Galantamine to Enhance Cognitive Behavioral Therapy for Cocaine Abuse

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00809835
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 120
• Locations: 2
• Arms: 4
• Duration (Months): 85
• Patients Per Site: 60
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

We are testing to see if Galantamine, a learning enhancing medication, will help methadone maintained cocaine abusers with their learning and memory specific to CBT using an innovative CBT computer program.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence	Drug: Galantamine; Behavioral: Computer Assisted Cognitive Behavioral Therapy (CBT)	Phase 2

Detailed Description

We are proposing a randomized double blind clinical trial of galantamine and our innovative computer-assisted version of CBT, alone and in combination, to improve treatment outcome and cognitive functioning among cocaine users. The proposed study will be the first to evaluate a cognitive enhancing medication as a means of enhancing the effects of an extremely promising empirically validated behavioral therapy for addiction, and hence bridge cognitive neuroscience and behavioral therapies development.

The aim is to conduct a 12 week randomized placebo controlled trial, using a 2x2 factorial model, that will evaluate the efficacy of adding computer assisted training in CBT ("CBT4CBT") and galantamine to standard treatment for 160 cocaine abusing or dependent methadone-maintained individuals. Participants will be randomized to (1) standard treatment (TAU) plus placebo, (2) TAU plus galantamine, (3) TAU plus CBT4CBT plus placebo, or (4) TAU plus CBT4CBT plus galantamine.

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Galantamine to Enhance Cognitive Behavioral Therapy for Cocaine Abuse With Methadone Maintained Individuals
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Standard Treatment As Usual (TAU) Standard Treatment plus placebo for cocaine abusing or dependent methadone-maintained individuals. This consists of daily methadone visits plus one individual and one group session per week, and patients may participate in additional treatments such as HIV education and treatment. The counseling program's theoretical orientation is described as client-centered.
Experimental: TAU Plus Galantamine Standard treatment plus Galantamine. In this study, we will use 8 mg galantamine extended release (ER). Galantamine ER is used once daily. The recommended initial dose is 8 mg/day and the maintenance dose is 16-24 mg/day.	Drug: Galantamine; Daily 8 mg galantamine capsule; Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine
Experimental: TAU plus Computer Assisted Cognitive Behavioral Therapy (CBT) TAU plus computer assisted CBT plus placebo. All participants assigned to this condition will also be offered up to 60 minutes per week to work with the CBT for CBT program, onsite at the clinic, in a private space and using a computer provided by the research project. Patients will have the choice of how they choose to use the computer, that is, in two 30-minute sessions or one one-hour session.	Behavioral: Computer Assisted Cognitive Behavioral Therapy (CBT); CBT a psychotherapeutic approach that addresses dysfunctional emotions, maladaptive behaviors and cognitive processes and contents through a number of goal-oriented, explicit systematic procedures. The name refers to behavior therapy, cognitive therapy, and to therapy based upon a combination of basic behavioral and cognitive principles and research.
Experimental: TAU plus CBT plus galantamine Standard treatment, plus computer assisted cognitive behavioral therapy, plus galantamine.	Drug: Galantamine; Daily 8 mg galantamine capsule; Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine ; Behavioral: Computer Assisted Cognitive Behavioral Therapy (CBT); CBT a psychotherapeutic approach that addresses dysfunctional emotions, maladaptive behaviors and cognitive processes and contents through a number of goal-oriented, explicit systematic procedures. The name refers to behavior therapy, cognitive therapy, and to therapy based upon a combination of basic behavioral and cognitive principles and research.

Outcome Measures

Primary Outcome Measures

1. Cocaine Use [12 weeks]

   Reduction in cocaine use, operationalized as the frequency of cocaine use by month using timeline followback.

2. Cocaine Abstinence [12 weeks]

   operationalized by percentage of drug-free urine specimens submitted (We will use the Branan ToxCup Drug Screen Cup onsite TESTCUP system for detection of cocaine, methamphetamine, THC, benzodiazepine, and opioids) at 12 Weeks

Secondary Outcome Measures

1. Cognitive Function [12 weeks]

   A composite using a carefully selected neuropsychological battery that includes measures of executive cognitive functioning frequently affected among cocaine users, likely to be important moderators of CBT4CBT, and sensitive to galantamine effects. These will include measures of multiple aspects of attention, cognitive inhibition, sustained attention (CANTAB), decision making (BART), and memory (digit span). Scores ranged from -1.77 to 1.42 with a higher score indicating higher cognitive functioning.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and females between ages of 18 and 50

• Enrolled in RNP methadone program and stable on methadone for at least 3 weeks

• Current cocaine abuse or dependence according to DSM-IV criteria

• No current medical problems and normal ECG

• If female, not currently pregnant or breast feeding and using reliable birth control

• Fluent in English and have at least a 6th grade reading level

• Can commit to 12 weeks of treatment and are willing to be randomized

Exclusion Criteria:

• Current major psychiatric illness including mood, psychotic or anxiety disorder

• History of major medical illnesses including asthma, chronic obstructive lung disease, gastrointestinal ulcer, hepatic or renal impairment, cardiac rhythm disturbances

• Use of medications including beta blockers and NASAIDs

• Known allergy to Galantamine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kinsella Treatment Center (KTC)	Bridgeport	Connecticut	United States	06604
2	Regional Network of Programs	Stratford	Connecticut	United States	06615

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Kathleen M Carroll, Ph.D., Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00809835
• Other Study ID Numbers: 0708002943; R01DA015969-13
• First Posted: Dec 17, 2008
• Last Update Posted: Jan 30, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Yale University: Cocaine; Methadone; CBT
• Additional relevant MeSH terms: Cocaine-Related Disorders; Galantamine

Study Results

Participant Flow

Arm/Group Title	Galantamine and CBT	Galantamine Only	Placebo and CBT	Placebo Only
Arm/Group Description	Drug: Galantamine Daily 8 mg galantamine capsule Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine Behavioral: Computer Assisted Cognitive Behavioral Therapy (CBT) CBT a psychotherapeutic approach that addresses dysfunctional emotions, maladaptive behaviors and cognitive processes and contents through a number of goal-oriented, explicit systematic procedures. The name refers to behavior therapy, cognitive therapy, and to therapy based upon a combination of basic behavioral and cognitive principles and research.	Drug: Galantamine Daily 8 mg galantamine capsule Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine	TAU plus computer assisted CBT plus placebo. All participants assigned to this condition will also be offered up to 60 minutes per week to work with the CBT for CBT program, onsite at the clinic, in a private space and using a computer provided by the research project. Patients will have the choice of how they choose to use the computer, that is, in two 30-minute sessions or one one-hour session.	Standard Treatment plus placebo for cocaine abusing or dependent methadone-maintained individuals. This consists of daily methadone visits plus one individual and one group session per week, and patients may participate in additional treatments such as HIV education and treatment. The counseling program's theoretical orientation is described as client-centered.
Period Title: Overall Study
STARTED	28	27	38	27
COMPLETED	20	20	27	25
NOT COMPLETED	8	7	11	2

Baseline Characteristics

Arm/Group Title	Galantamine and CBT	Galantamine	Placebo and CBT	Placebo Only	Total
Arm/Group Description	Drug: Galantamine Daily 8 mg galantamine capsule Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine Behavioral: Computer Assisted Cognitive Behavioral Therapy (CBT) CBT a psychotherapeutic approach that addresses dysfunctional emotions, maladaptive behaviors and cognitive processes and contents through a number of goal-oriented, explicit systematic procedures. The name refers to behavior therapy, cognitive therapy, and to therapy based upon a combination of basic behavioral and cognitive principles and research.	Drug: Galantamine Daily 8 mg galantamine capsule Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine	Computer assisted CBT plus placebo. All participants assigned to this condition will also be offered up to 60 minutes per week to work with the CBT for CBT program, onsite at the clinic, in a private space and using a computer provided by the research project. Patients will have the choice of how they choose to use the computer, that is, in two 30-minute sessions or one one-hour session.	Standard Treatment plus placebo for cocaine abusing or dependent methadone-maintained individuals. This consists of daily methadone visits plus one individual and one group session per week, and patients may participate in additional treatments such as HIV education and treatment. The counseling program's theoretical orientation is described as client-centered.	Total of all reporting groups
Overall Participants	28	27	38	27	120
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.04 (8.72)	38.70 (10.79)	39.82 (8.99)	36.30 (9.41)	38.36 (9.43)
Sex: Female, Male (Count of Participants)
Female	12 42.9%	15 55.6%	19 50%	16 59.3%	62 51.7%
Male	16 57.1%	12 44.4%	19 50%	11 40.7%	58 48.3%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	12 42.9%	15 55.6%	19 50%	16 59.3%	62 51.7%
African-American	7 25%	6 22.2%	9 23.7%	3 11.1%	25 20.8%
Hispanic	9 32.1%	6 22.2%	9 23.7%	8 29.6%	32 26.7%
Multiracial/Other	0 0%	0 0%	1 2.6%	0 0%	1 0.8%

Outcome Measures

1. Primary Outcome

Title	Cocaine Use
Description	Reduction in cocaine use, operationalized as the frequency of cocaine use by month using timeline followback.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Presented are data for those measured at baseline and at 12 weeks. 2 individuals in the Galantamine arm were not measured at 12 weeks.

Arm/Group Title	Galantamine and CBT	Galantamine	Placebo and CBT	Placebo Only
Arm/Group Description	Drug: Galantamine Daily 8 mg galantamine capsule Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine Behavioral: Computer Assisted Cognitive Behavioral Therapy (CBT) CBT a psychotherapeutic approach that addresses dysfunctional emotions, maladaptive behaviors and cognitive processes and contents through a number of goal-oriented, explicit systematic procedures. The name refers to behavior therapy, cognitive therapy, and to therapy based upon a combination of basic behavioral and cognitive principles and research.	Drug: Galantamine Daily 8 mg galantamine capsule Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine	Computer assisted CBT plus placebo. All participants assigned to this condition will also be offered up to 60 minutes per week to work with the CBT for CBT program, onsite at the clinic, in a private space and using a computer provided by the research project. Patients will have the choice of how they choose to use the computer, that is, in two 30-minute sessions or one one-hour session.	Standard Treatment plus placebo for cocaine abusing or dependent methadone-maintained individuals. This consists of daily methadone visits plus one individual and one group session per week, and patients may participate in additional treatments such as HIV education and treatment. The counseling program's theoretical orientation is described as client-centered.
Measure Participants	28	27	38	27
Baseline	18.82 (8.68)	14.81 (9.05)	15.68 (7.78)	14.85 (8.47)
12 Weeks	8.60 (6.95)	6.32 (6.52)	7.65 (7.41)	10.25 (7.79)

2. Primary Outcome

Title	Cocaine Abstinence
Description	operationalized by percentage of drug-free urine specimens submitted (We will use the Branan ToxCup Drug Screen Cup onsite TESTCUP system for detection of cocaine, methamphetamine, THC, benzodiazepine, and opioids) at 12 Weeks
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Three arm had one subject drop out before study medication was given- therefore the number analyzed are those that received first treatment.

Arm/Group Title	Galantamine and CBT	Galantamine	Placebo and CBT	Placebo Only
Arm/Group Description	Drug: Galantamine Daily 8 mg galantamine capsule Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine Behavioral: Computer Assisted Cognitive Behavioral Therapy (CBT) CBT a psychotherapeutic approach that addresses dysfunctional emotions, maladaptive behaviors and cognitive processes and contents through a number of goal-oriented, explicit systematic procedures. The name refers to behavior therapy, cognitive therapy, and to therapy based upon a combination of basic behavioral and cognitive principles and research.	Drug: Galantamine Daily 8 mg galantamine capsule Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine	Computer assisted CBT plus placebo. All participants assigned to this condition will also be offered up to 60 minutes per week to work with the CBT for CBT program, onsite at the clinic, in a private space and using a computer provided by the research project. Patients will have the choice of how they choose to use the computer, that is, in two 30-minute sessions or one one-hour session.	Standard Treatment plus placebo for cocaine abusing or dependent methadone-maintained individuals. This consists of daily methadone visits plus one individual and one group session per week, and patients may participate in additional treatments such as HIV education and treatment. The counseling program's theoretical orientation is described as client-centered.
Measure Participants	27	26	37	27
Mean (Standard Deviation) [percentage of negative urines]	22.45 (35.62)	31.13 (34.16)	20.49 (27.60)	14.78 (19.11)

3. Secondary Outcome

Title	Cognitive Function
Description	A composite using a carefully selected neuropsychological battery that includes measures of executive cognitive functioning frequently affected among cocaine users, likely to be important moderators of CBT4CBT, and sensitive to galantamine effects. These will include measures of multiple aspects of attention, cognitive inhibition, sustained attention (CANTAB), decision making (BART), and memory (digit span). Scores ranged from -1.77 to 1.42 with a higher score indicating higher cognitive functioning.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All participants did not complete the CANTAB assessments at both pre and post treatment. Reasons for not completing were refusal to complete the tasks, inability to complete the tasks in a manner in which they could be scored and equipment or computer problems.

Arm/Group Title	Galantamine and CBT	Galantamine	Placebo and CBT	Placebo Only
Arm/Group Description	Drug: Galantamine Daily 8 mg galantamine capsule Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine Behavioral: Computer Assisted Cognitive Behavioral Therapy (CBT) CBT a psychotherapeutic approach that addresses dysfunctional emotions, maladaptive behaviors and cognitive processes and contents through a number of goal-oriented, explicit systematic procedures. The name refers to behavior therapy, cognitive therapy, and to therapy based upon a combination of basic behavioral and cognitive principles and research.	Drug: Galantamine Daily 8 mg galantamine capsule Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine	Computer assisted CBT plus placebo. All participants assigned to this condition will also be offered up to 60 minutes per week to work with the CBT for CBT program, onsite at the clinic, in a private space and using a computer provided by the research project. Patients will have the choice of how they choose to use the computer, that is, in two 30-minute sessions or one one-hour session.	Standard Treatment plus placebo for cocaine abusing or dependent methadone-maintained individuals. This consists of daily methadone visits plus one individual and one group session per week, and patients may participate in additional treatments such as HIV education and treatment. The counseling program's theoretical orientation is described as client-centered.
Measure Participants	18	22	25	19
Mean (Standard Deviation) [scores on a scale]	-.12 (.58)	.11 (.50)	-.06 (.71)	.03 (.49)

Adverse Events

Arm/Group Title	Galantamine and CBT		Galantamine		Placebo and CBT		Placebo Only
Arm/Group Description	Drug: Galantamine Daily 8 mg galantamine capsule Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine Behavioral: Computer Assisted Cognitive Behavioral Therapy (CBT) CBT a psychotherapeutic approach that addresses dysfunctional emotions, maladaptive behaviors and cognitive processes and contents through a number of goal-oriented, explicit systematic procedures. The name refers to behavior therapy, cognitive therapy, and to therapy based upon a combination of basic behavioral and cognitive principles and research.		Drug: Galantamine Daily 8 mg galantamine capsule Other Names: Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine		Computer assisted CBT plus placebo. All participants assigned to this condition will also be offered up to 60 minutes per week to work with the CBT for CBT program, onsite at the clinic, in a private space and using a computer provided by the research project. Patients will have the choice of how they choose to use the computer, that is, in two 30-minute sessions or one one-hour session.		Standard Treatment plus placebo for cocaine abusing or dependent methadone-maintained individuals. This consists of daily methadone visits plus one individual and one group session per week, and patients may participate in additional treatments such as HIV education and treatment. The counseling program's theoretical orientation is described as client-centered.
All Cause Mortality
	Galantamine and CBT		Galantamine		Placebo and CBT		Placebo Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Galantamine and CBT		Galantamine		Placebo and CBT		Placebo Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/28 (14.3%)		6/27 (22.2%)		6/38 (15.8%)		5/27 (18.5%)
Gastrointestinal disorders
Medical hospitalization	0/28 (0%)	0	1/27 (3.7%)	1	0/38 (0%)	0	0/27 (0%)	0
General disorders
Medical Hospitalization	0/28 (0%)	0	1/27 (3.7%)	1	2/38 (5.3%)	2	0/27 (0%)	0
Psychiatric disorders
Inpatient Substance Use Treatment Hospitalization	3/28 (10.7%)	5	2/27 (7.4%)	2	3/38 (7.9%)	5	5/27 (18.5%)	5
Inpatient Psychiatric Hospitalization	1/28 (3.6%)	1	2/27 (7.4%)	2	0/38 (0%)	0	0/27 (0%)	0
Surgical and medical procedures
Medical hospitalization	0/28 (0%)	0	0/27 (0%)	0	1/38 (2.6%)	1	0/27 (0%)	0
Other (Not Including Serious) Adverse Events
	Galantamine and CBT		Galantamine		Placebo and CBT		Placebo Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/28 (53.6%)		10/27 (37%)		16/38 (42.1%)		14/27 (51.9%)
Gastrointestinal disorders
Nausea	11/28 (39.3%)	17	2/27 (7.4%)	2	5/38 (13.2%)	14	6/27 (22.2%)	6
indigestion	2/28 (7.1%)	3	0/27 (0%)	0	3/38 (7.9%)	4	2/27 (7.4%)	2
Diarrhea or Constipation	4/28 (14.3%)	7	0/27 (0%)	0	8/38 (21.1%)	13	3/27 (11.1%)	3
General disorders
Fatigue	2/28 (7.1%)	3	3/27 (11.1%)	5	8/38 (21.1%)	13	4/27 (14.8%)	7
agitation	4/28 (14.3%)	5	0/27 (0%)	0	3/38 (7.9%)	3	1/27 (3.7%)	1
headache	5/28 (17.9%)	6	6/27 (22.2%)	8	6/38 (15.8%)	9	3/27 (11.1%)	5
Tremors	1/28 (3.6%)	1	0/27 (0%)	0	1/38 (2.6%)	1	0/27 (0%)	0
Dizziness	3/28 (10.7%)	5	2/27 (7.4%)	3	2/38 (5.3%)	3	1/27 (3.7%)	1
Blood in Stool	0/28 (0%)	0	0/27 (0%)	0	1/38 (2.6%)	1	0/27 (0%)	0
Abdominal Pain	4/28 (14.3%)	5	1/27 (3.7%)	1	4/38 (10.5%)	5	1/27 (3.7%)	1
Loss of Appetite	7/28 (25%)	10	2/27 (7.4%)	3	6/38 (15.8%)	8	3/27 (11.1%)	3
Weight Loss	0/28 (0%)	0	0/27 (0%)	0	3/38 (7.9%)	3	1/27 (3.7%)	1
Skin and subcutaneous tissue disorders
Rash	0/28 (0%)	0	0/27 (0%)	0	1/38 (2.6%)	1	0/27 (0%)	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.