POD: Clinical Trial of Integrated Treatment for Pain and Opioid Dependence

• Sponsor: Yale University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00634803
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 90
• Location: 1
• Arms: 3
• Duration (Months): 71
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This study is designed to develop an effective psychotherapy for chronic pain and opioid dependence.

Condition or Disease	Intervention/Treatment	Phase
Opiate Dependence; Chronic Pain	Behavioral: CBT; Drug: Buprenorphine; Other: Educational Counseling; Other: Physician Management	Phase 1/Phase 2

Detailed Description

This study aims to develop a novel manualized intervention using tailored cognitive-behavioral treatment (CBT) and buprenorphine medication to effectively treat the co-occurring disorders of non-malignant pain and opioid dependence (POD).

Specific Aims:

1. To conduct a pre-pilot phase with 16 patients with POD receiving buprenorphine maintenance treatment (BMT). In the pre-pilot phase, we will also explore the effects of different daily buprenorphine dosages on pain and opiate use.

2. To conduct a pilot randomized, clinical trial to obtain data regarding the feasibility, acceptability and efficacy (compared to Physician Management(PM) only) of manual-guided CBT or Educational Counseling (EC) for patients with POD treated with BMT (N=75).

The secondary outcomes: Development of a Treatment Manual and Development and Modification of Initial Therapy Training and Process Rating Measures were process measures and not been to be included as measures associated with RCT. These outcomes were removed when the RCT results were entered. In addition, outcomes were renamed for clarification.

At results entry, the timeframe (16 weeks) was also corrected to account for the actual timeframe used for analysis in the study. The 16-week study period listed in the protocol included a 2-week buprenorphine induction period (before randomization) and up to a 2-week post-conclusion of the clinical trial continuation on buprenorphine and referral to continuing treatment. In prior studies with buprenorphine, the study team had observed an artificially high attrition during the last 2 weeks of the planned study protocol, when participants were attempting to transition to available clinical treatments outside of the study. Consequently, as per the original study protocol for this study, the plan was to analyze intake and induction data (as baseline data) and then the data from the first 12-weeks post-randomization.

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Trial of Integrated Treatment for Pain and Opioid Dependence
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CBT for POD Integrated cognitive behavioral therapy for chronic pain and opioid dependence	Behavioral: CBT; Cognitive behavioral therapy; Drug: Buprenorphine; buprenorphine/naloxone
Active Comparator: Educational Counseling for POD Educational Counseling is a didactic, lecture-discussion format to supplement the information and advice provided by physicians in physician management (PM)	Drug: Buprenorphine; buprenorphine/naloxone; Other: Educational Counseling; Didactic, lecture-discussion format to supplement information and advice provided by physicians
Active Comparator: Physician Management PM is a relatively brief intervention that approximates the medically focused advice and brief counseling about medical issues that is typically provided by physicians to patients with chronic pain or other chronic medical conditions, such as diabetes or asthma.	Drug: Buprenorphine; buprenorphine/naloxone; Other: Physician Management; Brief physician counseling

Outcome Measures

Primary Outcome Measures

1. Pain Intensity [3 months]

   Pain intensity comprises the average of 4 items related to current pain and past-week average pain, pain at its worst, and pain at its least. Pain intensity is scored on 0-10 scale (average score ranges from 0-10), where higher scores indicate higher pain intensity.Originally labeled as Pain Reduction at 16 weeks- 3 months was the correct timeframe.

2. Number of Opioid-negative Urine Toxicology Tests [3 Months]

   Reduced illicit opioid use is defined as the number of documented opioid negative urine tests in each of the time periods.This measures the reduction in illicit opioid use - more opioid-negative tests means greater reductions in illicit opioid use. The highest possible score is 4- which would indicate 4 negative urine tests during the assessment period. Originally titled "Reduced illicit opioid use" and the timeframe was listed as 16 weeks.

3. Pain Interference [3 Months]

   Pain interference comprises the average of 7 items related to past-week pain-related interference in general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. Each item is scored on a 0-10 scale (averaged 0-10), where higher scores indicate higher pain interference.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• 18 years of age or older

• prescription opioid addiction criteria

• moderate to severe chronic pain

• seeking or interested in buprenorphine maintenance

• understand English

Exclusion Criteria:

• methadone maintenance at a dose greater than 40 mg daily

• current suicide or homicide risk

• life-threatening or unstable medical problem

• pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Methadone Research Unit	New Haven	Connecticut	United States	06519

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Richard S Schottenfeld, MD, Yale University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yale University
• ClinicalTrials.gov Identifier: NCT00634803
• Other Study ID Numbers: 0608001776; 1R01DA024695-01A2
• First Posted: Mar 13, 2008
• Last Update Posted: Aug 2, 2021
• Last Verified: Jul 1, 2021

• Additional relevant MeSH terms: Chronic Pain; Opioid-Related Disorders; Buprenorphine

Study Results

Participant Flow

Arm/Group Title	CBT for POD	Educational Counseling for POD	Physician Management
Arm/Group Description	Integrated cognitive behavioral therapy for chronic pain and opioid dependence CBT: Cognitive behavioral therapy Buprenorphine: buprenorphine/naloxone	Educational Counseling is a didactic, lecture-discussion format to supplement the information and advice provided by physicians in physician management (PM) Buprenorphine: buprenorphine/naloxone Educational Counseling: Didactic, lecture-discussion format to supplement information and advice provided by physicians	PM is a relatively brief intervention that approximates the medically focused advice and brief counseling about medical issues that is typically provided by physicians to patients with chronic pain or other chronic medical conditions, such as diabetes or asthma. Buprenorphine: buprenorphine/naloxone Physician Management: Brief physician counseling
Period Title: Overall Study
STARTED	30	30	30
Month 1	29	29	29
Month 2	26	26	28
Month 3	25	23	26
COMPLETED	24	23	23
NOT COMPLETED	6	7	7

Baseline Characteristics

Arm/Group Title	CBT for POD	Educational Counseling for POD	Physician Management	Total
Arm/Group Description	Integrated cognitive behavioral therapy for chronic pain and opioid dependence CBT: Cognitive behavioral therapy Buprenorphine: buprenorphine/naloxone	Educational Counseling is a didactic, lecture-discussion format to supplement the information and advice provided by physicians in physician management (PM) Buprenorphine: buprenorphine/naloxone Educational Counseling: Didactic, lecture-discussion format to supplement information and advice provided by physicians	PM is a relatively brief intervention that approximates the medically focused advice and brief counseling about medical issues that is typically provided by physicians to patients with chronic pain or other chronic medical conditions, such as diabetes or asthma. Buprenorphine: buprenorphine/naloxone Physician Management: Brief physician counseling	Total of all reporting groups
Overall Participants	30	30	30	90
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	30 100%	30 100%	30 100%	90 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.3 (9.4)	37.0 (9.9)	35.3 (10.00)	35.8 (9.8)
Sex: Female, Male (Count of Participants)
Female	19 63.3%	10 33.3%	10 33.3%	39 43.3%
Male	11 36.7%	20 66.7%	20 66.7%	51 56.7%
Region of Enrollment (participants) [Number]
United States	30 100%	30 100%	30 100%	90 100%

Outcome Measures

1. Primary Outcome

Title	Pain Intensity
Description	Pain intensity comprises the average of 4 items related to current pain and past-week average pain, pain at its worst, and pain at its least. Pain intensity is scored on 0-10 scale (average score ranges from 0-10), where higher scores indicate higher pain intensity.Originally labeled as Pain Reduction at 16 weeks- 3 months was the correct timeframe.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

The analysis population is the intention to treat population and all observations across time periods were used in the analysis.

Arm/Group Title	CBT for POD	Educational Counseling for POD	Physician Management
Arm/Group Description	Integrated cognitive behavioral therapy for chronic pain and opioid dependence CBT: Cognitive behavioral therapy Buprenorphine: buprenorphine/naloxone	Educational Counseling is a didactic, lecture-discussion format to supplement the information and advice provided by physicians in physician management (PM) Buprenorphine: buprenorphine/naloxone Educational Counseling: Didactic, lecture-discussion format to supplement information and advice provided by physicians	PM is a relatively brief intervention that approximates the medically focused advice and brief counseling about medical issues that is typically provided by physicians to patients with chronic pain or other chronic medical conditions, such as diabetes or asthma. Buprenorphine: buprenorphine/naloxone Physician Management: Brief physician counseling
Measure Participants	30	30	30
Intake/Induction	5.43 (1.34)	5.92 (1.57)	5.28 (1.34)
Month 1	4.75 (1.62)	5.02 (1.45)	4.53 (1.46)
Month 2	4.79 (1.50)	4.98 (1.76)	4.72 (1.81)
Month 3	4.41 (1.67)	4.62 (1.91)	4.84 (1.91)

2. Primary Outcome

Title	Number of Opioid-negative Urine Toxicology Tests
Description	Reduced illicit opioid use is defined as the number of documented opioid negative urine tests in each of the time periods.This measures the reduction in illicit opioid use - more opioid-negative tests means greater reductions in illicit opioid use. The highest possible score is 4- which would indicate 4 negative urine tests during the assessment period. Originally titled "Reduced illicit opioid use" and the timeframe was listed as 16 weeks.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

The analysis population is the intention to treat population and all observations across time periods were used in the analysis. Participants may have contributed to this outcome but were lost to follow up during the time period and were not measured on pain related outcomes.

Arm/Group Title	CBT for POD	Educational Counseling for POD	Physician Management
Arm/Group Description	Integrated cognitive behavioral therapy for chronic pain and opioid dependence CBT: Cognitive behavioral therapy Buprenorphine: buprenorphine/naloxone	Educational Counseling is a didactic, lecture-discussion format to supplement the information and advice provided by physicians in physician management (PM) Buprenorphine: buprenorphine/naloxone Educational Counseling: Didactic, lecture-discussion format to supplement information and advice provided by physicians	PM is a relatively brief intervention that approximates the medically focused advice and brief counseling about medical issues that is typically provided by physicians to patients with chronic pain or other chronic medical conditions, such as diabetes or asthma. Buprenorphine: buprenorphine/naloxone Physician Management: Brief physician counseling
Measure Participants	30	30	30
Intake/Induction	0.67 (0.55)	0.67 (0.48)	0.55 (0.69)
Month 1	2.67 (1.42)	2.80 (1.27)	2.48 (1.70)
Month 2	2.96 (1.48)	3.30 (1.14)	2.56 (1.72)
Month 3	2.80 (1.38)	3.25 (1.22)	2.04 (1.71)

3. Primary Outcome

Title	Pain Interference
Description	Pain interference comprises the average of 7 items related to past-week pain-related interference in general activity, walking, work, mood, enjoyment of life, relations with others, and sleep. Each item is scored on a 0-10 scale (averaged 0-10), where higher scores indicate higher pain interference.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

The analysis population is the intention to treat population and all observations across time periods were used in the analysis.

Arm/Group Title	CBT for POD	Educational Counseling for POD	Physician Management
Arm/Group Description	Integrated cognitive behavioral therapy for chronic pain and opioid dependence CBT: Cognitive behavioral therapy Buprenorphine: buprenorphine/naloxone	Educational Counseling is a didactic, lecture-discussion format to supplement the information and advice provided by physicians in physician management (PM) Buprenorphine: buprenorphine/naloxone Educational Counseling: Didactic, lecture-discussion format to supplement information and advice provided by physicians	PM is a relatively brief intervention that approximates the medically focused advice and brief counseling about medical issues that is typically provided by physicians to patients with chronic pain or other chronic medical conditions, such as diabetes or asthma. Buprenorphine: buprenorphine/naloxone Physician Management: Brief physician counseling
Measure Participants	30	30	30
Intake/Induction	5.75 (2.12)	5.48 (2.23)	5.01 (2.19)
Month 1	4.15 (2.09)	3.74 (1.82)	3.32 (2.12)
Month 2	4.08 (2.06)	3.61 (1.97)	3.45 (2.45)
Month 3	3.22 (1.94)	3.23 (2.27)	3.87 (2.56)

Adverse Events

Time Frame	Up to the end of study (month 3)
Arm/Group Title	CBT for POD		Educational Counseling for POD		Physician Management
Arm/Group Description	Integrated cognitive behavioral therapy for chronic pain and opioid dependence CBT: Cognitive behavioral therapy Buprenorphine: buprenorphine/naloxone		Educational Counseling is a didactic, lecture-discussion format to supplement the information and advice provided by physicians in physician management (PM) Buprenorphine: buprenorphine/naloxone Educational Counseling: Didactic, lecture-discussion format to supplement information and advice provided by physicians		PM is a relatively brief intervention that approximates the medically focused advice and brief counseling about medical issues that is typically provided by physicians to patients with chronic pain or other chronic medical conditions, such as diabetes or asthma. Buprenorphine: buprenorphine/naloxone Physician Management: Brief physician counseling
All Cause Mortality
	CBT for POD		Educational Counseling for POD		Physician Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)		0/30 (0%)
Serious Adverse Events
	CBT for POD		Educational Counseling for POD		Physician Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	CBT for POD		Educational Counseling for POD		Physician Management
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/30 (0%)		0/30 (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.