Carvedilol: Cocaine Withdrawal and Pharmacotherapy Response

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00566969
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 106
• Location: 1
• Arms: 3
• Duration (Months): 64
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

A total of 120 male and female opioid dependent cocaine users will participate in this study. This study will be a 8-week double-blind, placebo controlled study examining the dose-dependent effects of carvedilol (up to 50 mg/day) in methadone stabilized patients. The design will have two phases: 1) a four-week "treatment " phase; and 2) a 4 week " taper and detoxification or transfer" phase. Subjects will be cocaine users who are on stable doses of methadone (60 to 140 mg/day). Carvedilol dose will be increased from 12.5mg/day to the target dose of either 25 or 50 mg/day as tolerated. At the end of the treatment-phase, subjects will undergo detoxification from methadone over a 2 to 4-week period based on an individual's needs, and they will concurrently be tapered off carvedilol.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence; Opiate Dependence	Drug: sugar pill; Drug: Carvedilol 25 mg; Drug: Carvedilol 50 mg	N/A

Detailed Description

The adrenergic neurotransmission serves multiple functions including learning, emotional processing and stress response to psychological and physical challenges (Huether, 1996; Sved et al., 2001). Adrenergic transmission also mediates drug withdrawal states and stress-induced relapse to drug use (Aston-Jones et al., 2004; Stewart, 2000). Consistent with these preclinical findings, adrenergic blockers showed promise as a treatment of cocaine dependence (Kampman et al., 2001b; Kampman et al., 2006). These preliminary findings are significant because there are no proven pharmacotherapies for cocaine addiction although an estimated 2.3 million of Americans aged 12 or older are regular cocaine users (SAMHSA, 2004). The societal cost of cocaine addiction is estimated to be $45 billion in the US, suggesting that development of even modestly effective cocaine pharmacotherapies will have great economic benefits. For example, availability of a medication decreasing cocaine use by 10 percent is estimated to have $745 million economic benefit in the US alone (Cartwright, 2000). Thus, developing effective treatments for cocaine addiction is an essential goal with significant benefits both for the society and the individual.

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Health Services Research
• Official Title: Cocaine Withdrawal and Pharmacotherapy Response
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Sugar Pill To be compared to active drug	Drug: sugar pill; Subjects randomized to placebo, carvedilol 25mg or 50mg; Other Names: placebo
Active Comparator: Carvedilol 25 mg To be compared to placebo and Carvedilol 50 mg	Drug: Carvedilol 25 mg; subjects randomized to placebo, carvedilol 25mg or 50mg; Other Names: Coreg
Active Comparator: Carvedilol 50 mg To be compared to placebo and Carvedilol 25 mg	Drug: Carvedilol 50 mg; subjects randomized to placebo, carvedilol 25mg or 50mg; Other Names: Coreg

Outcome Measures

Primary Outcome Measures

1. Percent Days Abstinent From Cocaine - Self Report [11 weeks]

   Percent Self reported days of abstinence from any cocaine use during the 11 week trial.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Current opioid dependence as evidenced by documented prior treatment for opioid dependence or signs of opiate withdrawals, self-reported history of opioid dependence for a consecutive 12 month period and a positive urine for opiates.

• Current cocaine use with self-reported use of cocaine > 1 time/week in at least on month preceding study entry, provision of a cocaine-positive urine and fulfilled DSM-IV criteria for cocaine dependence

• For women of childbearing age, a negative pregnancy test at screening with agreement to use adequate contraception to prevent pregnancy and monthly pregnancy tests.

Exclusion Criteria:

• current diagnosis of other drug or alcohol dependence (other than opiates, cocaine or tobacco);

• serious medical illness including asthma, diabetes, bradycardia, or other arrhythmias and major cardiovascular, renal, endocrine, hepatic disorders;

• current serious psychiatric illness or history of psychosis, schizophrenia, bipolar type I disorder or significant current suicidal or homicidal thoughts;

• screening liver function tests (AST or ALT) greater than 3 times normal;

• known allergy or intolerance for carvedilol or methadone.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Hospital	West Haven	Connecticut	United States	06516

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Mehmet Sofuoglu, M.D., Ph.D., Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00566969
• Other Study ID Numbers: 0704002562; R01DA014537; DPMC
• First Posted: Dec 4, 2007
• Last Update Posted: Apr 2, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Yale University: cocaine, opiate, methadone, carvedilol
• Additional relevant MeSH terms: Cocaine-Related Disorders; Opioid-Related Disorders; Carvedilol

Study Results

Participant Flow

Arm/Group Title	Sugar Pill	Carvedilol 25 mg	Carvedilol 50 mg
Arm/Group Description	To be compared to active drug sugar pill: randomly given 25mg or 50mg of a sugar pill or the active comparator	To be compared to sugar pill carvedilol: randomly assigned to 25mg or 50mg of Carvedilol or sugar pill, dose determined by height and weight.	To be compared to sugar pill carvedilol: randomly assigned to 25mg or 50mg of Carvedilol or sugar pill, dose determined by height and weight.
Period Title: Overall Study
STARTED	34	37	35
COMPLETED	19	28	23
NOT COMPLETED	15	9	12

Baseline Characteristics

Arm/Group Title	Sugar Pill	Carvedilol 25 mg	Carvedilol 50 mg	Total
Arm/Group Description	To be compared to active drug sugar pill: Subjects randomized to placebo, carvedilol 25mg or 50mg	To be compared to placebo and Carvedilol 50 mg carvedilol: subjects randomized to placebo, carvedilol 25mg or 50mg	To be compared to placebo and Carvedilol 25 mg Carvedilol: subjects randomized to placebo, carvedilol 25mg or 50mg	Total of all reporting groups
Overall Participants	34	37	35	106
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.6 (9.1)	37.7 (10.9)	39.1 (10.9)	38.1 (10.3)
Sex: Female, Male (Count of Participants)
Female	15 44.1%	14 37.8%	11 31.4%	40 37.7%
Male	19 55.9%	23 62.2%	24 68.6%	66 62.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	12 35.3%	10 27%	4 11.4%	26 24.5%
White	21 61.8%	24 64.9%	25 71.4%	70 66%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2.9%	3 8.1%	6 17.1%	10 9.4%

Outcome Measures

1. Primary Outcome

Title	Percent Days Abstinent From Cocaine - Self Report
Description	Percent Self reported days of abstinence from any cocaine use during the 11 week trial.
Time Frame	11 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sugar Pill	Carvedilol 25 mg	Carvedilol 50 mg
Arm/Group Description	To be compared to active drug sugar pill: randomly given 25mg or 50mg of a sugar pill or the active comparator	To be compared to sugar pill carvedilol: randomly assigned to 25mg or 50mg of Carvedilol or sugar pill, dose determined by height and weight.	To be compared to sugar pill carvedilol: randomly assigned to 25mg or 50mg of Carvedilol or sugar pill, dose determined by height and weight.
Measure Participants	19	28	23
Mean (Standard Deviation) [percentage of days]	72.9 (25.3)	72.9 (29)	59.3 (31.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sugar Pill, Carvedilol 25 mg, Carvedilol 50 mg
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	A hierarchical linear model was used to account for unequal variance and covariance structures across time.
Statistical Test of Hypothesis	p-Value	.10
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	5 years
Arm/Group Title	Sugar Pill		Carvedilol 25 mg		Carvedilol 50 mg
Arm/Group Description	To be compared to active drug sugar pill: randomly given 25mg or 50mg of a sugar pill or the active comparator		To be compared to sugar pill carvedilol: randomly assigned to 25mg or 50mg of Carvedilol or sugar pill, dose determined by height and weight.		To be compared to sugar pill carvedilol: randomly assigned to 25mg or 50mg of Carvedilol or sugar pill, dose determined by height and weight.
All Cause Mortality
	Sugar Pill		Carvedilol 25 mg		Carvedilol 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Sugar Pill		Carvedilol 25 mg		Carvedilol 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/28 (0%)		0/23 (0%)
Other (Not Including Serious) Adverse Events
	Sugar Pill		Carvedilol 25 mg		Carvedilol 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/19 (73.7%)		13/28 (46.4%)		13/23 (56.5%)
Gastrointestinal disorders
Constipation	13/19 (68.4%)	13	11/28 (39.3%)	11	13/23 (56.5%)	13
Decreased appetitie	6/19 (31.6%)	6	7/28 (25%)	7	4/23 (17.4%)	4
Nervous system disorders
Numbness	3/19 (15.8%)	3	7/28 (25%)	7	7/23 (30.4%)	7
Cramps	4/19 (21.1%)	4	4/28 (14.3%)	4	4/23 (17.4%)	4
Headache	7/19 (36.8%)	7	9/28 (32.1%)	9	8/23 (34.8%)	8
Psychiatric disorders
Disturbed concentration	6/19 (31.6%)	6	5/28 (17.9%)	5	7/23 (30.4%)	7
Agitation	11/19 (57.9%)	11	13/28 (46.4%)	13	7/23 (30.4%)	7
Tiredness	13/19 (68.4%)	13	13/28 (46.4%)	13	11/23 (47.8%)	11
Drowsiness	6/19 (31.6%)	6	10/28 (35.7%)	10	7/23 (30.4%)	7
Insomnia	14/19 (73.7%)	14	13/28 (46.4%)	13	11/23 (47.8%)	11
Nightmares	5/19 (26.3%)	5	5/28 (17.9%)	5	7/23 (30.4%)	7
Depression	10/19 (52.6%)	10	11/28 (39.3%)	11	11/23 (47.8%)	11
Anxiety	8/19 (42.1%)	8	10/28 (35.7%)	10	11/23 (47.8%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.