Galantamine and CBT4CBT Pilot to Prevent Relapse.

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).

• MAT taper with galantamine (Drug), also known as Razadyne ER, Razadyne: Following taper from MAT (methadone or buprenorphine) participants will be given galantamine daily with access to a CBT4CBT computer program
• MAT taper with placebo (Drug): Following taper from MAT (methadone or buprenorphine) participants will be given placebo daily with access to a CBT4CBT computer program

Primary outcomes

• 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 outcomes

• 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

Sex: All, ages: 18 Years to 65 Years

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

Participant flow

Outcome results

• Change in Methadone/Buprenorphine Dose to 0 mg for Successful Completion of Taper (Primary), Count of participants, Participants: MAT Taper With Galantamine 3; MAT Taper With Placebo 2
• Clinical Opioid Withdrawal Scale (COWS) (Secondary), Mean, score on a scale: MAT Taper With Galantamine 0 +/- 0; MAT Taper With Placebo .33 +/- .58
• Substance Use Calendar (Secondary), Mean, Days: MAT Taper With Galantamine 1.0 +/- 1.73; MAT Taper With Placebo 0 +/- 0

Adverse events

Time frame: 10 weeks of taper

• Study Protocol and Statistical Analysis Plan (PDF, 2018-10-10)
• Informed Consent Form (PDF, 2018-10-10)

• Kathleen M Carroll, PhD, Principal investigator, Yale University

NIH grants: P50DA009241