Vanderbilt Clinical Trials

Reduced Opioid Analgesic Requirements Via Improved Endogenous Opioid Function

Purpose

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).

Condition

Chronic Pain

Eligibility

Eligible Ages: Between 18 Years and 55 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

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

Study Design

Phase: N/A
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: Double (Participant, Investigator)

Arm Groups

Arm	Description	Assigned Intervention
Experimental 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.	Behavioral: 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. Drug: 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). Other names: normal saline placebo Drug: 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). Other names: Astramorph Drug: 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 names: narcan
Active Comparator 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.	Drug: 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). Other names: normal saline placebo Drug: 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). Other names: Astramorph Drug: 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 names: narcan

More Details

Status: Completed
Sponsor: Vanderbilt University Medical Center

Study Contact

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.