Glutamatergic Modulation to Facilitate Naltrexone Initiation in Opioid Dependence

Study Overview
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Brief Summary
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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).

Official Title
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Glutamatergic Modulation to Facilitate Naltrexone Initiation in Opioid Dependence

Conditions
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Opioid Dependence

Intervention / Treatment
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* Drug: CI-581aa
* Drug: Naltrexone titration and XR-NTX initiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 21-60 years of age Capacity to consent and comply with study procedures Seeking treatment Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |