Galantamine and CBT4CBT Pilot to Prevent Relapse.

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03547622
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 6
• Location: 1
• Arms: 2
• Actual Duration (Months): 10
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Methadone or Buprenorphine Detoxoxification	Drug: MAT taper with galantamine; Drug: MAT taper with placebo	Early Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Pilot Study of Galantamine and CBT4CBT to Reduce Post-taper Relapse for MAT
• Actual Study Start Date: May 1, 2018
• Actual Primary Completion Date: Feb 28, 2019
• Actual Study Completion Date: Feb 28, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

2. Substance Use Calendar [during 10 weeks of study]

   number of days of opioid use, assessed by self-report

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	APT Foundation	New Haven	Connecticut	United States	06511

Sponsors and Collaborators

• Yale University
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Kathleen M Carroll, PhD, Yale University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 10, 2018
• Informed Consent Form - Oct 10, 2018

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT03547622
• Other Study ID Numbers: 2000021868; 2P50DA009241-21
• First Posted: Jun 6, 2018
• Last Update Posted: Aug 19, 2022
• Last Verified: Jul 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Recurrence; Galantamine

Study Results

Participant Flow

Arm/Group Title	MAT Taper With Galantamine	MAT Taper With Placebo
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	3	3
COMPLETED	3	2
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	MAT Taper With Galantamine	MAT Taper With Placebo	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	3	3	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.3 (19.7)	48.3 (17.6)	43.8 (17.4)
Sex: Female, Male (Count of Participants)
Female	3 100%	2 66.7%	5 83.3%
Male	0 0%	1 33.3%	1 16.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 33.3%	0 0%	1 16.7%
Not Hispanic or Latino	2 66.7%	3 100%	5 83.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 33.3%	1 33.3%	2 33.3%
White	2 66.7%	2 66.7%	4 66.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	6 100%
Medication dose-Methadone (mg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg]	20	13.0 (1.4)	15.3 (4.1)
Medication dose-Buprenorphine (mg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg]	2.5 (2.1)	2.0	2.3 (1.5)

Outcome Measures

1. Primary Outcome

Title	Change in Methadone/Buprenorphine Dose to 0 mg for Successful Completion of Taper
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MAT Taper With Galantamine	MAT Taper With Placebo
Arm/Group Description	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	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
Measure Participants	3	3
Count of Participants [Participants]	3 100%	2 66.7%

2. Secondary Outcome

Title	Clinical Opioid Withdrawal Scale (COWS)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MAT Taper With Galantamine	MAT Taper With Placebo
Arm/Group Description	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	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
Measure Participants	3	3
Week 0 (baseline) Score	0 (0)	.33 (.58)
Week 10 (Post Treatment Score)	4.3 (5.1)	4.2 (4.1)

3. Secondary Outcome

Title	Substance Use Calendar
Description	number of days of opioid use, assessed by self-report
Time Frame	during 10 weeks of study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MAT Taper With Galantamine	MAT Taper With Placebo
Arm/Group Description	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	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
Measure Participants	3	3
Mean (Standard Deviation) [Days]	1.0 (1.73)	0 (0)

Adverse Events

Time Frame	10 weeks of taper
Arm/Group Title	MAT Taper With Galantamine		MAT Taper With Placebo
Arm/Group Description	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		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
All Cause Mortality
	MAT Taper With Galantamine		MAT Taper With Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)
Serious Adverse Events
	MAT Taper With Galantamine		MAT Taper With Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	MAT Taper With Galantamine		MAT Taper With Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.