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

Tracking Information
First Submitted Date ICMJE	July 5, 2007
First Posted Date ICMJE	July 6, 2007
Results First Submitted Date	October 7, 2014
Results First Posted Date	October 20, 2014
Last Update Posted Date	January 5, 2015
Study Start Date ICMJE	May 2007
Actual Primary Completion Date	March 2010 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: October 15, 2014)	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) ]; Proportion of Days With Recorded Pill Bottle Opening, as Determined by MEMS. [ Time Frame: Daily, from Baseline (week 0) through Final Visit (week 12) ]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) ]
Original Primary Outcome Measures ICMJE; (submitted: July 5, 2007)	Feasibility: Proportion of persons screened who are eligible and enrolled; proportion of scheduled study visits completed and urine samples collected; final retention by study arm; Tolerability: Comparison of adverse events in the aripiprazole and placebo arms; Acceptability: Adherence to daily mirtazapine and placebo, as determined by MEMs and self-report, and proportion of participants discontinuing medication in both arms
Change History	Complete list of historical versions of study NCT00497081 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Mirtazapine to Reduce Methamphetamine Use Among MSM With High-risk HIV Behaviors
Official Title ICMJE	Mirtazapine to Reduce Methamphetamine Use Among MSM With High-risk HIV Behaviors
Brief Summary	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.
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: 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.; 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.; 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).
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Substance Abuse; HIV Infections
Intervention ICMJE	Drug: mirtazapine mirtazapine 30 mg daily for 3 months Other Name: Remeron; Drug: placebo placebo 30 mg daily for 3 months
Study Arms	Active Comparator: Mirtazapine mirtazapine 30 mg daily Intervention: Drug: mirtazapine; Placebo Comparator: Placebo placebo 30 mg daily Intervention: Drug: placebo
Publications *	Colfax GN, Santos GM, Das M, Santos DM, Matheson T, Gasper J, Shoptaw S, Vittinghoff E. Mirtazapine to reduce methamphetamine use: a randomized controlled trial. Arch Gen Psychiatry. 2011 Nov;68(11):1168-75. doi: 10.1001/archgenpsychiatry.2011.124.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 5, 2007)	60
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	March 2010
Actual Primary Completion Date	March 2010 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: HIV-negative by rapid test, or documentation of HIV infection with a laboratory result of a positive HIV test;; male gender;; reports having anal sex with men in the prior 3 months while using methamphetamine;; diagnosed with methamphetamine dependence as determined by SCID;; interested in stopping or reducing methamphetamine use;; at least one methamphetamine-positive urine at screening and run-in period;; no known allergies to mirtazapine;; no current acute illnesses requiring prolonged medical care;; no chronic illnesses that are likely to progress clinically during trial participation;; able and willing to provide informed consent and to be followed over a 3-month period;; age 18-60 years;; 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: evidence of current major depression, as determined by SCID;70; history of bipolar disorder or psychosis, as determined by SCID;; taking anti-depressant or other psychotropic medication within the last 30 days, including mirtazapine or a monoamine oxidase (MAO) inhibitor;; currently using or unwilling not to use pseudoephedrine-containing products for trial duration (causes false positive urines for methamphetamine use);; current CD4 count < 200 cells/mm3;; 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;; impaired renal function (creatinine clearance < 60 ml/min);; currently participating in another research study;; any condition that, in the principal investigator's judgment, interferes with safe study participation or adherence to study procedures.
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years to 60 Years (Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00497081
Other Study ID Numbers ICMJE	1R01DA022155-01( U.S. NIH Grant/Contract ); R01DA022155 ( U.S. NIH Grant/Contract ); 1R01DA022155-01 ( U.S. NIH Grant/Contract ); DPMC ( Other Identifier: NIDA )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Phillip Coffin, MD, MIA, San Francisco Department of Public Health
Study Sponsor ICMJE	San Francisco Department of Public Health
Collaborators ICMJE	National Institute on Drug Abuse (NIDA); Public Health Foundation Enterprises, Inc.
Investigators ICMJE	Principal Investigator: Grant N Colfax, MD Co-Directior, HIV Epidemiology Section, San Francisco Department of Public Health
PRS Account	San Francisco Department of Public Health
Verification Date	December 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP