Buprenorphine and Methadone for Opioid-dependent Chronic Back Pain Patients

• ClinicalTrials.gov Identifier: NCT01559454
• Recruitment Status: Completed
• First Posted: March 21, 2012
• Results First Posted: February 20, 2017
• Last Update Posted: February 20, 2017
• Sponsor: State University of New York at Buffalo
• Information provided by (Responsible Party): State University of New York at Buffalo

Study Description

Brief Summary:

Chronic pain patients are treated with prescription opioids and many exhibit opioid addiction. Currently, there are no evidence-based guidelines to better manage patients with chronic pain and coexistent opioid addiction. This study compares 6-months buprenorphine and methadone treatment in these patients. The investigators hypothesize that both buprenorphine and methadone treatment will reduce pain and addiction behaviors and increase functioning in these patients.

Condition or disease	Intervention/treatment	Phase
Low Back Pain	Drug: Methadone; Drug: Buprenorphine/naloxone	Phase 4

Detailed Description:

Chronic non-malignant pain (i.e. pain unrelated to cancer that persists beyond the usual course of disease or injury) is a major concern in the United States. Opioids are the most commonly prescribed medication to treat patients with chronic non-malignant pain. However, in one systematic review of chronic low back pain, the authors note that, although clinical trials suggest that opioids are effective for short-term use (≤ 16 weeks), the effectiveness of long-term opioids (> 16 weeks) for pain relief and improved physical functioning is less clear.

Five to 31 percent of chronic back pain patients prescribed long-term opioids show aberrant drug-taking behaviors. Many develop tolerance and withdrawal, 43% of these patients exhibit opioid addiction. Therefore, patients with chronic pain and a co-occurring opioid addiction present a clinical challenge. In such cases, referral to addiction experts is recommended, but specialized treatment is currently based on expert opinion and observational studies.

The expert recommendation is detoxification followed by treatment with methadone, buprenorphine, naltrexone, or non-opioid analgesics in conjunction with behavioral counseling. Discontinuing short-acting opioid medications increases pain and will make it difficult for these patients to abstain from opioids due to the severity of pain. However, continuing these opioid medications worsens their addiction and renders opioids ineffective in the treatment of pain. Research is needed to compare the various medication-assisted treatments.

Long-acting opioids (e.g., methadone, buprenorphine) are used to replace treatment with short-acting opioids (e.g., hydrocodone, oxycodone). Methadone is a full mu-opioid-receptor agonist that can be effective in treating pain. Two small studies suggest that treatment of patients with chronic pain and co-occurring substance use disorder with methadone and adjunctive pain management therapy is superior to non-opioid treatment protocols. Despite the demonstration that methadone can be effective as both an analgesic and for opioid addiction treatment, it possesses side effects (e.g, constipation) and serious adverse events (e.g, respiratory depression, risk of overdose) that limit its use, making physicians reluctant to prescribe methadone.

Buprenorphine, a partial opioid agonist, is an alternative to methadone for treatment of opioid addiction, has a safety profile superior to methadone, and possesses analgesic properties. For outpatient use, buprenorphine is combined with naloxone (BUP/NLX) to reduce the potential for abuse (i.e., IV administration). When given to those who abuse prescription opioids BUP/NLX possesses better treatment outcomes than those who abuse heroin. In one uncontrolled case series of 95 participants, Malinoff and his colleagues concluded that the effectiveness in the treatment of opioid dependence, in providing analgesia, and the low abuse liability make BUP/NLX a potentially useful treatment for patients with chronic pain and co-occurring opioid addiction. In a randomized controlled trial by Blondell et al. (2010), treatment with BUP/NLX was superior to the abstinence-oriented approach in regards to treatment retention in patients with chronic pain and co-existent opioid addiction. However, there has not been a randomized clinical trial comparing BUP/NLX with methadone maintenance in chronic pain patients with opioid addiction. Preliminary data suggest that both 6-months BUP/NLX and methadone treatment results analgesia, but methadone treatment results in better addiction outcomes. The present study is designed to determine the complexity of recovery outcomes (e.g., functioning, mental health) in chronic pain patients. Clinicians need evidence-based guidelines to more effectively manage patients who have both chronic pain and evidence of opioid misuse or addiction behaviors.

In this study, we plan to investigate whether patients treated with BUP/NLX and usual care will have improved clinical outcomes as those provided with methadone treatment and usual care. Specifically, we propose to give 63 patients BUP/NLX therapy for 6 months (experimental group) and 63 patients methadone therapy over 6 (active comparator). We hypothesize that patients given BUP/NLX treatment will have similar outcomes as those receiving methadone maintenance with respect to functioning, mental health, pain level, and treatment retention.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Trial Comparing Buprenorphine and Methadone for Treatment in Opioid Dependent Chronic Back Pain Patients
• Study Start Date: February 2012
• Actual Primary Completion Date: May 2014
• Actual Study Completion Date: May 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Methadone; 10-60 mg/day divided by 2-4 times a day	Drug: Methadone; 10-60 mg/day divided by 2-4 times a day for 6 months; Other Name: Dolophine
Experimental: Buprenorphine/naloxone; 4-16 mg/day divided by 2-4 times a day	Drug: Buprenorphine/naloxone; 4-16 mg/day divided by 2-4 times a day for 6 months; Other Name: Suboxone

Outcome Measures

Primary Outcome Measures :

1. Analgesia [ Time Frame: 6 months ]
   Pain severity will be measured using the Visual Analogue Scale (VAS) which has a range of 0-100 with 0 being no pain and 100 being worse possible pain.

Secondary Outcome Measures :

1. Illicit Drug Use [ Time Frame: 6 months ]
   Illicit opioid use will be measured by self-report and confirmed with urine toxicology.
2. Cravings [ Time Frame: at 6 months ]
   Cravings will be assessed using the Visual Analogue Scale (VAS) with 0 being no cravings and 100 being worse possible cravings
3. Functioning [ Time Frame: at 6 months ]
   Functioning will be assessed using the Visual Analogue Scale (VAS) with 0 being "no limits" and 100 being "bedridden."
4. Depression [ Time Frame: at 6 months ]
   Depression will be assessed using the Beck Depression Inventory, a 63 point scale with 0 being "none" and 63 being "severe."
5. Treatment Retention [ Time Frame: 6 months ]
   Number of participants that completed the study protocol

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. have a well-documented chronic pain disorder due to past back surgery,
2. have a chronic back pain syndrome,
3. have evidence of opioid addiction,
4. prior attempt at abstinence-oriented treatment documented by the referring physician,
5. be able to understand spoken and written English,
6. reside in Erie or Niagara counties,
7. have health insurance or other ability to pay for treatment with the approval from patient's primary physician;
8. have no prior history of methadone or BUP/NLX maintenance treatment since the last surgery,
9. not be a member of a vulnerable population, including prisoners

Exclusion Criteria:

1. homeless, or any patient without a "locator" (no means to participate in the follow-up data collection interviews by phone),
2. inability to give consent,
3. those with major co-occurring psychiatric disorders,
4. EKG showing prolonged QT and/or previous cardiac issues,
5. are taking a medication that is contraindicated with methadone,
6. medically unstable,
7. urine positive for cocaine at initial visit,
8. pregnant women

Contacts and Locations

Locations

United States, New York

UB/MD Family Medicine, Inc.

Amherst, New York, United States, 14228

Sponsors and Collaborators

State University of New York at Buffalo

Investigators

• Study Director: Rachel A Rizzo, MPH; University at Buffalo

More Information

Publications:

Neumann AM, Blondell RD, Jaanimägi U, Giambrone AK, Homish GG, Lozano JR, Kowalik U, Azadfard M. A preliminary study comparing methadone and buprenorphine in patients with chronic pain and coexistent opioid addiction. J Addict Dis. 2013;32(1):68-78. doi: 10.1080/10550887.2012.759872.

• Responsible Party: State University of New York at Buffalo
• ClinicalTrials.gov Identifier: NCT01559454
• Other Study ID Numbers: FMD0600908A
• First Posted: March 21, 2012
• Results First Posted: February 20, 2017
• Last Update Posted: February 20, 2017
• Last Verified: January 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: We are preparing a de-identified data set that could be shared.

Keywords provided by State University of New York at Buffalo:

chronic pain; opioid dependence; methadone; buprenorphine; substance use disorder

Additional relevant MeSH terms:

Back Pain; Low Back Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Analgesics, Opioid; Buprenorphine; Methadone; Buprenorphine, Naloxone Drug Combination; Naloxone; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Narcotic Antagonists; Antitussive Agents; Respiratory System Agents