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Pharmacogenetics of Naltrexone for Stimulant Abuse

Primary Purpose

Substance Use Disorders, Methamphetamine Abuse

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Intranasal Methamphetamine

About this trial

This is an interventional basic science trial for Substance Use Disorders

Eligibility Criteria

21 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female age 21 to 50 years
DSM-5 criteria for mild-to-severe stimulant use disorder, along with intravenous, intranasal or smoked use of amphetamine-type stimulants in amounts equal to or greater than administered in the current study.
Able to give written informed consent to participate.
Females must be either post-menopausal, surgically sterilized, or using an acceptable method of contraception (double-barrier method like a condom with a spermicidal lubricant) to participate in this study.
Racially Caucasian or of European descent.

Exclusion Criteria:

Currently seeking treatment for a substance use disorder.
DSM-5 criteria for moderate-to-severe substance use disorders (except those involving cocaine, amphetamines and nicotine).
Psychiatric condition that may affect the participants' ability to provide informed consent (e.g., psychotic disorder), or make participation hazardous for the participant or study staff (e.g., severe depression/suicidality, or risk of violence).
Uncontrolled neurological, cardiovascular, and hepatic diseases, active tuberculosis, or any other disorder that might make administration of study medications hazardous.
Gastrointestinal or renal disease that would significantly impair absorption, metabolism or excretion of study drug, or require medication or medical treatment.
Current treatment with a psychotropic medication that in the physician's judgement would interfere with the study endpoints.
History of allergy, adverse reaction, or sensitivity to amphetamines.
Medical conditions that may make study participation hazardous:
- History of seizures or cardiac risk conditions (unstable angina, cardiac arrhythmias, chest pain, strong palpitations (subjectively defined as the feeling that the heart is beating too hard, too fast, skipping a beat, or fluttering).
- Elevated liver function tests (i.e., AST and ALT > 3 times the upper limit of normal).
- Impaired renal function (creatinine > 1.2).
- Hypertension (>140/90).
- Asthmatic symptoms within the past 3 years.

Sites / Locations

New York State Psychiatric Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Naltrexone 0 mg

Naltrexone 50 mg

Arm Description

This aim assess the effects of pretreatment with 0 mg of naltrexone on laboratory measures of the abuse potential of methamphetamine (30mg/70 kg).

This aim assess the effects of pretreatment with 50 mg of naltrexone on laboratory measures of the abuse potential of methamphetamine (30mg/70 kg).

Outcomes

Primary Outcome Measures

Methamphetamine Self-Administration

To assess the reinforcing effects of methamphetamine, participants complete a drug self-administration procedure. The outcome measure for this procedure is the number of operant responses (clicks on a mouse) participant are willing to make in order to receive drug (methamphetamine).

Secondary Outcome Measures

Positive Subjective Effects of Methamphetamine.

Participant ratings of methamphetamine "Liking," on a 100 mm visual analog scale. Participants are asked to indicate on a 100 mm line the extent to which they agree with the description of the drug provided. The 0 mm end of the line indicates "Not at All," while the 100 mm indicates "Extremely."

Full Information

NCT ID

NCT03226223

First Posted

July 20, 2017

Last Updated

November 8, 2020

Sponsor

New York State Psychiatric Institute

1. Study Identification

Unique Protocol Identification Number

NCT03226223

Brief Title

Pharmacogenetics of Naltrexone for Stimulant Abuse

Official Title

Using Pharmacogenetics to Better Evaluate Naltrexone for Treating Stimulant Abuse

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Completed

Study Start Date

September 15, 2016 (Actual)

Primary Completion Date

July 15, 2019 (Actual)

Study Completion Date

July 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

New York State Psychiatric Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This investigation will be the first study assessing genetic modulation of naltrexone's NTX effects upon the abuse liability of a stimulant drug (methamphetamine). The study team will assess the ability of oral NTX to block the reinforcing and positive subjective effects of intranasal (IN) methamphetamine (30mg/70kg). This investigation could identify an important Gene x Pharmacological interaction, contributing to the personalization of stimulant abuse pharmacotherapy.

Detailed Description

A recent meta-analysis concluded that the OPRM1 A118G SNP (rs1799971) significantly moderates the treatment efficacy of Naltrexone (NTX) in treating alcohol abuse, increasing the treatment efficacy by over 2-fold among G-allele carriers (AG/GG). The proposed application would be the first to investigate the moderating effect of this genotype in the efficacy of NTX to treat stimulant abuse. More specifically, the study team proposes to investigate the interaction between NTX and intranasal (IN) methamphetamine (30mg/70kg). Participants who meet DSM criteria for mild-to-severe stimulant use disorder (N=up to 70) will complete 4 testing sessions where drug effects are tested following pretreatment with NTX (0, 50 mg). Naltrexone pretreatment effects upon the abuse liability of IN methamphetamine will be assessed using self-report measurements of positive subjective effects and drug self-administration. Medication effects on these validated predictors of abuse potential will be compared between A118G A allele homozygotes (AA) and G-allele carriers (AG/GG; an anticipated 25% of the total sample), in order to assess genetic moderation of treatment outcome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Substance Use Disorders, Methamphetamine Abuse

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Model Description

Participants will complete two testing sessions in which the effects of oral naltrexone (0 mg & 50 mg) will be tested in combination with intranasal methamphetamine. Participants will complete two testing sessions (naltrexone 0 mg + Methamphetamine & naltrexone 50 mg + methamphetamine), in randomized order.

Masking

Participant

Masking Description

Participants and study staff conducting the lab sessions will be blinded to the treatment condition (i.e., naltrexone 0 mg or 50 mg)

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Naltrexone 0 mg

Arm Type

Placebo Comparator

Arm Description

This aim assess the effects of pretreatment with 0 mg of naltrexone on laboratory measures of the abuse potential of methamphetamine (30mg/70 kg).

Arm Title

Naltrexone 50 mg

Arm Type

Experimental

Arm Description

This aim assess the effects of pretreatment with 50 mg of naltrexone on laboratory measures of the abuse potential of methamphetamine (30mg/70 kg).

Intervention Type

Drug

Intervention Name(s)

Intranasal Methamphetamine

Intervention Description

Intranasal Methamphetamine HCL administered at a dose of 30mg per 70 kg of the participants' body weight)

Primary Outcome Measure Information:

Title

Methamphetamine Self-Administration

Description

Time Frame

1 day.

Secondary Outcome Measure Information:

Title

Positive Subjective Effects of Methamphetamine.

Description

Time Frame

1 day

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female age 21 to 50 years DSM-5 criteria for mild-to-severe stimulant use disorder, along with intravenous, intranasal or smoked use of amphetamine-type stimulants in amounts equal to or greater than administered in the current study. Able to give written informed consent to participate. Females must be either post-menopausal, surgically sterilized, or using an acceptable method of contraception (double-barrier method like a condom with a spermicidal lubricant) to participate in this study. Racially Caucasian or of European descent. Exclusion Criteria: Currently seeking treatment for a substance use disorder. DSM-5 criteria for moderate-to-severe substance use disorders (except those involving cocaine, amphetamines and nicotine). Psychiatric condition that may affect the participants' ability to provide informed consent (e.g., psychotic disorder), or make participation hazardous for the participant or study staff (e.g., severe depression/suicidality, or risk of violence). Uncontrolled neurological, cardiovascular, and hepatic diseases, active tuberculosis, or any other disorder that might make administration of study medications hazardous. Gastrointestinal or renal disease that would significantly impair absorption, metabolism or excretion of study drug, or require medication or medical treatment. Current treatment with a psychotropic medication that in the physician's judgement would interfere with the study endpoints. History of allergy, adverse reaction, or sensitivity to amphetamines. Medical conditions that may make study participation hazardous: History of seizures or cardiac risk conditions (unstable angina, cardiac arrhythmias, chest pain, strong palpitations (subjectively defined as the feeling that the heart is beating too hard, too fast, skipping a beat, or fluttering). Elevated liver function tests (i.e., AST and ALT > 3 times the upper limit of normal). Impaired renal function (creatinine > 1.2). Hypertension (>140/90). Asthmatic symptoms within the past 3 years.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jermaine Jones, PhD

Organizational Affiliation

NYSPI

Official's Role

Principal Investigator

Facility Information:

Facility Name

New York State Psychiatric Institute

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Pharmacogenetics of Naltrexone for Stimulant Abuse

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