Glutamatergic Modulation to Facilitate Naltrexone Initiation in Opioid Dependence

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).

Study Overview

• Status: Completed
• Conditions: Opioid Dependence
• Intervention / Treatment: Drug: CI-581aa; Drug: Naltrexone titration and XR-NTX initiation

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Active opioid dependence, with at least one positive utox result; no history of opioid overdose; and not currently using methadone or buprenorphine
2. Physically healthy
3. No adverse reactions to study medications
4. 21-60 years of age
5. Capacity to consent and comply with study procedures
6. Seeking treatment

Exclusion Criteria:

1. 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.
2. Physiological dependence on another substance requiring medical management, such as alcohol or benzodiazepines, excluding caffeine, nicotine, and cannabis
3. Pregnant or interested in becoming pregnant
4. Delirium, Dementia, Amnesia, Cognitive Disorders, or dissociative disorders
5. Current suicide risk or a history of suicide attempt within the past 2 years
6. On psychotropic or other medication whose effect could be disrupted by participation in the study
7. Recent history of significant violence (past 2 years).
8. Heart disease as indicated by history, abnormal ECG, previous cardiac surgery.
9. 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
10. Previous history of CI-581 abuse, and/or a history of adverse reaction/experience wtih prior exposure to CI-581 or benzodiazepines
11. BMI > 35, or a history of unmanaged obstructive sleep apnea
12. First degree relative with a psychotic disorder (bipolar disorder with psychotic features, schizophrenia, schizoaffective disorder, or psychosis NOS)
13. History of opioid overdose over the past 2 years requiring medical intervention
14. Currently using methadone or buprenorphine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CI-581aa; CI-581aa will be administered 24 hours after last opioid use, and followed by naltrexone dosing	Drug: CI-581aa; 92 minute infusion of CI-581aa; Other Names: NMDA antagonist; Drug: Naltrexone titration and XR-NTX initiation; participants will be provided a titration of naltrexone that culminates in the injection of XR-NTX; Other Names: naltrexone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful Naltrexone Initiation	The proportion of participants enrolled in the trial and receiving the infusion to receive XR-NTX	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Withdrawal: Subjective Opioid Withdrawal Scale (SOWS) Scores at Baseline and Administered Subsequently	Subjective Opioid Withdrawal Scale (SOWS) is a scale out of 64 points assessing withdrawal severity that is administered serially, every several hours, over the course of the naltrexone initiation. The questionnaire assesses symptoms that the patient rates on a scale of 0 (not at all) to 4 (extremely). The difference in total (sum) scores between baseline and end-of-induction will be reported. Scores range from 0 to 64.	4 days

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: April 26, 2015
• First Submitted That Met QC Criteria: May 4, 2015
• First Posted (Estimate): May 7, 2015

Study Record Updates

• Last Update Posted (Actual): April 8, 2019
• Last Update Submitted That Met QC Criteria: April 3, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: #7057