Opioid Dependence
Conditions
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).
Interventions
DRUGCI-581aa
92 minute infusion of CI-581aa
DRUGNaltrexone titration and XR-NTX initiation
participants will be provided a titration of naltrexone that culminates in the injection of XR-NTX
Sponsors
National Institute on Drug Abuse (NIDA)
New York State Psychiatric Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful Naltrexone Initiation | 2 weeks | The proportion of participants enrolled in the trial and receiving the infusion to receive XR-NTX |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CI-581aa CI-581aa will be administered 24 hours after last opioid use, and followed by naltrexone dosing
CI-581aa: 92 minute infusion of CI-581aa
Naltrexone titration and XR-NTX initiation: participants will be provided a titration of naltrexone that culminates in the injection of XR-NTX | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | CI-581aa |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 37.8 years STANDARD_DEVIATION 12.3 |
| baseline opioid use (morphine equivalents) | 297.7 morphine eq, in mg STANDARD_DEVIATION 113.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 16 |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Successful Naltrexone Initiation
The proportion of participants enrolled in the trial and receiving the infusion to receive XR-NTX
Time frame: 2 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CI-581aa | Successful Naltrexone Initiation | 11 Participants |
Secondary
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.
Time frame: 4 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CI-581aa | Withdrawal: Subjective Opioid Withdrawal Scale (SOWS) Scores at Baseline and Administered Subsequently | 34 units on a scale | Standard Error 7 |