Buprenorphine and Substance Abuse Services for Prescription Opioid Dependence

Study Overview
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Brief Summary
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This is a randomized trial of two group-based models of care for buprenorphine/naloxone (bup/nx) patients in Substance Use (SU) specialty treatment: Standard Medical Management (SMM) and Intensive Outpatient Treatment (IOT). The setting is a large outpatient SU treatment program, where a medical management model of care has not been empirically tested with bup/nx patients, and where a high prevalence of patients with co-occurring psychiatric and medical co-morbidities are treated. SSM includes brief weekly group-based visits consistent with previously studied medical models, and is drawn from primary care bup/nx research. IOT is a predominant model of care in specialty treatment, and incorporates psychosocial support, 12-step, educational and relapse-prevention based approaches. The investigators will recruit 300 adult patients inducted onto bup/nx, randomize them to either SMM or IOT, and conduct telephone follow-up interviews at 6 and 12 months. Study investigators will examine the impact of these treatment approaches on 90-day bup/nx adherence, opioid and SU abstinence, quality of life, and health care and societal costs. Further, investigators will examine whether the effect of IOT versus SMM on adherence and SU treatment outcomes is greater for those with medical or psychiatric co-morbidities. This innovative approach includes a focus on complex patients with psychiatric and medical co-morbidities in specialty care, adapting a care model previously only tested in primary care, a 12-month follow-up, no research-forced medication taper, an examination of health care and societal costs, and a combination of patient self-report and electronic medical record data. Through this approach, the proposed study will yield critically important findings on how best to treat complex prescription opioid dependent patients with an integrative behavioral services and medication treatment model in SU treatment.

Detailed Description
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The study will contrast and compare the effectiveness and costs of two forms of behavioral SU treatment services for a total of 300 opioid dependent patients seeking bup/nx treatment at the Kaiser Sacramento Chemical Dependency Recovery Program (CDRP). The design is a between-groups clinical trial using blocked randomization to the two treatments (IOT and SMM) with analyses based on an intent-to-treat model. Patients are recruited into the study and randomized after induction at the time of program intake. A full battery of background, concurrent status and diagnostic information will be collected at baseline, and repeated 6 and 12 months later to assess change in drug use, 30 day and 6-month abstinence, and quality of life at each point. The study will test for illicit drug use and presence of buprenorphine with random urinalysis throughout treatment. In addition to urinalysis, bup/nx adherence will be measured using prescription drug refills and self-report. Investigators will collect self-report of prescription opioid use and abstinence. Finally, the number and types of services received by during treatment will be available from the EMR. Patients seeking bup/nx receive a 30-minute medical exam from a CDRP physician (e.g., for symptoms of alcohol or other drug withdrawal, hypertension, acute infections related to intravenous drug use, mental status, acute psychosis or suicidal tendencies) to assess appropriateness for bup/nx and discuss the treatment. After this initial evaluation, the induction is managed by the clinic nurse, in consultation with a clinic physician. Induction follows the standard of care, and occurs over 2-3 days. The average daily dose of bup/nx ranges from 12-24mg, but is typically 16 mg. After induction, the patient will be scheduled for an intake interview for admission into the treatment program. Following the intake session, a research staff member will describe the study and assess eligibility criteria. For patients who agree to participate, the research associate will proceed to enroll the patient in a private room. During enrollment/baseline appointment, the research associate will obtain informed consent and administer a baseline questionnaire using a laptop computer (see below). Patients will then be randomized to either the IOT or SMM arm using a block randomization procedure which will ensure that equal numbers of patients will be assigned to each treatment arm. Patients unwilling or unable to be randomized will meet with the intake therapist and treated in the standard manner designated by the treatment program's regular intake counselors, and will not be part of the study. At baseline, following recruitment and consent, participants will complete a computerized interview in a private place at the CDRP (with a research associate available for any computer or content questions). A full battery of background, physical and mental health and SU disorder information will be collected. Study investigators will conduct two follow-up telephone interviews whether or not patients complete the CDRP treatment program. At the follow-up, participants will be reminded of the study and permission to conduct the interview will be obtained verbally. Interviews will be conducted at 6 and 12 months by research staff with the same baseline measures to assess treatment adherence, substance use and abstinence, and quality of life. Also, patients will be asked to present at the CDRP within 48 hours of the 6 and 12 month interviews for a urine test and additional brief questions on drug use.

Official Title
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Buprenorphine and Substance Abuse Services for Prescription Opioid Dependence

Conditions
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Opiate Substitution Treatment

Intervention / Treatment
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* Behavioral: Standard Medical Management (SMM)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: inducted for buprenorphine/naloxone treatment at the Sacramento CDRP diagnosis of opioid dependence English speaking Willing and able to be randomized to treatment arm Exclusionary criteria: dementia mental retardation actively psychotic or suicidal medically unstable using opioids pregnant women inducted on bup/nx for chronic pain inducted on bup/nx for detoxification purposes only enrolled in DDIOP, residential treatment or day treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standard Medical Management<br>Standard Medical Management (SMM) is a relatively brief (1.5 hour per week for 9 weeks), medically-focused behavioral intervention for opioid dependence. The experimental arm does not involve an investigational drug, device, or biologic. | Behavioral: Standard Medical Management (SMM)<br>* SMM is designed to provide basic advice about opioid dependence and encouragement to adhere to treatment recommendations. Sessions provide support and monitoring of medication compliance, dose, withdrawal, adverse effects, and discussion of medical complications of opioid and other drug use. Early in treatment, the focus will be on helping patients adjust to the medications (e.g., monitoring withdrawal or other adverse symptoms, tolerating discomfort, curtailing illicit drug use, and referral to self-help). As treatment progresses, the practitioner may focus more on educating the patient about the social and behavioral factors perpetuating addiction and encourage behavioral and lifestyle change to support recovery.<br>|
| No Intervention: Intensive Outpatient Treatment<br>The Intensive Outpatient Treatment (IOT) arm is considered usual care and is a predominant model of care in specialty treatment. It incorporates psychosocial support, education, and relapse-prevention approaches and requires attendance at 12-step program. It is a group-based treatment, with individual counseling available as needed. During the initial, 3-week phase, treatment consists of 4-6 hours a day, 7 days a week. In weeks four through 9, treatment consists of 1.5 hours, four days each week. After 9 weeks, patients attend one-hour weekly group meetings for one year. Services include supportive therapy, psycho-education, relapse prevention, and family-oriented therapy. The program emphasis is on abstinence and is similar to many public and private intensive outpatient programs. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to buprenorphine/naloxone using MPR | Buprenorphine/naloxone adherence will be measured using KPNC's pharmacy database. Adherence will be based on prescription refills and calculated using Medication Possession Ratio methods, similar to other published KPNC studies which have measured adherence as a key outcome variable. Adherence will be defined as the patient having medication available on 80% or more of the 90 day period-that is, an MPR of .8 or higher. | 90-day | 
| Abstinence using ASI | We use composite measures from the Addiction Severity (ASI) index to examine 30 day abstinence outcomes for opioids and other substances (marijuana, cocaine, methamphetamine and other stimulants, hallucinogens, barbiturates, tranquilizers, inhalants, hallucinogens). | 6 months | 
| Health care utilization costs using ICER | Substance use treatment utilization data (number of visits, number of days in treatment), as well as general health care utilization data (inpatient, outpatient, and ER) will be collected using the electronic medical record. In addition, health care utilization outside Kaiser will be assessed and used to create composite measure of health care utilization costs. The incremental cost-effectiveness ratio (ICER) will be calculated for each additional unit of outcome as the ratio of difference in costs between the two arms divided by the difference in outcome. | 12 months | 
| Adherence to buprenorphine/naloxone using drug testing | Urine tests will be performed weekly during treatment. If 80% of test results within the 90-day period are positive during the 90 day period, we will consider the patient to be adherent to treatment. | 90-day | 
| Abstinence using ASI | We use composite measures from the Addiction Severity (ASI) index to examine 30 day abstinence outcomes for opioids and other substances (marijuana, cocaine, methamphetamine and other stimulants, hallucinogens, barbiturates, tranquilizers, inhalants, hallucinogens). | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic Pain using the pain Interference scale | The severity of chronic pain and the degree to which it interferes with every day life will be measured using the PROMIS Pain Interference scale. | 6 months | 
| Quality of Life using PROMIS Global Health scale | Quality of life will be assessed by the PROMIS Global Health scale, which measures satisfaction with physical health, psychological health, and social relationships. | 6 months | 
| Mental health using PHQ-9 | Psychiatric problem severity will be measured by the PHQ-9, a 9-item measure of depression and anxiety symptoms. | 6 months | 
| Chronic Pain using the pain Interference scale | The severity of chronic pain and the degree to which it interferes with every day life will be measured using the PROMIS Pain Interference scale. | 12 months | 
| Mental health using PHQ-9 | Psychiatric problem severity will be measured by the PHQ-9, a 9-item measure of depression and anxiety symptoms. | 12 months | 
| Quality of Life using PROMIS Global Health scale | Quality of life will be assessed by the PROMIS Global Health scale, which measures satisfaction with physical health, psychological health, and social relationships. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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buprenorphine-naloxone combination, Suboxone, Buprenorphine, Substance Use, Behavioral intervention, Opioid partial agonist, medication assisted therapy, opioid addiction