N/A N=27 Randomized Double-blind Basic Science

The Effects of Minocycline in Opioid-maintained Patients

Opioid Dependence · Pain

Bottom Line

View on ClinicalTrials.gov: NCT02359006 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Jan 2019

Primary outcome: Primary: Pain Threshold — 18.72; 24.78; 16.16; 24.37 seconds

Study Design & Population

Study type: Interventional
Phase: N/A
Interventions: Minocycline (Drug); Placebo (Drug)
Age: Adult · 18+ yrs
Sex: All
Sponsor: Yale University
Primary completion: Apr 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY Pain Threshold	18.72; 24.78; 16.16; 24.37; 16.13; 18.46	—
PRIMARY Pain Tolerance	40.86; 59.72; 37.42; 52.56; 34.41; 48.42	—
SECONDARY Brief Pain Inventory - Short Form: Pain Severity	1.28; 1.10; 0.88; 0.95; 0.78; 1.00	—
SECONDARY Brief Pain Inventory - Short Form: Interference	0.93; 0.97; 0.90; 1.33; 0.63; 1.04	—
SECONDARY Opioid Withdrawal Symptom Checklist (OWSC): Back Pain Item	0; 0.10; 0; 0.10; 0.10; 0.20	—
SECONDARY Profile of Mood States (POMS) Depression Subscale	20.80; 18.9; 18.9; 17.9; 21.00; 16.7	—
SECONDARY Profile of Mood States (POMS) - Total Mood Disturbance	43.1; 47.4; 44.7; 41.88; 50.3; 40.4	—
SECONDARY Short-Form McGill Pain Questionnaire (SF-MPQ): Sensory Subscale	10.33; 12.9; 10.9; 13.1; 10.8; 14.2	—
SECONDARY Short-Form McGill Pain Questionnaire (SF-MPQ): Affective Subscale	2.0; 1.5; 1.7; 1.7; 1.9; 2.2	—
SECONDARY Interleukin-1 Beta (IL-1β)	0.80; 0.72; 0.67; 0.62	—
SECONDARY Interleukin-6 (IL-6)	1.64; 1.11; 2.14; 1.99	—
SECONDARY Tumor Necrosis Factor Alpha (TNF-α)	2.86; 2.66; 2.66; 2.53	—
SECONDARY Ecological Momentary Assessments (EMA) - Pain	1.22; 1.14	—
SECONDARY Ecological Momentary Assessments (EMA) - Craving	1.04; 1.14	—
SECONDARY Ecological Momentary Assessments (EMA): SOWS	1.05; 1.03	—
SECONDARY Digit Symbol Substitution Test	37.11; 37.11; 42.33; 40.89; 41.78; 40.89	—
SECONDARY Sustained Attention to Response Test (SART): No-go Trials: Errors of Commission	7; 9; 5.78; 8.33; 5.75; 7.33	—
SECONDARY Sustained Attention to Response Test (SART): Go Trials: Errors of Omission	10.9; 17.9; 9.11; 13.78; 6.88; 13.44	—

Summary

Opioids are the most commonly utilized pharmacological treatment for moderate to severe pain. However, their clinical value is hindered by the development of opioid-induced hyperalgesia (OIH). OIH manifests as heightened pain sensitivity, and is an increasingly challenging drawback to the efficacy of opioid treatment. Although the mechanism of action modulating OIH is not completely understood, previous animal studies suggest that this phenomenon is a result of proinflammatory responses. Thus, administering an adjunct anti-inflammatory agent may attenuate OIH. Minocycline is one such agent; it is a tetracycline derivative antibiotic that inhibits microglia activation, nitric oxide (NO) production, and the release of pro-inflammatory cytokines and chemokines. In fact, recent evidence suggests that minocycline may attenuate the neuroinflammatory effects of opioids while enhancing their antinociceptive effects. Therefore, the investigators will determine if minocycline will mitigate OIH in methadone-maintained patients.

Eligibility Criteria

Inclusion Criteria

Males and females, between the ages of 18 and 55
Diagnosed with opioid dependence and currently enrolled in methadone maintenance treatment
Compliant in methadone maintenance treatment and on a stable dose for two weeks or greater
No current dependence or abuse of any other drugs (other than tobacco or marijuana)
No current medical problems
For women:
not pregnant as determined by pregnancy screening;
not breast feeding; u
using acceptable birth control methods;
not experiencing moderate to severe premenstrual symptoms (may interfere with pain assessment);
regular menstrual cycles

Exclusion Criteria

Current major psychiatric illnesses including mood, psychotic, or anxiety disorders
History of major medical illnesses, including liver diseases, heart disease, or other medical conditions that the physician investigator deems contraindicated for inclusion in the study
Current use of over-the-counter or prescription psychoactive drugs (including regular use of NSAIDS, antidepressant, anxiolytics, antipsychotics, mood stabilizers, psychostimulants) or drugs that would be expected to have major interactions with drugs to be tested, e.g., benzodiazepines, codeine, Percocet, and other opiate drugs
Liver function tests (ALT or AST) greater than 3x normal
Allergy to minocycline or other tetracyclines

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02359006). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.