Opioid Treatment for Chronic Low Back Pain and the Impact of Mood Symptoms
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Percent Change in Average Daily Pain Score
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
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.
入排标准
- 年龄范围
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Oxycodone (Drug)
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.
干预措施: Morphine (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Oxycodone (Drug)
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.
干预措施: Morphine (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Oxycodone (Drug)
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.
干预措施: Morphine (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change in Average Daily Pain Score
时间窗: Baseline and Week 20
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.
次要结局
未报告次要终点
研究者
Ajay D. Wasan,M.D.,M.Sc.
Assistant Professor of Anesthesiology and Psychiatry
Brigham and Women's Hospital