Galantamine and CBT4CBT Pilot to Prevent Relapse.

Pilot Study of Galantamine and CBT4CBT to Reduce Post-taper Relapse for MAT

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.

Study Overview

• Status: Completed
• Conditions: Methadone or Buprenorphine Detoxoxification
• Intervention / Treatment: Drug: MAT taper with galantamine; Drug: MAT taper with placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • APT Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 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	Drug: MAT taper with galantamine; Following taper from MAT (methadone or buprenorphine) participants will be given galantamine daily with access to a CBT4CBT computer program; Other Names: Razadyne ER, Razadyne
PLACEBO_COMPARATOR: 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	Drug: MAT taper with placebo; Following taper from MAT (methadone or buprenorphine) participants will be given placebo daily with access to a CBT4CBT computer program

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	during 10 weeks of study and up to 3 months after the end of opioid taper

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Data at week 0 (baseline) and week 10 (post treatment)
Substance Use Calendar	number of days of opioid use, assessed by self-report	during 10 weeks of study

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Kathleen M Carroll, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2018
• Primary Completion (ACTUAL): February 28, 2019
• Study Completion (ACTUAL): February 28, 2019

Study Registration Dates

• First Submitted: March 15, 2018
• First Submitted That Met QC Criteria: May 23, 2018
• First Posted (ACTUAL): June 6, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 19, 2022
• Last Update Submitted That Met QC Criteria: July 27, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Parasympathomimetics; Galantamine
• Other Study ID Numbers: 2000021868; 2P50DA009241-21 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No