The Effects of Minocycline in Opioid-maintained Patients

NCT02359006 | Completed Results DMC

• 2 other identifiers: 14120151192T32DA007238-26
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Opioid Dependence; Pain

Keywords

Analgesia; pain analgesia; methadone; opiates

Outcome Measures

Primary Outcomes (2)

• Pain Threshold

  The Cold Pressor Test (CPT) measures pain threshold (in seconds). For this test, two water coolers filled with either warm (100.04ºF/37.8ºC) or cold water (32.9-34.7ºF/0.5-1.5ºC) are used. To begin the CPT, participants first immerse their hand into the warm-water bath for 2 min. Participants are then instructed to immerse their hand into the cold water bath and report the first time they experience pain (pain threshold). Lower scores indicate lower pain threshold. Minimum score is 0 seconds, and a maximum cut-off score of 300 seconds is used to prevent tissue damage.

  One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28)

• Pain Tolerance

  The Cold Pressor Test (CPT) measures pain threshold and pain tolerance (in seconds). For this test, two water coolers filled with either warm (100.04ºF/37.8ºC) or cold water (32.9-34.7ºF/0.5-1.5ºC) are used. To begin the CPT, participants first immerse their hand into the warm-water bath for 2 min. Participants are then instructed to immerse their hand into the cold water bath and report when the pain becomes unbearable (pain tolerance). Lower scores indicate lower pain tolerance. Minimum score is 0 seconds, and a maximum cut-off score of 300 seconds is used to prevent tissue damage.

  One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28)

Secondary Outcomes (16)

• Brief Pain Inventory - Short Form: Pain Severity

  One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28)

• Brief Pain Inventory - Short Form: Interference

  One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28)

• Opioid Withdrawal Symptom Checklist (OWSC): Back Pain Item

  One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28)

• Profile of Mood States (POMS) Depression Subscale

  One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28)

• Profile of Mood States (POMS) - Total Mood Disturbance

  One measurement at each of 5 weekly sessions: Baseline, Day 8, Day 15, Day 22 and at Follow-up (~Day 28)

Study Arms (2)

minocycline

ACTIVE COMPARATOR

200mg minocycline

Drug: Minocycline

Placebo

PLACEBO COMPARATOR

Sugar pill

Drug: Placebo

Interventions

Minocycline DRUG

Minocycline will be compared with placebo

Also known as: tetracycline

minocycline

Placebo DRUG

Placebo will be compared with minocycline

Also known as: sugar pill

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Current major psychiatric illnesses including mood, psychotic, or anxiety disorders
• 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

Sponsors & Collaborators

• Yale University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

VA Hospital

West Haven, Connecticut, 06516, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders; Pain; Agnosia

Interventions

Minocycline; Tetracycline; Sugars

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Carbohydrates

Results Point of Contact

• Title: Dr. Mehmet Sofuoglu
• Organization: Yale University

mehmet.sofuoglu@yale.edu

203-932-5711

Study Officials

• Mehmet Sofuoglu, M.D., Ph.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2015
• First Posted: February 9, 2015
• Study Start: March 12, 2015
• Primary Completion: April 19, 2017
• Study Completion: April 19, 2017
• Last Updated: March 6, 2020
• Results First Posted: January 9, 2019

Record last verified: 2020-03

Locations

US (1)