Mirtazapine for the Treatment of Methamphetamine Use in Opioid Use Disorder Patients Receiving Medication Assisted Treatment (MIRROM)

A Phase II Randomized, Double-blind, Placebo-controlled Clinical Trial (RCT) to Evaluate the Ability of Mirtazapine (MZP) to Increase Methamphetamine (MA) Abstinence Among Treatment-seeking Medication for Opioid Use Disorder (MOUD) Adults

This project will evaluate the ability of Mirtazapine (MZP), a pharmacologically unique medication with a growing body of evidence to support its efficacy and safety for the treatment of methamphetamine (MA) use among medication for opioid use disorder (MOUD) patients, to significantly decrease MA use and related health-impairing behaviors. MZP has already successfully been used in the treatment of methamphetamine (detailed further below and in the Appendices).

The investigators hypothesize that those assigned to the MZP plus treatment as usual (TAU) MZP+TAU arm will demonstrate significantly increased rates of biochemically verified abstinence from MA and other substances of abuse and experience improvements in health impairing behaviors relative to the placebo (PLO)+TAU arm across the 10-week treatment and follow-up periods.

Study Overview

• Status: Recruiting
• Conditions: Stimulant Use Disorder
• Intervention / Treatment: Drug: Mirtazapine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Serena M McPherson, BA; Phone Number: (509) 324 7459; Email: s.mcpherson@wsu.edu
• Study Contact Backup: Name: Abigail L Bowen, MS; Phone Number: (509) 638-2376; Email: abigail.bowen@wsu.edu

Study Locations

• United States
  • Washington
    • Spokane, Washington, United States, 99208
      • Recruiting
      • Spokane Treatment Center
      • Contact: Rachel Ryan, BS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Enrollment at medication for opioid use disorder (MOUD) treatment at Oregon Recovery & Treatment Center/clinics in Spokane, WA.
• Verification of a DSM-5104 diagnosis of an methamphetamine (MA) use disorder (i.e. mild, moderate, or severe),
• Aged 18+ years,
• Ability to provide written informed consent,
• Demonstration of 78% adherence rate during the induction period and
• Provision of at least one MA positive urinalysis at baseline or during induction.
• Baseline complete blood cell count (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.
• No current acute illness requiring prolonged medical care.
• No serious chronic illnesses that are likely to progress clinically during trial participation.
• Vital signs are within the normal ranges (i.e., Blood pressure: 90/60 mm Hg to 120/80 mm Hg; breathing: 12-18 breaths per minute; pulse: 60-100 beats per minute; temperature: 97.8 - 99.1 degrees Fahrenheit.

Exclusion Criteria:

• Inability to demonstrate competency to provide informed consent because of cognitive or psychiatric disorders or limited English proficiency,
• Prior diagnosis of dementia,
• Medically or psychiatrically unsafe to participate as determined by Dr. Layton (Medical Director),
• Documented suicide attempt in the past 30 days and/or serious suicide intention or plan as assessed by the Structured Clinical Interview for DSM-5 (SCID-5; clinical trials version)105
• Suicide attempt in the last 2 years
• Moderate or severe liver disease (AST, ALT, and total bilirubin >= 5 times upper limit of normal),
• Impaired renal function (estimated GFR <40 ml/min),
• Current severe cocaine, amphetamine, or alcohol use disorder as defined by DSM-5 criteria which Drs Layton and McPherson deem their participation as unsafe.
• History of bipolar disorder or psychotic disorder, as determined by Structured Clinical Interview for DSM Disorders (SCID,
• Currently taking 1) any type of opioid use disorder medication other than methadone or buprenorphine/naloxone, or 2) phenytoin, carbamazepine, or another inducer of hepatic metabolism (such as rifampicin) and CYP enzyme inhibitor cimetidine.
• Taking an anti-depressant medication within the past 30 days, including mirtazapine or a monoamine oxidase inhibitor,
• Prescribed MZP in the least year, or
• History of violent criminal behavior or being on parole,.
• Currently pregnant or intending to become pregnant,.
• Final determination of eligibility will be made by Dr. Layton in consultation with the PI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MZP+TAU; Mirtazapine + Treatment as Usual	Drug: Mirtazapine; This is a Phase 2, randomized, double-blind, placebo-controlled clinical trial (RCT) to evaluate the ability of mirtazapine (MZP) to increase methamphetamine (MA) abstinence among treatment-seeking medication for opioid use disorder (MOUD) adults.
Placebo Comparator: PLO+TAU; Placebo + Treatment as Usual	Drug: Placebo; Placebo to match.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urinanalysis Verified Increased Days of MA Abstinence	Determine if participants randomized to the MZP+TAU arm use less MA compared to those assigned to the PLO+TAU arm. We hypothesize that those assigned to the MZP+TAU arm will demonstrate significantly increased rates of biochemically verified MA abstinence relative to those in the PLO+TAU arm across the 10-week treatment period and 3-month follow-up periods.	Weeks 2 to Week 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Actigraphy Verified Improved Sleep Patterns	Determine if participants randomized to the MZP+TAU arm demonstrate improvements in sleep compared to those assigned to the PLO+TAU arm. We hypothesize that those assigned to the MZP+TAU arm will demonstrate improvements in objectively verified sleep relative to the PLO+TAU arm across the 10-week treatment and 3-month follow-up periods.	Week 2 to Week 22

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self Reported Quantity of Adverse Events	Determine if participants randomized to the MZP+TAU arm experience the same number of adverse events compared to those in the PLO+TAU arm. We hypothesize that those assigned to the MZP+TAU arm will demonstrate statistically equivalent numbers of adverse events relative to those in the PLO+TAU arm across the 10-week treatment and 3-month follow-up periods.	Week 2 to Week 22
Urinanalysis Verified Increased Days of Abstinence from Other Substances	Determine if participants randomized to the MZP+TAU arm abstain from other substances of abuse (e.g. illicit opioids, cocaine) and demonstrate improvements in MA-associated health-impairing outcomes (e.g. cravings, sleep quality and HIV risk behavior) compared to those assigned to the PLO+TAU arm.	Week 2 to Week 22

Collaborators and Investigators

• Sponsor: Washington State University
• Investigators: Principal Investigator: Sterling M McPherson, PhD, Washington State University

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: March 5, 2024
• First Submitted That Met QC Criteria: March 14, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 27, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Adrenergic Agents; Antidepressive Agents; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Serotonin Agents; Adrenergic Antagonists; Serotonin 5-HT2 Receptor Antagonists; Adrenergic alpha-Antagonists; Histamine H1 Antagonists; Adrenergic alpha-2 Receptor Antagonists; Mirtazapine
• Other Study ID Numbers: 20383

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No