Clinical trial NCT02469077: Reduced Opioid Analgesic Requirements Via Improved Endogenous Opioid Function
Official title: Reduced Opioid Analgesic Requirements Via Improved Endogenous Opioid Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Pain
Keywords: Chronic Low Back Pain
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2015-06-11
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Chronic Pain (CP) management has increasingly utilized long-term opioid analgesic therapy, a change associated with increased opioid abuse (via greater exposure in vulnerable individuals), non-pain health consequences (hormone changes, falls), and a dramatic rise in opioid-related overdoses and deaths. Treatment strategies that minimize the need for chronic high-dose opioids are sorely needed. This project will test the novel hypothesis that effective pain relief can be achieved at lower opioid analgesic doses by increasing levels of endogenous opioids (EOs).

Detailed description: There are three separate goals of the study: 1) test the effects of the intervention (versus control) on clinical outcomes, 2) test for endogenous opioid mechanisms of the intervention (indexed by the difference in laboratory evoked pain response between placebo and naloxone drug conditions), and 3) test the effects of the intervention on morphine responses (indexed by the difference in evoked pain response between placebo and morphine laboratory drug conditions).

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.

Eligibility criteria: Inclusion Criteria:

* Intact cognitive status and ability to provide informed consent
* 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:

* Engagement in \> 2 days/wk and \> 60 min/wk of moderate or vigorous intensity activity based on responses to 6 validated survey questions at screening (CDC BRFSS)
* 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

Primary outcomes:
measure: Mean of the Change in Morphine Dosage (in mg) Required to Achieve 25% Reduction in Thermal Evoked Pain Responses Relative to Baseline (Pre-intervention) Placebo Condition Responses
timeFrame: At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)
measure: Mean Change in 5-day Electronic Diary Ratings of Low Back Pain Intensity
timeFrame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
Secondary outcomes:
measure: Mean Change in Placebo Condition Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form
timeFrame: At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)
measure: Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form
timeFrame: At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)
measure: Mean Change in McGill Pain Questionnaire-2 Total Chronic Back Pain Ratings
timeFrame: At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)
measure: Mean Within-participant Changes From Pre- to Post-intervention in Opioid Blockade Effects (Within-participant Difference Between Naloxone and Placebo Conditions) for McGill Pain Questionnaire-2 Total Ratings of Back Pain.
timeFrame: At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)
measure: Mean Change in Positive and Negative Affect Scale-Negative Affect Subscale Ratings.
timeFrame: At pre intervention baseline and again post-intervention (an expected average of 6 weeks later)
measure: Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Euphoria Subscale Ratings
timeFrame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
measure: Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects Scale-Sedation Subscale Ratings
timeFrame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
measure: Mean Change in Morphine Condition Visual Analog Scale (VAS) Opioid Effects - Unpleasantness Subscale Ratings
timeFrame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
measure: Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Effect Subscale Ratings
timeFrame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
measure: Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Drug Liking Subscale Ratings
timeFrame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
measure: Mean Change in Morphine Condition Drug Effects, Liking, and Take Again (DELTA) -Take Again Subscale Ratings
timeFrame: At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Stephen Bruehl, PhD
role: PRINCIPAL_INVESTIGATOR
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