Opioid Treatment for Chronic Low Back Pain and the Impact of Mood Symptoms

NCT01502644 | Completed Phase 4 Results DMC

• 2 other identifiers: 2007P-0010475K23DA020681-05
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

Opioids are frequently prescribed for chronic low back pain (CLBP). Psychiatric illness, such as high levels of depression and anxiety symptoms, is a common co-occurrence in chronic pain patients (and is termed comorbid negative affect \[NA\]). The purpose of the study is to determine whether CLBP patients with either a high vs. a low or moderate degree of NA have different pain relief responses to oral opioids.

Conditions

Chronic Low Back Pain; Degenerative Disc Disease; Depression; Anxiety

Keywords

low back pain; opioids; mood symptoms

Outcome Measures

Primary Outcomes (1)

• Percent Change in Average Daily Pain Score

  Participants rated their average lower back pain over the past 24 hours using an 11-point scale (0=no pain to 10=worst possible pain) and recorded it in an electronic diary. The percent change in pain score from baseline is calculated using weekly averages for up to 20 weeks. Linear mixed modeling (LMM) analysis was used to allow for inclusion in the analysis of the majority of participants with any missing data. For the LMM model, group, group × week, average baseline pain, and opioid use at baseline (yes/no) were entered as fixed effects using an autoregressive covariance structure. Participant, intercept, and week were entered as random effects, using a compound symmetry covariance structure. A positive change from baseline indicates an improvement.

  Baseline and Week 20

Study Arms (3)

Low Negative Affect (NA)

ACTIVE COMPARATOR

Participants with low NA (HADS score ≤5 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.

Drug: Oxycodone; Drug: Morphine; Drug: Placebo

Moderate NA

ACTIVE COMPARATOR

Participants with moderate NA (HADS score ≥6 to ≤8 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.

Drug: Oxycodone; Drug: Morphine; Drug: Placebo

High NA

ACTIVE COMPARATOR

Participants with high NA (HADS score ≥9 on each subscale) received placebo or active opioid drug (immediate-release morphine 15 to 30 mg or oxycodone 5 to 10 mg) up to three times a day as needed for 1 week each in random order, followed by morphine or oxycodone titrated to a maximum allowable daily dose in morphine equivalents of 30 mg for short-acting medication and 60 mg for long-acting medication, respectively, three times a day for up to 20 weeks, followed by morphine or oxycodone tapering (individualized opioid dose was decreased by approximately 25% each week) for 4 weeks.

Drug: Oxycodone; Drug: Morphine; Drug: Placebo

Interventions

Oxycodone DRUG

Daily dosage up to 120 mg

High NA; Low Negative Affect (NA); Moderate NA

Morphine DRUG

Daily dosage up to 90 mg immediate release or 180 mg extended release

Also known as: Morphine sulfate (MS) Contin, Morphine sulfate instant release (MSIR), Morphine sulfate extended release (MSER)

High NA; Low Negative Affect (NA); Moderate NA

Placebo DRUG

Placebo-matching oxycodone, placebo-matching morphine

High NA; Low Negative Affect (NA); Moderate NA

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Low Back Pain \> 3/10
• Pain \> 1 year
• Degenerative disc disease as seen on magnetic resonance imaging (MRI), which must meet minimum disc grading criteria: at least a grade III disc degeneration, a hyperintense zone, or abnormal disc morphology.
• Patients who may have had back surgery will be included.
• No epidural steroids or other nerve blocks for back pain either two weeks before or during the study period.
• No opioids or on short-acting opioids only (max. daily amount=120 mg morphine equivalents). It is not feasible to recruit only opioid naive patients.
• Must agree to 2-week washout for those on opioids.
• No active substance abuse.
• No intention to take new pain or psychiatric treatments during the study, including chiropractic, physical therapy, or complementary or alternative treatments (CAM). It is not feasible to take participants off of any other pain medications, such as nonsteroidal anti-inflammatory drugs (NSAIDS).
• No pregnancy or the intent to become pregnant during the study, and no nursing mothers.
• Women, who are able to bear children, must agree to use contraceptives throughout the study.
• In men, normal baseline testosterone levels.

You may not qualify if:

• Patients with pain due to disorders not including a component of disc degeneration, or those with unknown causes of pain will be excluded.
• Patients with the intent to undergo back surgery will be excluded.
• Patients with a history of recent or ongoing alcohol or other drug addiction disorders will be excluded.
• Patients with any history of substance abuse of opioids will be excluded.
• Patients whose diagnosis cannot be firmly established according to criteria described above would not be included.
• Patients whose medical and psychiatric comorbidities are not well controlled, or who are currently experiencing an acute exacerbation of the medical comorbidity, will be excluded.
• Males with abnormal testosterone levels will be excluded (normal range is 1800-6650 pg/ml).
• Female patients who nursing will be excluded.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Arthritis Foundation: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Brigham and Women's Hospital

Chestnut Hill, Massachusetts, 02467, United States

Location

MeSH Terms

Conditions

Intervertebral Disc Degeneration; Depression; Anxiety Disorders; Low Back Pain

Interventions

Oxycodone; Morphine

Condition Hierarchy (Ancestors)

Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Behavioral Symptoms; Behavior; Mental Disorders; Back Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Ajay D. Wasan, M.D., M.Sc.
• Organization: Brigham and Women's Hospital

awasan@partners.org

Study Officials

• Ajay D Wasan, MD, MSc

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: During the first 2 weeks of treatment participants took short-acting morphine or oxycodone for 1 week and placebo for 1 week in random order. Participants and investigators were blinded during this period. The remainder of the study was conducted in an open-label design.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anesthesiology and Psychiatry

Study Record Dates

• First Submitted: December 28, 2011
• First Posted: January 2, 2012
• Study Start: February 1, 2009
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: July 11, 2017
• Results First Posted: June 8, 2017

Record last verified: 2017-06

Locations

US (1)