The Effects of Minocycline in Opioid-maintained Patients

NCT ID: NCT02359006

Last Updated: 2020-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-12
• Study Completion Date: 2017-04-19

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.

Detailed Description

Sixty completers will be recruited through the VA methadone clinic, as well as through the APT Foundation Methadone Maintenance Program. After the initial phone screening, potential subjects will undergo a comprehensive evaluation which will include medical, psychiatric, and drug use histories as well as physical, psychiatric, and laboratory examinations. Laboratory examination will include CBC, liver and thyroid function tests, serum electrolytes, BUN, creatinine, PT, PTT, urine analysis (including urine pregnancy for women) and urine toxicology screening.

Participants will be terminated from the study following opioid relapse, or use of any other psychotropic medications. If participants are noncompliant (no-show, positive urine screening, noncompliance with medication protocol/missing more than one dose of minocycline/placebo), participation will be terminated.

This double-blind, randomized clinical trial will randomize male and female veterans and non-veterans currently undergoing methadone maintenance treatment for opioid dependence to either minocycline (200mg/day) or placebo for 15 days. Upon inclusion, participants will be subjected to a pain assessment to evaluate baseline pain thresholds and tolerance: the Cold Pressor Test. An experimental treatment of either minocycline or placebo will then be initiated and maintained for 15 days. Additionally, at the beginning of Week 2 of treatment, participants will be given a Personal Digital Assistant (PDA) an HP iPAQ Pocket PC 2003 Pro that will administer Ecological Momentary Assessments (EMA). Using EMA, we can assess change in pain sensitivity, withdrawal symptoms and cognitive performance in the participants' natural environment, which increases the ecological validity of the study. Participants will be asked to return to the laboratory several times a week for the 15 consecutive days that they are taking minocycline in order to receive the study medication and to assess changes in pain thresholds and tolerance (i.e. to assess the presence, or lack thereof of hyperalgesia). Upon completion of experimental treatment, participants will be asked to return a final time to undergo pain measurement once more, to assess any changes in pain sensitivity after completion of minocycline.

Conditions

Opioid Dependence; Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

minocycline

200mg minocycline

Group Type: ACTIVE_COMPARATOR

Minocycline

Intervention Type: DRUG

Minocycline will be compared with placebo

Placebo

Sugar pill

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be compared with minocycline

Interventions

Minocycline

Minocycline will be compared with placebo

Intervention Type: DRUG

Placebo

Placebo will be compared with minocycline

Intervention Type: DRUG

Other Intervention Names

tetracycline; sugar pill

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mehmet Sofuoglu, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

VA Hospital

West Haven, Connecticut, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2T32DA007238-26

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1412015119

Identifier Type: -

Identifier Source: org_study_id