BRAC: Study of Buspirone for Relapse-Prevention in Adults With Cocaine Dependence

• Sponsor: University of Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT01641159
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 62
• Locations: 6
• Arms: 2
• Duration (Months): 10
• Patients Per Site: 10.3
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate whether or not buspirone is effective in preventing relapse in cocaine-dependent adults in inpatient/residential treatment who are planning to enter outpatient treatment upon inpatient/residential discharge.

Condition or Disease	Intervention/Treatment	Phase
Cocaine Dependence	Drug: Buspirone; Drug: Placebo	Phase 2

Detailed Description

The primary objective is to evaluate the efficacy of buspirone, relative to placebo, in preventing relapse in cocaine-dependent adults in inpatient/residential treatment who are planning to enter outpatient treatment upon inpatient/residential discharge. Secondary objectives include evaluating the impact of buspirone, relative to placebo, on other drug-abuse outcomes and on factors that may mediate buspirone's efficacy as a relapse-prevention treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Evaluation of Buspirone for Relapse-Prevention in Adults With Cocaine Dependence (BRAC)
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Buspirone plus TAU Buspirone titrated to 60 mg/day for the 15-week active study	Drug: Buspirone; Study participants will be randomly assigned to receive either buspirone or matching placebo. Following dose escalation, the target at study day 10 is to achieve the highest tolerated dose not exceeding 60 mg. Participants who are unable to reach the 60 mg dose or who need to be reduced from 60 mg due to tolerability will be maintained on 15 mg, 30 mg, or 45 mg, whichever is the highest dose tolerated.; Other Names: Buspirone hydrochloride, Buspar
Placebo Comparator: Placebo plus TAU Placebo taken daily for the 15-week active study	Drug: Placebo; Study participants will be randomly assigned to receive either buspirone or matching placebo. Placebo tablets will be identical in color and size to the buspirone tablets.; Other Names: Matched placebo

Outcome Measures

Primary Outcome Measures

1. Maximum Days of Continuous Cocaine Abstinence [study week 16]

   The primary outcome measure selected for the present two-stage protocol is the maximum days of continuous cocaine abstinence during study weeks 4-15. The Timeline Follow-back (TLFB) procedure (Sobell and Sobell, 1992; Fals-Stewart, 2000) will be used to assess the participants' self-reported use of substances for each day of the study. A rapid UDS system that screens for drugs of abuse will be used to analyze the urine samples.

Secondary Outcome Measures

1. Cocaine-use Days [study week 16]

   Cocaine use days during days 22-105 as assessed by UDS and self-report combined with no imputation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. be 18 years of age or older

2. be able to understand the study, and having understood, provide written informed consent in English

3. meet DSM-IV-TR diagnostic criteria for current (within the last 12 months) dependence for cocaine, must self-report having used crack cocaine a minimum of four times in the 28 days prior to inpatient/residential admission, and must report that their typical pattern of use is at least once a week

4. have a willingness to comply with all study procedures and medication instructions

5. be enrolled in an inpatient/residential program at a participating CTP, scheduled to be in inpatient/residential treatment for 12-19 days when randomized, and planning to enroll in local outpatient treatment through the end of the active treatment phase (i.e., study week 15)

6. if female and of child bearing potential, agree to use one of the following methods of birth control:

• oral contraceptives

• contraceptive patch

• barrier (diaphragm or condom)

• intrauterine contraceptive system

• levonorgestrel implant

• medroxyprogesterone acetate contraceptive injection

• complete abstinence from sexual intercourse

• hormonal vaginal contraceptive ring

Exclusion Criteria:

1. meet DSM-IV-TR diagnostic criteria for current (within the last 12 months) opioid dependence

2. have a medical or psychiatric condition that, in the judgment of the study physician, would make study participation unsafe or which would make treatment compliance difficult. Medical conditions that may compromise participant safety or study conduct include, but are not limited to:

• AIDS according to the current CDC criteria for AIDS

• liver function tests greater than 3X upper limit of normal

• serum creatinine greater than 2 mg/dL

1. have a psychiatric disorder requiring continued treatment with a psychotropic medication

2. have a known or suspected hypersensitivity to buspirone

3. be pregnant or breastfeeding

4. have used any of the following medications within 14 days of randomization: monoamine oxidase (MAO) inhibitors such as phenelzine (Nardil), selegiline (Eldepryl), isocarboxazid (Marplan), or tranylcypromine (Parnate)

5. be taking any medications which, in the judgment of the study physician, may produce interactions with buspirone that are sufficiently dangerous so as to exclude the patient from participating in the study. Alternatively, the study physician, in consultation with the patient and his or her physician, may elect to withdraw the patient from the problem medications before randomization. Some of the possible interactions are discussed in section 8.8.

6. be anyone who, in the judgment of the investigator, would not be expected to complete the study protocol (e.g., due to relocation from the clinic area, probable incarceration, etc.)

7. be a significant suicidal/homicidal risk

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gateway Community Services	Jacksonville	Florida	United States	32204
2	Maryhaven Inc	Columbus	Ohio	United States	43207
3	Penn Presbyterian	Philadelphia	Pennsylvania	United States	19104
4	Addiction Medicine Services	Pittsburgh	Pennsylvania	United States	15213
5	Morris Village/LRADAC	Columbia	South Carolina	United States	29203
6	Nexus Recovery Services	Dallas	Texas	United States	75228

Sponsors and Collaborators

• University of Cincinnati
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Theresa Winhusen, PhD, University of Cincinnati, CTN Ohio Valley Node

Study Documents (Full-Text)

None provided.

More Information

Publications

• Winhusen T, Brady KT, Stitzer M, Woody G, Lindblad R, Kropp F, Brigham G, Liu D, Sparenborg S, Sharma G, Vanveldhuisen P, Adinoff B, Somoza E. Evaluation of buspirone for relapse-prevention in adults with cocaine dependence: an efficacy trial conducted in the real world. Contemp Clin Trials. 2012 Sep;33(5):993-1002. doi: 10.1016/j.cct.2012.05.003. Epub 2012 May 19.

• Responsible Party: Theresa Winhusen, Associate Professor, Department of Psychiatry and Behavioral Neuroscience; CinARC Director, University of Cincinnati
• ClinicalTrials.gov Identifier: NCT01641159
• Other Study ID Numbers: CTN-0052; U10DA013732
• First Posted: Jul 16, 2012
• Last Update Posted: Jan 7, 2015
• Last Verified: Dec 1, 2014

• Keywords provided by Theresa Winhusen, Associate Professor, Department of Psychiatry and Behavioral Neuroscience; CinARC Director, University of Cincinnati: Cocaine; Crack; Buspirone; Relapse Prevention
• Additional relevant MeSH terms: Recurrence; Cocaine-Related Disorders; Buspirone

Study Results

Participant Flow

Arm/Group Title	Buspirone Plus TAU	Placebo Plus TAU
Arm/Group Description	Buspirone titrated to 60 mg/day for the 15-week active study Buspirone: Study participants will be randomly assigned to receive either buspirone or matching placebo. Following dose escalation, the target at study day 10 is to achieve the highest tolerated dose not exceeding 60 mg. Participants who are unable to reach the 60 mg dose or who need to be reduced from 60 mg due to tolerability will be maintained on 15 mg, 30 mg, or 45 mg, whichever is the highest dose tolerated.	Placebo taken daily for the 15-week active study Placebo: Study participants will be randomly assigned to receive either buspirone or matching placebo. Placebo tablets will be identical in color and size to the buspirone tablets.
Period Title: Overall Study
STARTED	35	27
COMPLETED	33	25
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Buspirone Plus TAU	Placebo Plus TAU	Total
Arm/Group Description	Buspirone titrated to 60 mg/day for the 15-week active study Buspirone: Study participants will be randomly assigned to receive either buspirone or matching placebo. Following dose escalation, the target at study day 10 is to achieve the highest tolerated dose not exceeding 60 mg. Participants who are unable to reach the 60 mg dose or who need to be reduced from 60 mg due to tolerability will be maintained on 15 mg, 30 mg, or 45 mg, whichever is the highest dose tolerated.	Placebo taken daily for the 15-week active study Placebo: Study participants will be randomly assigned to receive either buspirone or matching placebo. Placebo tablets will be identical in color and size to the buspirone tablets.	Total of all reporting groups
Overall Participants	35	27	62
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	35 100%	27 100%	62 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	11 31.4%	12 44.4%	23 37.1%
Male	24 68.6%	15 55.6%	39 62.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	35 100%	27 100%	62 100%
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	26 74.3%	19 70.4%	45 72.6%
White	8 22.9%	6 22.2%	14 22.6%
More than one race	1 2.9%	2 7.4%	3 4.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	35 100%	27 100%	62 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Days of Continuous Cocaine Abstinence
Description	The primary outcome measure selected for the present two-stage protocol is the maximum days of continuous cocaine abstinence during study weeks 4-15. The Timeline Follow-back (TLFB) procedure (Sobell and Sobell, 1992; Fals-Stewart, 2000) will be used to assess the participants' self-reported use of substances for each day of the study. A rapid UDS system that screens for drugs of abuse will be used to analyze the urine samples.
Time Frame	study week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Buspirone Plus TAU	Placebo Plus TAU
Arm/Group Description	Buspirone titrated to 60 mg/day for the 15-week active study Buspirone: Study participants will be randomly assigned to receive either buspirone or matching placebo. Following dose escalation, the target at study day 10 is to achieve the highest tolerated dose not exceeding 60 mg. Participants who are unable to reach the 60 mg dose or who need to be reduced from 60 mg due to tolerability will be maintained on 15 mg, 30 mg, or 45 mg, whichever is the highest dose tolerated.	Placebo taken daily for the 15-week active study Placebo: Study participants will be randomly assigned to receive either buspirone or matching placebo. Placebo tablets will be identical in color and size to the buspirone tablets.
Measure Participants	35	27
Mean (Standard Deviation) [Days]	42.9 (30.83)	46.6 (31.03)

2. Secondary Outcome

Title	Cocaine-use Days
Description	Cocaine use days during days 22-105 as assessed by UDS and self-report combined with no imputation
Time Frame	study week 16

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Buspirone Plus TAU	Placebo Plus TAU
Arm/Group Description	Buspirone titrated to 60 mg/day for the 15-week active study Buspirone: Study participants will be randomly assigned to receive either buspirone or matching placebo. Following dose escalation, the target at study day 10 is to achieve the highest tolerated dose not exceeding 60 mg. Participants who are unable to reach the 60 mg dose or who need to be reduced from 60 mg due to tolerability will be maintained on 15 mg, 30 mg, or 45 mg, whichever is the highest dose tolerated.	Placebo taken daily for the 15-week active study Placebo: Study participants will be randomly assigned to receive either buspirone or matching placebo. Placebo tablets will be identical in color and size to the buspirone tablets.
Measure Participants	35	27
Number [proportion of cocaine use days]	0.153	0.134

Adverse Events

Time Frame	Between the first dose of study drug and the last dose of study drug plus 7 days, for up to 16 weeks
Arm/Group Title	Buspirone Plus TAU		Placebo Plus TAU
Arm/Group Description	Buspirone titrated to 60 mg/day for the 15-week active study Buspirone: Study participants will be randomly assigned to receive either buspirone or matching placebo. Following dose escalation, the target at study day 10 is to achieve the highest tolerated dose not exceeding 60 mg. Participants who are unable to reach the 60 mg dose or who need to be reduced from 60 mg due to tolerability will be maintained on 15 mg, 30 mg, or 45 mg, whichever is the highest dose tolerated.		Placebo taken daily for the 15-week active study Placebo: Study participants will be randomly assigned to receive either buspirone or matching placebo. Placebo tablets will be identical in color and size to the buspirone tablets.
All Cause Mortality
	Buspirone Plus TAU		Placebo Plus TAU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Buspirone Plus TAU		Placebo Plus TAU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/35 (8.6%)		0/27 (0%)
General disorders
Chest pain	1/35 (2.9%)	1	0/27 (0%)	0
Infections and infestations
Pulmonary tuberculosis	1/35 (2.9%)	1	0/27 (0%)	0
Pneumonia	1/35 (2.9%)	1	0/27 (0%)	0
Other (Not Including Serious) Adverse Events
	Buspirone Plus TAU		Placebo Plus TAU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/35 (51.4%)		11/27 (40.7%)
Gastrointestinal disorders
Nausea	8/35 (22.9%)	11	2/27 (7.4%)	2
Vomiting	2/35 (5.7%)	3	2/27 (7.4%)	2
Dyspepsia	2/35 (5.7%)	2	1/27 (3.7%)	1
Diarrhoea	2/35 (5.7%)	2	1/27 (3.7%)	1
General disorders
Oedema peripheral	0/35 (0%)	0	2/27 (7.4%)	2
Infections and infestations
Nasopharyngitis	8/35 (22.9%)	8	4/27 (14.8%)	6
Upper respiratory tract infection	2/35 (5.7%)	2	2/27 (7.4%)	2
Bronchitis	2/35 (5.7%)	2	1/27 (3.7%)	1
Influenza	3/35 (8.6%)	3	0/27 (0%)	0
Viral infection	0/35 (0%)	0	2/27 (7.4%)	2
Investigations
Weight increased	2/35 (5.7%)	2	1/27 (3.7%)	1
Musculoskeletal and connective tissue disorders
Back pain	5/35 (14.3%)	5	2/27 (7.4%)	2
Pain in extremity	2/35 (5.7%)	2	1/27 (3.7%)	1
Arthralgia	2/35 (5.7%)	2	1/27 (3.7%)	1
Nervous system disorders
Dizziness	15/35 (42.9%)	18	1/27 (3.7%)	1
Headache	8/35 (22.9%)	8	7/27 (25.9%)	8
Somnolence	3/35 (8.6%)	3	2/27 (7.4%)	2
Psychiatric disorders
Insomnia	2/35 (5.7%)	2	0/27 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/35 (2.9%)	1	3/27 (11.1%)	3
Oropharyngeal pain	0/35 (0%)	0	3/27 (11.1%)	3
Sinus congestion	2/35 (5.7%)	2	0/27 (0%)	0
Pulmonary congestion	2/35 (5.7%)	2	0/27 (0%)	0

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.