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

NCT ID: NCT01502644

Last Updated: 2017-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2013-01-31

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.

Detailed Description

The level of high, moderate or low NA was determined based on the participant's score on the Hospital Anxiety and Depression Scale (HADS). The HADS is a self-reported questionnaire that has 14 questions related to 2 domains: Anxiety subscale (7 questions) and Depression subscale (7 questions). Each item on the questionnaire is scored from 0 (least amount of anxiety/depression) to 3 (greatest amount of anxiety/depression), with total score between 0 and 21 for either anxiety or depression. Participants were assigned to high, moderate or low NA groups using the following HADS score criteria:

• High NA = HADS score ≥9 on each subscale
• Moderate NA = HADS score ≥6 to ≤8 on each subscale
• Low NA = HADS score ≤5 on each subscale

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Low Negative Affect (NA)

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.

Group Type: ACTIVE_COMPARATOR

Oxycodone

Intervention Type: DRUG

Daily dosage up to 120 mg

Morphine

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Placebo-matching oxycodone, placebo-matching morphine

Moderate NA

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.

Group Type: ACTIVE_COMPARATOR

Oxycodone

Intervention Type: DRUG

Daily dosage up to 120 mg

Morphine

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Placebo-matching oxycodone, placebo-matching morphine

High NA

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.

Group Type: ACTIVE_COMPARATOR

Oxycodone

Intervention Type: DRUG

Daily dosage up to 120 mg

Morphine

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Placebo-matching oxycodone, placebo-matching morphine

Interventions

Oxycodone

Daily dosage up to 120 mg

Intervention Type: DRUG

Morphine

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

Intervention Type: DRUG

Placebo

Placebo-matching oxycodone, placebo-matching morphine

Intervention Type: DRUG

Other Intervention Names

Morphine sulfate (MS) Contin; Morphine sulfate instant release (MSIR); Morphine sulfate extended release (MSER)

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Arthritis Foundation

OTHER

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ajay D. Wasan,M.D.,M.Sc.

Assistant Professor of Anesthesiology and Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ajay D Wasan, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Chestnut Hill, Massachusetts, United States

Countries

United States

Other Identifiers

5K23DA020681-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2007P-001047

Identifier Type: -

Identifier Source: org_study_id