Counseling for Primary Care Office-based Buprenorphine

• Sponsor: Yale University
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): David Fiellin, Yale University

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Opiate Dependence
Interventions	Behavioral: Manual-guided Physician Management (PM); Behavioral: Physician Management (PM) combined with on-site manual-guided Cognitive Behavioral Therapy (CBT)
Enrollment	141

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Physician Management	Physician Management Plus Cognitive Behavioral Therapy
Arm/Group Description	Physician management was provided during fifteen to twenty minute sessions by Internal Medicine physicians with experience providing buprenorphine. Sessions occurred weekly for the first two weeks, every two weeks for the next four weeks, then monthly. During physician management the physician followed a structured note that reviewed the patient’s recent drug use, provided brief advice on how to achieve or maintain abstinence, supported efforts to reduce drug use or remain abstinent, reviewed medical and psychiatric complaints, assessed social, work and legal function, discussed weekly urine toxicology results and reviewed attendance at self-help groups.	In addition to recieving Physician Management identical to the Physician Management only condition, patients were offered up to 12, 50-minute weekly sessions during the first 12 weeks of treatment. Cognitive behavioral therapy was provided by masters- and doctoral-level clinicians who were trained to competence using a manual adapted from the use of cognitive behavioral therapy for cocaine dependence. To ensure fidelity, all sessions were audio- or video-taped, and clinicians underwent weekly supervision. The main components of counseling focused on a functional analysis of behavior, behavioral activation, identifying and coping with drug cravings, enhancing drug-refusal skills, enhancing decision making about high-risk situations and improve problem-solving skills.
Period Title: Overall Study
Started	71	70
Completed	32	27
Not Completed	39	43
Reason Not Completed
Protocol Violation	24	19
Missed Medication >1 week	10	17
Missed 3 PM visits	1	7
Withdrawal by Subject	4	0

Baseline Characteristics

Arm/Group Title		Physician Management	Physician Management Plus Cognitive Behavioral Therapy	Total
Arm/Group Description		Physician management was provided during fifteen to twenty minute sessions by Internal Medicine physicians with experience providing buprenorphine. Sessions occurred weekly for the first two weeks, every two weeks for the next four weeks, then monthly. During physician management the physician followed a structured note that reviewed the patient’s recent drug use, provided brief advice on how to achieve or maintain abstinence, supported efforts to reduce drug use or remain abstinent, reviewed medical and psychiatric complaints, assessed social, work and legal function, discussed weekly urine toxicology results and reviewed attendance at self-help groups.	In addition to receiving Physician Management identical to the Physician Management only condition, patients were offered up to 12, 50-minute weekly sessions during the first 12 weeks of treatment. Cognitive behavioral therapy was provided by masters- and doctoral-level clinicians who were trained to competence using a manual adapted from the use of cognitive behavioral therapy for cocaine dependence. To ensure fidelity, all sessions were audio- or video-taped, and clinicians underwent weekly supervision. The main components of counseling focused on a functional analysis of behavior, behavioral activation, identifying and coping with drug cravings, enhancing drug-refusal skills, enhancing decision making about high-risk situations and improve problem-solving skills.	Total of all reporting groups
Overall Number of Baseline Participants		71	70	141
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	71 participants	70 participants	141 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	71 100.0%	70 100.0%	141 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	71 participants	70 participants	141 participants
		34.5 (10.3)	32.8 (8.6)	33.6 (9.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	71 participants	70 participants	141 participants
	Female	18 25.4%	19 27.1%	37 26.2%
	Male	53 74.6%	51 72.9%	104 73.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	71 participants	70 participants	141 participants
		71	70	141

Outcome Measures

1. Primary Outcome

Title	Illicit Opioid Abstinence
Description	number of weeks of abstinence from illicit opioids, as documented by urine toxicology and self-report. Range 0 - 24.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Repeated measures analysis of variance was used to evaluate differences between groups in the maximum number of consecutive weeks of opioid abstinence for the first and second 12 weeks of treatment. We coded missing urine specimens as positive for opioids in our analysis, thus all participants provided data.

Arm/Group Title	Physician Management	Physician Management Plus Cognitive Behavioral Therapy
Arm/Group Description:	Physician management was provided during fifteen to twenty minute sessions by Internal Medicine physicians with experience providing buprenorphine. Sessions occurred weekly for the first two weeks, every two weeks for the next four weeks, then monthly. During physician management the physician followed a structured note that reviewed the patient's recent drug use, provided brief advice on how to achieve or maintain abstinence, supported efforts to reduce drug use or remain abstinent, reviewed medical and psychiatric complaints, assessed social, work and legal function, discussed weekly urine toxicology results and reviewed attendance at self-help groups.	In addition to receiving Physician Management identical to the Physician Management only condition, patients were offered up to 12, 50-minute weekly sessions during the first 12 weeks of treatment. Cognitive behavioral therapy was provided by masters- and doctoral-level clinicians who were trained to competence using a manual adapted from the use of cognitive behavioral therapy for cocaine dependence. To ensure fidelity, all sessions were audio- or video-taped, and clinicians underwent weekly supervision. The main components of counseling focused on a functional analysis of behavior, behavioral activation, identifying and coping with drug cravings, enhancing drug-refusal skills, enhancing decision making about high-risk situations and improve problem-solving skills.
Overall Number of Participants Analyzed	71	70
Mean (Standard Deviation); Unit of Measure: Weeks of Abstinence
	10.29 (8.48)	10.12 (8.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Physician Management, Physician Management Plus Cognitive Behavioral Therapy
	Comments	With an effect size of 0.46, a sample size of 140 will provide a power of >.84 with p<.05 to detect overall differences between the two treatments on the primary outcome measures.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.91
	Comments	[Not Specified]
	Method	ANOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.16
	Parameter Dispersion	Type: Standard Error of the mean; Value: 1.40
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Treatment Completion
Description	The number of patients who completed the study (did not meet the criteria for protective transfer baseed on drug use, did not miss medication for more than seven days, or did not miss three or more Physician Management sessions) at 24 weeks.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All participants who entered treatment were evaluated for treatment completion.

Arm/Group Title	Physician Management	Physician Management Plus Cognitive Behavioral Therapy
Arm/Group Description:	Physician management was provided during fifteen to twenty minute sessions by Internal Medicine physicians with experience providing buprenorphine. Sessions occurred weekly for the first two weeks, every two weeks for the next four weeks, then monthly. During physician management the physician followed a structured note that reviewed the patient's recent drug use, provided brief advice on how to achieve or maintain abstinence, supported efforts to reduce drug use or remain abstinent, reviewed medical and psychiatric complaints, assessed social, work and legal function, discussed weekly urine toxicology results and reviewed attendance at self-help groups.	In addition to receiving Physician Management identical to the Physician Management only condition, patients were offered up to 12, 50-minute weekly sessions during the first 12 weeks of treatment. Cognitive behavioral therapy was provided by masters- and doctoral-level clinicians who were trained to competence using a manual adapted from the use of cognitive behavioral therapy for cocaine dependence. To ensure fidelity, all sessions were audio- or video-taped, and clinicians underwent weekly supervision. The main components of counseling focused on a functional analysis of behavior, behavioral activation, identifying and coping with drug cravings, enhancing drug-refusal skills, enhancing decision making about high-risk situations and improve problem-solving skills.
Overall Number of Participants Analyzed	71	70
Measure Type: Number; Unit of Measure: participants
	45	39

3. Secondary Outcome

Title	Cocaine Abstinence
Description	Total weeks of cocaine abstinence as documented by weekly urine toxicology analysis. Range from 0 to 24.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All participants provided one or more urine screens thus data was based on all participants.

Arm/Group Title	Physician Management	Physician Management Plus Cognitive Behavioral Therapy
Arm/Group Description:	Physician management was provided during fifteen to twenty minute sessions by Internal Medicine physicians with experience providing buprenorphine. Sessions occurred weekly for the first two weeks, every two weeks for the next four weeks, then monthly. During physician management the physician followed a structured note that reviewed the patient's recent drug use, provided brief advice on how to achieve or maintain abstinence, supported efforts to reduce drug use or remain abstinent, reviewed medical and psychiatric complaints, assessed social, work and legal function, discussed weekly urine toxicology results and reviewed attendance at self-help groups.	In addition to receiving Physician Management identical to the Physician Management only condition, patients were offered up to 12, 50-minute weekly sessions during the first 12 weeks of treatment. Cognitive behavioral therapy was provided by masters- and doctoral-level clinicians who were trained to competence using a manual adapted from the use of cognitive behavioral therapy for cocaine dependence. To ensure fidelity, all sessions were audio- or video-taped, and clinicians underwent weekly supervision. The main components of counseling focused on a functional analysis of behavior, behavioral activation, identifying and coping with drug cravings, enhancing drug-refusal skills, enhancing decision making about high-risk situations and improve problem-solving skills.
Overall Number of Participants Analyzed	71	70
Mean (Standard Deviation); Unit of Measure: weeks of abstinence
	12.4 (7.7)	13.8 (7.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Physician Management, Physician Management Plus Cognitive Behavioral Therapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.29
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.40
	Parameter Dispersion	Type: Standard Error of the mean; Value: 1.32
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Criminal Activity- Addiction Severity Index (ASI) Legal Composite Score.
Description	The ASI Legal Composite score ranges from 0 to 1 with higher scores corresponding to greater legal problems.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All participants who completed one or more ASI assessments were included in the analysis.

Arm/Group Title	Physician Management	Physician Management Plus Cognitive Behavioral Therapy
Arm/Group Description:	Physician management was provided during fifteen to twenty minute sessions by Internal Medicine physicians with experience providing buprenorphine. Sessions occurred weekly for the first two weeks, every two weeks for the next four weeks, then monthly. During physician management the physician followed a structured note that reviewed the patient's recent drug use, provided brief advice on how to achieve or maintain abstinence, supported efforts to reduce drug use or remain abstinent, reviewed medical and psychiatric complaints, assessed social, work and legal function, discussed weekly urine toxicology results and reviewed attendance at self-help groups.	In addition to receiving Physician Management identical to the Physician Management only condition, patients were offered up to 12, 50-minute weekly sessions during the first 12 weeks of treatment. Cognitive behavioral therapy was provided by masters- and doctoral-level clinicians who were trained to competence using a manual adapted from the use of cognitive behavioral therapy for cocaine dependence. To ensure fidelity, all sessions were audio- or video-taped, and clinicians underwent weekly supervision. The main components of counseling focused on a functional analysis of behavior, behavioral activation, identifying and coping with drug cravings, enhancing drug-refusal skills, enhancing decision making about high-risk situations and improve problem-solving skills.
Overall Number of Participants Analyzed	67	64
Mean (Standard Error); Unit of Measure: Scores on a scale
	.044 (.011)	.066 (.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Physician Management, Physician Management Plus Cognitive Behavioral Therapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.58
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Mixed Model Analysis to evaluate interaction of group by time.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	.04
	Parameter Dispersion	Type: Standard Error of the mean; Value: .029
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Overall Health- Short Form (36) Health Survey
Description	Short Form (36) Health Survey overall score ranges from 0 to 100. Computed as the mean of all SF-36 subscales. The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. Lower scores are greater disability and higher scores are greater health functioning.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

All participants who completed 1 or more SF-36 assessments were included in the analysis.

Arm/Group Title	Physician Management	Physician Management Plus Cognitive Behavioral Therapy
Arm/Group Description:	Physician management was provided during fifteen to twenty minute sessions by Internal Medicine physicians with experience providing buprenorphine. Sessions occurred weekly for the first two weeks, every two weeks for the next four weeks, then monthly. During physician management the physician followed a structured note that reviewed the patient's recent drug use, provided brief advice on how to achieve or maintain abstinence, supported efforts to reduce drug use or remain abstinent, reviewed medical and psychiatric complaints, assessed social, work and legal function, discussed weekly urine toxicology results and reviewed attendance at self-help groups.	In addition to receiving Physician Management identical to the Physician Management only condition, patients were offered up to 12, 50-minute weekly sessions during the first 12 weeks of treatment. Cognitive behavioral therapy was provided by masters- and doctoral-level clinicians who were trained to competence using a manual adapted from the use of cognitive behavioral therapy for cocaine dependence. To ensure fidelity, all sessions were audio- or video-taped, and clinicians underwent weekly supervision. The main components of counseling focused on a functional analysis of behavior, behavioral activation, identifying and coping with drug cravings, enhancing drug-refusal skills, enhancing decision making about high-risk situations and improve problem-solving skills.
Overall Number of Participants Analyzed	70	69
Mean (Standard Error); Unit of Measure: Scores on a scale
	75.3 (1.7)	75.1 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Physician Management, Physician Management Plus Cognitive Behavioral Therapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.24
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Mixed Model Analysis to evaluate interaction of group by time.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.38
	Parameter Dispersion	Type: Standard Error of the mean; Value: 3.63
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Physician Management	Physician Management Plus Cognitive Behavioral Therapy
Arm/Group Description	Physician management was provided during fifteen to twenty minute sessions by Internal Medicine physicians with experience providing buprenorphine. Sessions occurred weekly for the first two weeks, every two weeks for the next four weeks, then monthly. During physician management the physician followed a structured note that reviewed the patient’s recent drug use, provided brief advice on how to achieve or maintain abstinence, supported efforts to reduce drug use or remain abstinent, reviewed medical and psychiatric complaints, assessed social, work and legal function, discussed weekly urine toxicology results and reviewed attendance at self-help groups.	In addition to recieving Physician Management identical to the Physician Management only condition, patients were offered up to 12, 50-minute weekly sessions during the first 12 weeks of treatment. Cognitive behavioral therapy was provided by masters- and doctoral-level clinicians who were trained to competence using a manual adapted from the use of cognitive behavioral therapy for cocaine dependence. To ensure fidelity, all sessions were audio- or video-taped, and clinicians underwent weekly supervision. The main components of counseling focused on a functional analysis of behavior, behavioral activation, identifying and coping with drug cravings, enhancing drug-refusal skills, enhancing decision making about high-risk situations and improve problem-solving skills.
All-Cause Mortality
	Physician Management	Physician Management Plus Cognitive Behavioral Therapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Physician Management	Physician Management Plus Cognitive Behavioral Therapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/71 (0.00%)	0/70 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Physician Management	Physician Management Plus Cognitive Behavioral Therapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/71 (0.00%)	0/70 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

Results Point of Contact

Name/Title: Dr. David Fiellin

Organization: Yale University

Phone: 203-737-3347

EMail: david.fiellin@yale.edu

Publications of Results:

Fiellin DA, Barry DT, Sullivan LE, Cutter CJ, Moore BA, O'Connor PG, Schottenfeld RS. A randomized trial of cognitive behavioral therapy in primary care-based buprenorphine. Am J Med. 2013 Jan;126(1):74.e11-7. doi: 10.1016/j.amjmed.2012.07.005.

Responsible Party:	David Fiellin, Yale University
ClinicalTrials.gov Identifier:	NCT00595764 History of Changes
Obsolete Identifiers:	NCT00632151
Other Study ID Numbers:	5R01DA019511 ( U.S. NIH Grant/Contract ); 5R01DA019511 ( U.S. NIH Grant/Contract )
First Submitted:	October 3, 2007
First Posted:	January 16, 2008
Results First Submitted:	July 18, 2013
Results First Posted:	October 6, 2014
Last Update Posted:	October 6, 2014