Glutamatergic Modulation to Facilitate Naltrexone Initiation in Opioid Dependence

NCT02437344 | Completed Phase 2 Results DMC

• 1 other identifier: #7057
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Opioid dependence is a substantial problem associated with significant morbidity and mortality. Extended-release naltrexone has been found effective at reducing opioid use and maintaining abstinence, but its use has been limited by the difficulties encountered with treatment initiation, which involves detoxification from opioids and oral naltrexone titration. Improving the likelihood of a successful transition to naltrexone is therefore an important public health goal. N-methyl-D-aspartate receptor (NMDA) antagonism has been found to alleviate the signs and symptoms of withdrawal from opioids, as well as to address adaptations associated with chronic opioid use, such as opioid-induced hyperalgesia (increased pain sensitivity). These benefits may persist for at least 72 hours after a single dose. NMDA antagonism may therefore facilitate a rapid transition to naltrexone by reducing discomfort, improving motivation, and ameliorating adaptations associated with drug dependence, such as craving and arousal. The purpose of this trial is to assess the feasibility of NMDA antagonist-assisted naltrexone initiation in opioid dependent individuals. After administration of extended-release naltrexone, participants will be followed for 4 weeks, and transitioned to appropriate care subsequently (oral naltrexone, extended-release naltrexone).

Conditions

Opioid Dependence

Outcome Measures

Primary Outcomes (1)

• Successful Naltrexone Initiation

  The proportion of participants enrolled in the trial and receiving the infusion to receive XR-NTX

  2 weeks

Secondary Outcomes (1)

• Withdrawal: Subjective Opioid Withdrawal Scale (SOWS) Scores at Baseline and Administered Subsequently

  4 days

Study Arms (1)

CI-581aa

EXPERIMENTAL

CI-581aa will be administered 24 hours after last opioid use, and followed by naltrexone dosing

Drug: CI-581aa; Drug: Naltrexone titration and XR-NTX initiation

Interventions

CI-581aa DRUG

92 minute infusion of CI-581aa

Also known as: NMDA antagonist

CI-581aa

Naltrexone titration and XR-NTX initiation DRUG

participants will be provided a titration of naltrexone that culminates in the injection of XR-NTX

Also known as: naltrexone

CI-581aa

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Active opioid dependence, with at least one positive utox result; no history of opioid overdose; and not currently using methadone or buprenorphine
• Physically healthy
• No adverse reactions to study medications
• years of age
• Capacity to consent and comply with study procedures
• Seeking treatment

You may not qualify if:

• Meets DSM IV criteria for current major depression, bipolar disorder, schizophrenia, any psychotic illness, including substance-induced psychosis, and current substance-induced mood disorder with HAMD \> 12.
• Physiological dependence on another substance requiring medical management, such as alcohol or benzodiazepines, excluding caffeine, nicotine, and cannabis
• Pregnant or interested in becoming pregnant
• Delirium, Dementia, Amnesia, Cognitive Disorders, or dissociative disorders
• Current suicide risk or a history of suicide attempt within the past 2 years
• On psychotropic or other medication whose effect could be disrupted by participation in the study
• Recent history of significant violence (past 2 years).
• Heart disease as indicated by history, abnormal ECG, previous cardiac surgery.
• Unstable physical disorders which might make participation hazardous such as end-stage AIDS, hypertension (\>140/90), anemia, active hepatitis or other liver disease (transaminase levels \< 2 X the upper limit of normal will be considered acceptable), or untreated diabetes
• Previous history of CI-581 abuse, and/or a history of adverse reaction/experience wtih prior exposure to CI-581 or benzodiazepines
• BMI \> 35, or a history of unmanaged obstructive sleep apnea
• First degree relative with a psychotic disorder (bipolar disorder with psychotic features, schizophrenia, schizoaffective disorder, or psychosis NOS)
• History of opioid overdose over the past 2 years requiring medical intervention
• Currently using methadone or buprenorphine

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

GluN2C-2D antagonist UBP145; Naltrexone

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Linda Sherman
• Organization: NYSPI

lsherma@nyspi.columbia.edu

6467747158

Study Officials

• Elias Dakwar, MD

  NYSPI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical Psychiatry

Study Record Dates

• First Submitted: April 26, 2015
• First Posted: May 7, 2015
• Study Start: January 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 8, 2019
• Results First Posted: September 6, 2017

Record last verified: 2019-04

Locations

US (1)