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

Primary Purpose

Chronic Low Back Pain, Degenerative Disc Disease, Depression

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Oxycodone
Morphine
Placebo
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Low Back Pain focused on measuring low back pain, opioids, mood symptoms

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Low Negative Affect (NA)

Moderate NA

High NA

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
December 28, 2011
Last Updated
June 14, 2017
Sponsor
Brigham and Women's Hospital
Collaborators
Arthritis Foundation, National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT01502644
Brief Title
Opioid Treatment for Chronic Low Back Pain and the Impact of Mood Symptoms
Official Title
Opioid Treatment for Chronic Low Back Pain and the Impact of Mood Symptoms
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
February 2009 (Actual)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
Arthritis Foundation, National Institute on Drug Abuse (NIDA)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Low Back Pain, Degenerative Disc Disease, Depression, Anxiety
Keywords
low back pain, opioids, mood symptoms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
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.
Allocation
Non-Randomized
Enrollment
81 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low Negative Affect (NA)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Moderate NA
Arm Type
Active Comparator
Arm Description
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.
Arm Title
High NA
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Oxycodone
Intervention Description
Daily dosage up to 120 mg
Intervention Type
Drug
Intervention Name(s)
Morphine
Other Intervention Name(s)
Morphine sulfate (MS) Contin, Morphine sulfate instant release (MSIR), Morphine sulfate extended release (MSER)
Intervention Description
Daily dosage up to 90 mg immediate release or 180 mg extended release
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo-matching oxycodone, placebo-matching morphine
Primary Outcome Measure Information:
Title
Percent Change in Average Daily Pain Score
Description
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.
Time Frame
Baseline and Week 20

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajay D Wasan, MD, MSc
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Chestnut Hill
State/Province
Massachusetts
ZIP/Postal Code
02467
Country
United States

12. IPD Sharing Statement

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

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