Methadone or Buprenorphine Detoxoxification
Conditions
Brief summary
The investigators are proposing a randomized pilot feasibility study to evaluate the effects of galantamine versus placebo on preventing relapse to opioid use following tapering from methadone or buprenorphine maintenance (Medication Assisted Treatment, or MAT) among adults with opioid use disorder, with additional behavioral therapy (web-based cognitive behavioral therapy) provided across all conditions to help individuals successfully transition from MAT to a drug-free state.
Detailed description
This is a randomized pilot study to examine the potential use of galantamine as an adjunct to the standard buprenorphine or methadone taper in the context of behavioral support. Early abstinence from opioids is associated with high relapse rates and there is a great need to develop interventions that will prevent relapse to opioid use. In this randomized pilot, 30 adults enrolled in the methadone or buprenorphine maintenance programs at the APT Foundation and who have sought a medically supervised, voluntary taper from these medications will be offered participation in a double-blind, placebo controlled, randomized trial of galantamine as an adjunct to standard tapering procedures at this clinic along with the combined approach utilizing concurrent behavior therapy. Primary outcomes will be: (1) successful completion of taper (achieving a methadone/buprenorphine dose of 0), (2) opioid withdrawal symptoms, and (3) opioid use, assessed by self-report and urine samples during and up to 3 months after the end of opioid taper. The investigators will also closely monitor patient comfort and safety (assessed by opioid withdrawal symptoms, adverse events, with measures of stress, sleep and pain) as well as cognitive function (assessed by the CANTAB).
Interventions
DRUGMAT taper with galantamine
Following taper from MAT (methadone or buprenorphine) participants will be given galantamine daily with access to a CBT4CBT computer program
DRUGMAT taper with placebo
Following taper from MAT (methadone or buprenorphine) participants will be given placebo daily with access to a CBT4CBT computer program
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Are male and females, between the ages of 18 and 65 * Are enrolled in the APT methadone or buprenorphine program, have been stabilized for at least one year, and who voluntarily wish to taper off MAT. * For women of child-bearing age, have a negative serum pregnancy test at screening, agree to adequate contraception to prevent pregnancy, and agree to have monthly urine pregnancy tests at the clinic. * Are fluent in English and have a 6th grade or higher reading level. * Can commit to at least 12 weeks of treatment and are willing to be randomized to treatment
Exclusion criteria
* Are undergoing administrative (non-voluntary) tapering (e.g., example due to non-payment of program fees, program rule infractions). * Meet DSM-V psychiatric classifications for lifetime schizophrenia or bipolar disorder, or have a depressive or anxiety disorder with current use of a prescribed psychotropic medication that cannot be discontinued; * Current DSM-V diagnosis of drug or alcohol use disorder (other than opioids or tobacco); * Demonstrate significant medical conditions, including asthma or chronic obstructive lung disease, history or current gastrointestinal ulcer, hepatic or renal impairment and cardiac rhythm disturbances or any other medical conditions that the study physician deems contraindicated for galantamine treatment; * Use of other medications including a) drugs that slow heart rate (e.g., beta-blockers),which may increase the risk of bradycardia and AV block and b) NSAIDs; increased potential for developing ulcers/active or occult gastrointestinal bleeding; * Have a screening liver function test (AST or ALT) greater than 3 times normal; * Known allergy or adverse reaction to galantamine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Methadone/Buprenorphine Dose to 0 mg for Successful Completion of Taper | during 10 weeks of study and up to 3 months after the end of opioid taper | Number of participants who were able to taper to 0 mg from methadone or buprenorphine over 10 weeks of treatment. Data about current medication and dose in mg was collected at the start of treatment (week 1) was recorded on a weekly medical sheet. Data was then collected weekly from participant self-report and verified through the clinic database. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Opioid Withdrawal Scale (COWS) | Data at week 0 (baseline) and week 10 (post treatment) | opioid withdrawal score at week 0 (baseline) and at 10 weeks (post treatment). 11-item scale designed to be administered by a clinician. Rates common signs and symptoms of opiate withdrawal and can be monitored over time. The summed score for the complete scale can be used to help clinicians determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. Score of 5-12 = mild; 13-24=moderate; 25-36=moderately severe; more than 36=severe withdrawal (Scale of 0 to 40). |
| Substance Use Calendar | during 10 weeks of study | number of days of opioid use, assessed by self-report |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MAT Taper With Galantamine Following initial MAT taper, participants will be given up to 16mg daily of galantamine for up to 10 weeks of the active study
MAT taper with galantamine: Following taper from MAT (methadone or buprenorphine) participants will be given galantamine daily with access to a CBT4CBT computer program | 3 |
| MAT Taper With Placebo Following initial MAT taper, participants will be given up to 16mg daily of placebo for up to 10 weeks of the active study
MAT taper with placebo: Following taper from MAT (methadone or buprenorphine) participants will be given placebo daily with access to a CBT4CBT computer program | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Total | MAT Taper With Galantamine | MAT Taper With Placebo |
|---|---|---|---|
| Age, Continuous | 43.8 years STANDARD_DEVIATION 17.4 | 39.3 years STANDARD_DEVIATION 19.7 | 48.3 years STANDARD_DEVIATION 17.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Medication dose-Buprenorphine | 2.3 mg STANDARD_DEVIATION 1.5 | 2.5 mg STANDARD_DEVIATION 2.1 | 2.0 mg |
| Medication dose-Methadone | 15.3 mg STANDARD_DEVIATION 4.1 | 20 mg | 13.0 mg STANDARD_DEVIATION 1.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 2 Participants | 2 Participants |
| Region of Enrollment United States | 6 participants | 3 participants | 3 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 0 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
Change in Methadone/Buprenorphine Dose to 0 mg for Successful Completion of Taper
Number of participants who were able to taper to 0 mg from methadone or buprenorphine over 10 weeks of treatment. Data about current medication and dose in mg was collected at the start of treatment (week 1) was recorded on a weekly medical sheet. Data was then collected weekly from participant self-report and verified through the clinic database.
Time frame: during 10 weeks of study and up to 3 months after the end of opioid taper
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MAT Taper With Galantamine | Change in Methadone/Buprenorphine Dose to 0 mg for Successful Completion of Taper | 3 Participants |
| MAT Taper With Placebo | Change in Methadone/Buprenorphine Dose to 0 mg for Successful Completion of Taper | 2 Participants |
Secondary
Clinical Opioid Withdrawal Scale (COWS)
opioid withdrawal score at week 0 (baseline) and at 10 weeks (post treatment). 11-item scale designed to be administered by a clinician. Rates common signs and symptoms of opiate withdrawal and can be monitored over time. The summed score for the complete scale can be used to help clinicians determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. Score of 5-12 = mild; 13-24=moderate; 25-36=moderately severe; more than 36=severe withdrawal (Scale of 0 to 40).
Time frame: Data at week 0 (baseline) and week 10 (post treatment)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MAT Taper With Galantamine | Clinical Opioid Withdrawal Scale (COWS) | Week 0 (baseline) Score | 0 score on a scale | Standard Deviation 0 |
| MAT Taper With Galantamine | Clinical Opioid Withdrawal Scale (COWS) | Week 10 (Post Treatment Score) | 4.3 score on a scale | Standard Deviation 5.1 |
| MAT Taper With Placebo | Clinical Opioid Withdrawal Scale (COWS) | Week 0 (baseline) Score | .33 score on a scale | Standard Deviation 0.58 |
| MAT Taper With Placebo | Clinical Opioid Withdrawal Scale (COWS) | Week 10 (Post Treatment Score) | 4.2 score on a scale | Standard Deviation 4.1 |
Secondary
Substance Use Calendar
number of days of opioid use, assessed by self-report
Time frame: during 10 weeks of study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MAT Taper With Galantamine | Substance Use Calendar | 1.0 Days | Standard Deviation 1.73 |
| MAT Taper With Placebo | Substance Use Calendar | 0 Days | Standard Deviation 0 |