Mirtazapine for the Treatment of Methamphetamine Dependence Among MSM (M2.0)

Mirtazapine for the Treatment of Methamphetamine Dependence Among MSM: a 6-month Randomized Controlled Trial With 3 Months of Follow-up

The investigators recently conducted a double-blind, randomized controlled trial (n=60) of limited duration (12 weeks), and found that compared with placebo, oral mirtazapine, an FDA-approved antidepressant, significantly reduced meth use in those receiving mirtazapine, as determined by reduction in meth-positive urines. Sexual risk behaviors also declined significantly in the mirtazapine arm compared to placebo. Mirtazapine decreased meth use despite low adherence: by medical event monitoring system (MEMS) caps, only 48.5% of daily doses were taken. All participants received weekly substance use counseling and monthly, brief clinician-delivered adherence counseling. The investigators propose expanding upon these results by lengthening the treatment period to 24 weeks, with adherence reminders added to the counseling, and determining if efficacy is sustained up to 12 weeks after drug discontinuation. The sample size for this 9-month study is 120.

Study Overview

• Status: Completed
• Conditions: Amphetamine-Related Disorders
• Intervention / Treatment: Drug: Placebo; Drug: Mirtazapine

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94102
      • Substance Use Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. born male, or born female and does not identify as female;
2. reports anal sex with men in the prior three months while under the influence of meth;
3. diagnosed with meth dependence by SCID;
4. interested in stopping or reducing meth use;
5. at least one meth-positive urine during screening and run-in period;
6. no current acute illness requiring prolonged medical care;
7. no serious chronic illnesses that are likely to progress clinically during trial participation;
8. able and willing to provide informed consent and adhere to visit schedule;
9. age 18-69 years;
10. baseline CBC, total protein, albumin, glucose, alkaline phosphatase, creatinine, BUN, and electrolytes without clinically significant abnormalities as determined by clinician in conjunction with symptoms, physical exam, and medical history
11. current CD4 count ≥ 200 cells/mm3; or CD4 count of 100 - 199 cells/mm3 and HIV viral load < 200 copies/mL
12. text-capable cell phone or access to email

Exclusion Criteria:

1. Evidence of current major depression by SCID;
2. history of bipolar disorder or psychotic disorder, as determined by SCID;
3. known allergy or previous adverse reaction to mirtazapine;
4. taking an anti-depressant medication within the past 30 days, including mirtazapine or a monoamineoxidase inhibitor;
5. moderate or severe liver disease (AST, ALT, and total bilirubin >= 5 times upper limit of normal);
6. impaired renal function (estimated GFR <40 ml/min);
7. currently participating in another research study;
8. pending legal proceedings with high risk for incarceration during the time of planned study participation;
9. any condition that, in the principal investigator's judgment, interferes with safe study participation or adherence to study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Mirtazapine; mirtazapine 30 mg orally per day	Drug: Mirtazapine; Other Names: Remeron
PLACEBO_COMPARATOR: Placebo; placebo (30 mg) orally per day	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of methamphetamine-positive urine tests	To determine the efficacy of mirtazapine vs placebo at 12 weeks and 24 weeks of treatment plus counseling, and to determine whether efficacy is sustained for an additional 12 weeks after discontinuation of treatment and counseling (weeks 24 to 36).	weekly for 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sexual risk (see description)	To assess if the intervention reduces HIV risk behaviors, including number of male sex partners, number of male anal sex partners with whom meth is used and episodes of unprotected anal sex with serodiscordant partners.	9 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to study drug	To measure the acceptability of mirtazapine and placebo by determining (via electronic pill boxes and self-report) medication adherence including percent of doses taken, taking less than 80% of medication, patterns of non-adherence (e.g. use every other day, during the weekend, longer alternating periods on and off medication), and time to stopping medication.	6 months
Number of adverse events	To measure the tolerability of mirtazapine and placebo, as determined by the number of adverse clinical events in the mirtazapine and placebo arms.	6 months

Collaborators and Investigators

• Sponsor: Phillip Coffin, MD, MIA
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Steven L Batki, M.D., University of California, San Francisco; Study Director: Emily Behar, San Francisco Department of Public Health

Publications and helpful links

General Publications

• Coffin PO, Santos GM, Hern J, Vittinghoff E, Walker JE, Matheson T, Santos D, Colfax G, Batki SL. Effects of Mirtazapine for Methamphetamine Use Disorder Among Cisgender Men and Transgender Women Who Have Sex With Men: A Placebo-Controlled Randomized Clinical Trial. JAMA Psychiatry. 2020 Mar 1;77(3):246-255. doi: 10.1001/jamapsychiatry.2019.3655.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): October 1, 2017
• Study Completion (ACTUAL): October 1, 2017

Study Registration Dates

• First Submitted: June 25, 2013
• First Submitted That Met QC Criteria: June 27, 2013
• First Posted (ESTIMATE): June 28, 2013

Study Record Updates

• Last Update Posted (ACTUAL): March 13, 2018
• Last Update Submitted That Met QC Criteria: March 9, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: HIV; sexual behavior
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Amphetamine-Related Disorders; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Adrenergic alpha-Antagonists; Adrenergic alpha-2 Receptor Antagonists; Mirtazapine
• Other Study ID Numbers: 1R01DA034527 (NIH); R01DA034527 (NIH)