Mirtazapine to Reduce Methamphetamine Use Among MSM With High-risk HIV Behaviors

This study has been completed.
Sponsor:
Collaborators:
Public Health Foundation Enterprises, Inc.
Information provided by (Responsible Party):
Phillip Coffin, MD, MIA, San Francisco Department of Public Health
ClinicalTrials.gov Identifier:
NCT00497081
First received: July 5, 2007
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

Studies demonstrate that methamphetamine (meth) use is associated with high-risk sexual behavior among MSM, putting meth-using MSM at extraordinarily high risk for transmitting or acquiring HIV. This study of intermediate size (60 participants) and length (3 months of follow-up) will assess the efficacy of mirtazapine in reducing methamphetamine use among high-risk MSM.


Condition Intervention Phase
Substance Abuse
HIV Infections
Drug: mirtazapine
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mirtazapine to Reduce Methamphetamine Use Among MSM With High-risk HIV Behaviors

Resource links provided by NLM:


Further study details as provided by San Francisco Department of Public Health:

Primary Outcome Measures:
  • Change in Number of Positive Methamphetamine Urine Tests, Comparing Baseline (Week 0) to Final Visit (Week 12). [ Time Frame: Baseline (week 0) and Final Visit (week 12) ] [ Designated as safety issue: No ]
  • Proportion of Days With Recorded Pill Bottle Opening, as Determined by MEMS. [ Time Frame: Daily, from Baseline (week 0) through Final Visit (week 12) ] [ Designated as safety issue: No ]
    Proportion of days with recorded pill bottle opening, as determined by MEMS (medication event monitoring system).

  • Frequency of Adverse Events Reported [ Time Frame: From Baseline (week 0) through Final Visit (week 12) ] [ Designated as safety issue: Yes ]

Enrollment: 60
Study Start Date: May 2007
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Mirtazapine
mirtazapine 30 mg daily
Drug: mirtazapine
mirtazapine 30 mg daily for 3 months
Other Name: Remeron
Placebo Comparator: Placebo
placebo 30 mg daily
Drug: placebo
placebo 30 mg daily for 3 months

Detailed Description:

Methamphetamine use is especially prevalent among men who have sex with men (MSM). Population-based surveys report methamphetamine use rates 20 times higher among MSM compared with the general population. Methamphetamine use is also a driving force in the MSM HIV epidemic: methamphetamine use has been associated with increased number of sexual partners, unprotected sex acts, and sexually transmitted infection (STI) and HIV acquisition. Despite these alarming data, relatively few interventions have been tested among methamphetamine-using MSM, and no studies have tested the efficacy of pharmacologic interventions in reducing methamphetamine use in this population. In parallel with the continued testing of behavioral approaches, we believe the time has come to test pharmacologic interventions to reduce methamphetamine use among MSM. Pharmacologic approaches to treating substance use have been successful in treating nicotine, alcohol, and heroin dependence. No studies have tested a pharmacologic intervention to reduce methamphetamine use among MSM at high risk for HIV acquisition and transmission. A recent pilot study found that mirtazapine, a drug with dual dopaminergic and serotonergic properties, significantly reduced methamphetamine withdrawal symptoms when compared to placebo over a two-week period among Thai men in a drug probation center. Mirtazapine is a commonly used, FDA-approved antidepressant; however, in the Thai study its effects on methamphetamine withdrawal were independent of its effects on depressive symptoms, suggesting a direct effect of mirtazapine on treating methamphetamine dependence. We propose to expand upon these promising pilot results by conducting a study of intermediate size (60 participants) and length (3 months of follow-up) to assess the efficacy of mirtazapine in reducing methamphetamine use among high-risk MSM.

The specific aims of our study are:

  1. To test the hypothesis that mirtazapine 30 mg daily will reduce methamphetamine use significantly more than placebo among methamphetamine-dependent MSM, as determined by the proportion of methamphetamine-negative urines and by self-report of methamphetamine use in the mirtazapine versus placebo group.
  2. To measure the acceptability of mirtazapine and placebo among methamphetamine-dependent MSM, by determining (via electronic pill caps and self-report) medication adherence to mirtazapine and placebo.
  3. To measure the safety and tolerability of mirtazapine and placebo among methamphetamine-dependent MSM, as determined by the number of adverse clinical events in the mirtazapine and placebo arms.

If promising, study results will be used to design a phase III clinical trial to determine if mirtazapine's effects on reducing methamphetamine use lead to reductions in methamphetamine-associated sexual risk. We have chosen first to conduct a 3-year intermediate-sized trial in order to determine if mirtazapine reduces methamphetamine use and whether mirtazapine demonstrates good acceptability and tolerability among a population with methamphetamine-associated high-risk sexual behaviors. If this proves to be the case, we believe our study results will provide strong support for a much larger trial to test the hypothesis that mirtazapine-driven reductions in methamphetamine use will result in corresponding decreases in sexual risk behavior. This study is therefore designed to reflect the structure of a larger HIV-risk reduction trial and includes both substance use and sexual risk behavior measures. We will enroll sexually active, methamphetamine-dependent MSM (either HIV-negative or HIV-positive) who will be randomized 1:1 to receive mirtazapine or placebo for 90 days. Because no medications have been approved to treat methamphetamine dependence, we include extensive safety parameters, as is required by the Food and Drug Administration (FDA) when testing a medication for a new indication in a new population. Participants will be seen weekly for urine drug testing and for brief substance use counseling. All will receive HIV risk-reduction counseling. Behavior will be assessed using standardized measures via audio computer-assisted self-interview (ACASI).

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. HIV-negative by rapid test, or documentation of HIV infection with a laboratory result of a positive HIV test;
  2. male gender;
  3. reports having anal sex with men in the prior 3 months while using methamphetamine;
  4. diagnosed with methamphetamine dependence as determined by SCID;
  5. interested in stopping or reducing methamphetamine use;
  6. at least one methamphetamine-positive urine at screening and run-in period;
  7. no known allergies to mirtazapine;
  8. no current acute illnesses requiring prolonged medical care;
  9. no chronic illnesses that are likely to progress clinically during trial participation;
  10. able and willing to provide informed consent and to be followed over a 3-month period;
  11. age 18-60 years;
  12. baseline CBC, total protein, albumin, glucose, alk phos, creatinine, BUN and electrolytes without clinically significant abnormalities as determined by investigator in conjunction with symptoms, physical exam, and medical history.

Exclusion Criteria:

  1. evidence of current major depression, as determined by SCID;70
  2. history of bipolar disorder or psychosis, as determined by SCID;
  3. taking anti-depressant or other psychotropic medication within the last 30 days, including mirtazapine or a monoamine oxidase (MAO) inhibitor;
  4. currently using or unwilling not to use pseudoephedrine-containing products for trial duration (causes false positive urines for methamphetamine use);
  5. current CD4 count < 200 cells/mm3;
  6. measured moderate or severe liver disease (AST, ALT, and total bilirubin > 3 times upper limit of normal) and/or any symptoms of current liver disease;
  7. impaired renal function (creatinine clearance < 60 ml/min);
  8. currently participating in another research study;
  9. any condition that, in the principal investigator's judgment, interferes with safe study participation or adherence to study procedures.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00497081

Locations
United States, California
San Francisco Department of Public Health, AIDS Office
San Francisco, California, United States, 94102
Sponsors and Collaborators
San Francisco Department of Public Health
Public Health Foundation Enterprises, Inc.
Investigators
Principal Investigator: Grant N Colfax, MD Co-Directior, HIV Epidemiology Section, San Francisco Department of Public Health
  More Information

Publications:
Responsible Party: Phillip Coffin, MD, MIA, Principal Investigator, San Francisco Department of Public Health
ClinicalTrials.gov Identifier: NCT00497081     History of Changes
Other Study ID Numbers: 1 R01 DA022155-01, R01DA022155, 1R01DA022155-01, DPMC
Study First Received: July 5, 2007
Results First Received: October 7, 2014
Last Updated: October 15, 2014
Health Authority: United States: Federal Government

Keywords provided by San Francisco Department of Public Health:
Methamphetamine
HIV
MSM
HIV Seronegativity

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Methamphetamine
Mianserin
Mirtazapine
Adrenergic Agents
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Uptake Inhibitors
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents, Tricyclic
Autonomic Agents
Central Nervous System Agents
Central Nervous System Stimulants
Dopamine Agents
Dopamine Uptake Inhibitors
Histamine Agents
Histamine Antagonists
Histamine H1 Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 23, 2014