Long-term high-dose lisdexamfetamine treatment for methamphetamine use disorder

Exploring Feasibility and Acceptability of Prolonged Administration of High-Dose Stimulants in People With Methamphetamine Use Disorder: An Extension of a Randomized, Placebo-Controlled Trial

This trial will try giving adults with moderate to severe methamphetamine use disorder a 25-week course of high-dose lisdexamfetamine plus their usual care to see if it helps them stay in treatment and cut down on methamphetamine use compared with placebo.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM) (Academic / other)
• Locations: 1 site (Montreal, Quebec)
• Trial ID: NCT06788587 on ClinicalTrials.gov

What this trial studies

This is a single-center, randomized, double-blind, dose-ascending, placebo-controlled extension trial conducted at CHUM in Montreal, enrolling 62–80 participants who completed the parent ASCME trial at the Quebec site. Participants are randomized to weekly high-dose lisdexamfetamine plus treatment-as-usual or placebo plus treatment-as-usual for a 25-week medication period and will attend weekly clinic visits. Urine samples and questionnaires are collected regularly (biweekly urines during Weeks 1–25 and additional samples at Weeks 26 and 30) to track adherence, retention, and methamphetamine use. The primary focus is feasibility outcomes including study retention, treatment retention, adherence, and participant satisfaction compared against placebo.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18–55 with moderate to severe methamphetamine use disorder who completed the parent ASCME trial at the CHUM Quebec site, have ongoing use, craving, or relapse risk, and can attend weekly clinic visits.

Not a fit: People who did not complete the parent trial, who do not have moderate-to-severe MUD, who are pregnant or planning pregnancy, or who are stable without ongoing use or relapse risk are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this approach could help people stay in treatment longer, reduce methamphetamine use, and lower the risk of relapse.

How similar studies have performed: Previous trials of prescription stimulants for stimulant use disorders have shown some promising short-term results, but long-term, high-dose lisdexamfetamine maintenance remains largely untested and this protocol is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Between 18 and 55 years of age at enrollment in the parent ASCME trial;
2. Diagnosed with a moderate to severe MUD as defined by the DSM-5 criteria;
3. Enrolled in the parent ASCME trial and completed the study up to and including the end of study visit at Week 20, Day 1;
4. Interested in avoiding relapse, decreasing methamphetamine use, or abstaining from methamphetamine use;
5. Presence of ongoing substance use, craving, or significant risk of relapse that according to the study physician, warrants extended treatment for MUD;
6. If female:

   * Be of non-childbearing potential, defined as (i) postmenopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age); or (ii) documented surgically sterilized (i.e., tubal ligation, hysterectomy, or bilateral oophorectomy); or
   * Be of childbearing potential, have a negative pregnancy test at screening, and agree to use an acceptable method of birth control throughout the study;
7. Willing to be randomized to one of 2 study arms and followed for the duration of the trial;
8. Able to start the study intervention within 28 days after completing the ASCME main trial (study no. CRISM-002);
9. Able to provide informed consent;
10. Willing to comply with study procedures;
11. Able to communicate in English or French

Exclusion Criteria:

1. Symptomatic or advanced cardiovascular disease (e.g., advanced arteriosclerosis), moderate hypertension; confirmed current hyperthyroidism; known hypersensitivity or idiosyncrasy to the sympathomimetic amines or glaucoma or any disabling, severe, or unstable medical condition (including electrolyte disturbances) that, in the opinion of the study physician, precludes safe participation or the ability to provide fully informed consent;
2. Any severe or unstable co-morbid substance use disorder that, in the opinion of the study physician, precludes safe participation in the study;
3. Participants with Opioid Use Disorder (OUD) who have been on Opioid Agonist Treatment (OAT) for \<12 weeks, and not yet at stabilization dose, or at stabilization dose \<4 weeks;
4. Current or a history of any serious psychiatric disorder (e.g., bipolar disorder, pre-existing psychosis, schizophrenia) that, in the opinion of the study physician, precludes safe participation in the study;
5. History of a SAE, hypersensitivity or known allergic reaction to LDX-01 or other amphetamine drugs, or hypersensitivity to the sympathomimetic amines;
6. Pregnant, nursing, or planning to become pregnant during the study period;
7. Planned extended absence during the study period (e.g., pending legal action, surgery, incarceration, inpatient residential program) in the opinion of the study physician that might prevent completion of the study;
8. Use of an investigational drug for stimulant use disorder during the 30 days before screening, confirmed via self-report or pharmacy records; excluding the use of study medication in the parent ASCME trial;
9. Use of prescribed amphetamine-type medication or medication for the treatment of stimulant use disorder (e.g., methylphenidate, modafinil, bupropion, or mirtazapine) in the 4 weeks before screening;
10. Current or anticipated need for treatment with any medication that may interact with LDX-01 (e.g., monoamine oxidase inhibitors \[MAOIs\]) used currently or within the past 14 days and that would preclude study participant at the discretion of the study physician;
11. ECG measurement (Bazett method for the correction of QT interval) that indicates a prolonged QTc interval (≥460 milliseconds for females and ≥450 milliseconds for males) at screening;
12. Any SAEs related to the study product in the parent trial phase that, in the opinion of the study physician, precludes safe participation in the extension study;
13. Any compliance issues related to the study product and/or study procedures during the parent trial phase that, in the opinion of the study physician, precludes safe participation in the extension study.

Where this trial is running

Montreal, Quebec

• Centre hospitalier de l'Université de Montréal (CHUM) — Montreal, Quebec, Canada (Recruiting)

Study contacts

• Principal investigator: Didier Jutras-Aswad, MD — Chum
• Study coordinator: Devon Blanchette

Conditions Methamphetamine Abuse; Methamphetamine-dependence; Addiction; Substance Abuse; Methamphetamine Use Disorder; Substance use disorder; Amphetamines; Methamphetamine