Reduced Opioid Analgesic Requirements Via Improved Endogenous Opioid Function

NCT02469077 | Completed Results

• 2 other identifiers: 141862R01DA037891
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 2

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).

Conditions

Chronic Pain

Keywords

Chronic Low Back Pain

Outcome Measures

Primary Outcomes (2)

• 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

  At a laboratory testing day pre and post intervention each participant received morphine sulphate (0.3mg/kg in 20ml saline vehicle initially, followed by 3 incremental doses of 0.02 mg/kg each with testing for thermal evoked pain response. Weight adjusted dosing was used by multiplying the weight of each patient in kg by 0.3mg (dose 1 only) or by .02mg (doses 2-4), with all doses infused in 20mL saline vehicle. Mean of the change in morphine dosage required to achieve 25 % reduction in thermal evoked pain responses on testing day at baseline (pre-intervention) and post intervention. Positive values for the change in the mean between pre and post intervention indicated decreased morphine requirements post intervention.

  At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)

• Mean Change in 5-day Electronic Diary Ratings of Low Back Pain Intensity

  Mean change in 5-day electronic diary ratings of low back pain intensity from pre intervention baseline to post intervention. 9 point pain scale assessing pain intensity with 0 represents no pain and 8 represents worst possible pain. Positive values indicate reduced pain post intervention.

  At pre-intervention baseline and again post-intervention (an expected average of 6 weeks later)

Secondary Outcomes (11)

• Mean Change in Placebo Condition Ratings of Acute Thermal Pain Intensity on the McGill Pain Questionnaire-Short Form

  At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)

• 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

  At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)

• Mean Change in McGill Pain Questionnaire-2 Total Chronic Back Pain Ratings

  At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)

• 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.

  At pre-intervention baseline laboratory assessment and again post-intervention (an expected average of 6 weeks later)

• Mean Change in Positive and Negative Affect Scale-Negative Affect Subscale Ratings.

  At pre intervention baseline and again post-intervention (an expected average of 6 weeks later)

Study Arms (2)

6 week aerobic exercise intervention

EXPERIMENTAL

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; Drug: Placebo; Drug: Morphine; Drug: naloxone

Normal exercise (control)

ACTIVE COMPARATOR

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; Drug: Morphine; Drug: naloxone

Interventions

6 week aerobic exercise intervention BEHAVIORAL

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.

6 week aerobic exercise intervention

Placebo DRUG

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).

Also known as: normal saline placebo

6 week aerobic exercise intervention; Normal exercise (control)

Morphine DRUG

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).

Also known as: Astramorph

6 week aerobic exercise intervention; Normal exercise (control)

naloxone DRUG

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).

Also known as: narcan

6 week aerobic exercise intervention; Normal exercise (control)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (2)

Rush University

Chicago, Illinois, 60612, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

Related Publications (29)

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MeSH Terms

Conditions

Chronic Pain

Interventions

Morphine; Naloxone

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Stephen Bruehl, Ph.D.
• Organization: Vanderbilt University Medical Center

stephen.bruehl@vumc.org

615-936-1821

Study Officials

• Stephen Bruehl, PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Anesthesiology

Study Record Dates

• First Submitted: May 7, 2015
• First Posted: June 11, 2015
• Study Start: August 1, 2015
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: September 23, 2020
• Results First Posted: September 23, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)