Glutamatergic Modulation to Facilitate Naltrexone Initiation in Opioid Dependence
Condition: Opioid Dependence
MeSH terms: Opioid-Related Disorders
Intervention: CI-581aa; Naltrexone titration and XR-NTX initiation
Intervention description: 92 minute infusion of CI-581aa; participants will be provided a titration of naltrexone that culminates in the injection of XR-NTX
Intervention MeSH terms: Naltrexone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 21 Years
Maximum age: 60 Years
Healthy volunteers: No

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).
    

Eligibility criteria:

        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