Clinical trial NCT06788587: Feasibility of Long-term, High-dose Stimulant for Methamphetamine Use Disorder
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Methamphetamine Abuse
Methamphetamine-dependence
Addiction
Substance Abuse
Methamphetamine Use Disorder
Keywords: Substance use disorder
Amphetamines
Methamphetamine
Lisdexamfetamine
Treatment
Agonist therapy
Feasibility
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: Ministere de la Sante et des Services Sociaux
name: Health Canada
First posted: 2025-01-23
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-centre, 2-arm, randomized, double-blind, dose-ascending, placebo-controlled extension trial. Participants will be enrolled into one of 2 treatment arms:

* Arm 1: LDX-01 + TAU
* Arm 2: Placebo + TAU
Primary purpose: TREATMENT

Brief summary: Methamphetamine use disorder (MUD) is becoming an increasing public health concern in Canada. While the evidence on the efficacy and safety of prescription psychostimulants for the treatment of MUD is promising, the knowledge on the maintenance therapy using stimulant agonist therapy is scarce and needs further investigation, especially in terms of long-term retention in treatment.

The goal of this clinical trial is to evaluate the feasibility of a long-term (25 weeks) administration of high-dose stimulant agonist therapy, using Lisdexamfetamine (LDX-01) on top of treatment-as-usual (TAU), in a population of people with moderate to severe MUD, as measured by study retention, treatment retention, treatment adherence and satisfaction compared against a placebo group.

Participants will be placed randomly into one of two groups:

1. TAU and high-dose LDX-01
2. TAU and placebo

Detailed description: This trial is a single-centre, randomized double-blind (LDX-01), dose-ascending, placebo-controlled trial. This study is an extension to a parent trial, Addition of high-dose stimulant and engagement-focused contingency management, alone and in combination, to treatment as usual for the management of methamphetamine use disorder (ASCME): a pan-Canadian multi-centre, randomized, controlled trial (NCT05854667). Participants will be enrolled in one of the 2 treatment arms:

Arm 1 : TAU plus high-dose LDX-01 Arm 2 : TAU plus placebo

The trial will enroll 62-80 participants who have completed the parent trial in the Quebec site. The participants will be enrolled in the trial for 30 weeks.

Participation includes the following:

1. Participants will receive medication or placebo weekly for 25 weeks
2. Participants will attend the clinic for weekly treatment
3. Participants will attend the clinic once every week for study visits. At these visits, participants will be asked to provide a urine sample (Weeks 1-25: every two weeks, week 26 and week 30) and/or complete questionnaires

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.

Primary outcomes:
measure: Retention in treatment
timeFrame: Weeks 18, 19, 20, 21 and weeks 22, 23, 24, 25
measure: Treatment satisfaction
timeFrame: Weeks 22, 26
measure: Retention in study
timeFrame: Weeks 22, 26 and 30
measure: Treatment adherence
timeFrame: from week 1 day 1 to week 25
Secondary outcomes:
Other outcomes:
measure: Safety events
timeFrame: up to 30 weeks : from the date of enrollment until week 30
measure: QTc measurement
timeFrame: Screening, weeks 1, 2, 3, 7 and 22
measure: Self-reported methamphetamine use
timeFrame: Baseline, week 1 day 1, weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 26 and 30
measure: Methamphetamine use by urinalysis
timeFrame: week 1 day 1, weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 26 and 30
measure: Amphetamine craving
timeFrame: week 1 day 1, weeks 12, 22, 26 and 30
measure: Addiction severity
timeFrame: week 1 day 1, weeks 12, 22, 26 and 30
measure: Quality of life
timeFrame: week 1 day 1, weeks 12, 22, 26 and 30
Locations:
city: Montreal
country: Canada
facility: Centre hospitalier de l'Université de Montréal (CHUM)
state: Quebec
Study officials:
affiliation: CHUM
name: Didier Jutras-Aswad, MD
role: PRINCIPAL_INVESTIGATOR
References: