Reduced Opioid Analgesic Requirements Via Improved Endogenous Opioid Function
NCT ID: NCT02469077
Last Updated: 2020-09-23
Study Results
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View full resultsBasic Information
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COMPLETED
NA
117 participants
INTERVENTIONAL
2015-08-31
2019-09-30
Brief Summary
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Detailed Description
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This project will determine whether enhancing endogenous opioids (via aerobic exercise training) permits achieving desired levels of analgesia with lower dosages of opioid analgesics, and fewer side effects and abuse-relevant drug effects. This 4 year project will test study hypotheses in a sample of 116 chronic low back pain patients. The study will have two key elements: 1) a randomized, controlled aerobic exercise manipulation in CP patients completing daily electronic pain diaries and 2) laboratory evoked thermal pain protocols pre- and post-exercise permitting direct examination of changes in both opioid analgesic effects (in response to a series of incremental morphine doses) and EO activity (indexed by comparing pain responses after placebo vs. opioid blockade).
The study will use a 6 week supervised aerobic exercise manipulation, with subjects randomly assigned to the exercise protocol or a no exercise control condition.
The study will employ a mixed between/within-subjects design using double-blind, counterbalanced, placebo-controlled administration of both an opioid antagonist (naloxone) and an opioid agonist (morphine). All participants will undergo three identical laboratory pain-induction sessions (each ≈5 days apart) prior to randomization to experimental condition, and again at the end of the 6 week exercise manipulation period (regardless of exercise group assignment) during which they will receive the 3 study drugs and participate in controlled laboratory evaluation of evoked thermal pain responsiveness.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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6 week aerobic exercise intervention
Participants randomly assigned to the exercise condition will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks). Immediately before and after participating in this intervention arm, participants will undergo laboratory evoked thermal pain response testing with placebo-controlled morphine and naloxone administration to assess mechanisms of exercise-related changes.
6 week aerobic exercise intervention
Participants randomly assigned to the 6 week aerobic exercise intervention will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks).
Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise will be progressively increased up to target during the first two weeks to avoid symptom exacerbation and minimize study drop-out.
Placebo
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
Morphine
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
naloxone
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
Normal exercise (control)
Participants assigned to the control condition will not undergo any exercise manipulation during this 6 week period, and will be asked to continue their current activity levels and not engage in any additional exercise activity during the study period. Immediately before and after participating in this intervention arm, participants will undergo laboratory evoked thermal pain response testing with placebo-controlled morphine and naloxone administration to assess mechanisms of exercise-related changes.
Placebo
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
Morphine
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
naloxone
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
Interventions
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6 week aerobic exercise intervention
Participants randomly assigned to the 6 week aerobic exercise intervention will complete an 18 session aerobic exercise manipulation supervised by an American College of Sports Medicine-certified personal trainer (3 exercise sessions per week for 6 weeks).
Each exercise session will consist of a 5 minute warm-up, 30 minutes of aerobic exercise, followed by a 5 minute cool-down period. Aerobic exercise will consist of treadmill walking/running, stepping, elliptical, or cycling exercise as preferred by the participant. Duration of exercise will be standardized at 30 minutes with a target exercise intensity between 70-85% Heart Rate Reserve (RPE = 15, hard). Because of the focus on de-conditioned individuals with Chronic Low Back Pain, the duration and intensity of exercise will be progressively increased up to target during the first two weeks to avoid symptom exacerbation and minimize study drop-out.
Placebo
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
Morphine
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
naloxone
In randomized order (crossover) across 3 laboratory sessions each approximately 5 days apart, participants will undergo laboratory evoked thermal pain response testing with: 1) 4 doses of saline placebo (20ml each), 2) an 8mg dose of naloxone (in 20ml saline vehicle), followed by saline, 4mg naloxone, and saline, or 3) morphine sulfate (0.03 mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02mg/kg each).
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Ability to read and write in English sufficiently to understand and complete study questionnaires
* Age 18-55 inclusive
* Presence of persistent daily low back pain of at least three months duration and of at least a 3/10 in average intensity
Exclusion Criteria
* History of renal or hepatic dysfunction
* Current or past alcohol or substance dependence
* A history of PTSD, psychotic, or bipolar disorders
* Chronic pain due to malignancy (e.g., cancer), autoimmune disorders (e.g., rheumatoid arthritis, lupus), or fibromyalgia
* Recent daily opiate use
* Use of any opioid analgesic medications within 72 hours of study participation (confirmed through rapid urine screening conducted prior to study participation)
* Females who are pregnant
* History of cardiovascular disease (including myocardial infarction)
* History of seizure disorder
* Prior allergic reaction/intolerance to morphine or its analogs
* Presence of cardiac disease or any other medical condition that would make engaging in the aerobic exercise manipulation unsafe
18 Years
55 Years
ALL
No
Sponsors
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National Institute on Drug Abuse (NIDA)
NIH
Vanderbilt University Medical Center
OTHER
Responsible Party
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Stephen Bruehl, PhD
Professor of Anesthesiology
Principal Investigators
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Stephen Bruehl, PhD
Role: PRINCIPAL_INVESTIGATOR
Vanderbilt University Medical Center
Locations
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Rush University
Chicago, Illinois, United States
Vanderbilt University
Nashville, Tennessee, United States
Countries
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References
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Provided Documents
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Document Type: Informed Consent Form
Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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141862
Identifier Type: -
Identifier Source: org_study_id
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