Glutamatergic Modulation to Facilitate Naltrexone Initiation in Opioid Dependence

Phase 2

Completed

• Conditions: Opioid Dependence
• Interventions: Drug: CI-581aa; Drug: Naltrexone titration and XR-NTX initiation

• Registration Number: NCT02437344
• Lead Sponsor: New York State Psychiatric Institute

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-04-26
• Study First Submitted QC: 2015-05-04
• Study First Posted: 2015-05-07
• Primary Completion: 2016-12
• Study Completion: 2016-12
• Results First Submitted: 2017-08-07
• Results First Submitted QC: 2017-08-07
• Results First Posted: 2017-09-06
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-03
• Last Update Posted: 2019-04-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CI-581aa	CI-581aa	CI-581aa will be administered 24 hours after last opioid use, and followed by naltrexone dosing
CI-581aa	Naltrexone titration and XR-NTX initiation	CI-581aa will be administered 24 hours after last opioid use, and followed by naltrexone dosing

Primary Outcome Measures

Name	Time	Method
Successful Naltrexone Initiation	2 weeks	The proportion of participants enrolled in the trial and receiving the infusion to receive XR-NTX

Secondary Outcome Measures

Name	Time	Method
Withdrawal: Subjective Opioid Withdrawal Scale (SOWS) Scores at Baseline and Administered Subsequently	4 days	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.

Trial Locations

Locations (1)

New York State Psychiatric Institute; 🇺🇸 New York, New York, United States