

Measure: Subjective Response - Sedation

Time: The BAES Sedation Subscale was administered at baseline and three levels of breath alcohol concentration: 0.2 g/dl. 0.04, g/dl, and 0.06 g/dl taking place within approximately 1.5 hours

Description: Alcohol taste cues task for functional magnetic resonance imaging (fMRI). Region of Interest (ROI) were atomically defined using the Harvard-Oxford atlas in standard Montreal Neurological Institute (MNI) space, which were transformed into individual participants' native space using Functional Magnetic Resonance Imaging of the Brain Software Library (FSL). Contrast estimates are for Alc > Water cue, and are arbitrary units.

Measure: Neural Response to Alcohol Cues

Time: During the alcohol cue exposure fMRI paradigm which is expected to last 45 minutes

Secondary Outcomes

Description: Total number of drinks consumed during the alcohol self-administration task

Measure: Alcohol Self-administration - Number of Drinks

Time: Alcohol self-administration period was 1 hour long


HPO Nodes