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
Between 18 and 55 years of age at enrollment in the parent ASCME trial;
Diagnosed with a moderate to severe MUD as defined by the DSM-5 criteria;
Enrolled in the parent ASCME trial and completed the study up to and including the end of study visit at Week 20, Day 1;
Interested in avoiding relapse, decreasing methamphetamine use, or abstaining from methamphetamine use;
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;
Any severe or unstable co-morbid substance use disorder that, in the opinion of the study physician, precludes safe participation in the study;
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;
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;
Parallel
LDX-01 plus TAU
DrugParticipants receive once daily LDX-01 for 25 weeks, as well as TAU at a clinical site. Medication is provided in 3 phases: Week 1 (Induction Phase): 100 mg (Days 1 and 2), 150 mg (Days 3 and 4), 200 mg (Days 5, 6 and 7); Weeks 2-21 (Maintenance Phase): 250 mg (or the maximum tolerated for each individual) ; Weeks 22-25 (Taper Phase): 200 mg (Week 22), 150 mg (Week 23), 100 mg (Week 24) and 50 mg (Week 25).
Placebo plus TAU
DrugParticipants receive once daily LDX-01-matched placebo for 25 weeks, as well as TAU at a clinical site. Medication is provided in 3 phases: Week 1 (Induction Phase): 100 mg (Days 1 and 2), 150 mg (Days 3 and 4), 200 mg (Days 5, 6 and 7); Weeks 2-21 (Maintenance Phase): 250 mg (or the maximum tolerated for each individual) ; Weeks 22-25 (Taper Phase): 200 mg (Week 22), 150 mg (Week 23), 100 mg (Week 24) and 50 mg (Week 25).
Retention in treatment
Retention in treatment will be measured as the proportion of study participants who receive any intervention during the 4 weeks before week 22 and 4 weeks before week 26
Treatment satisfaction
Participant treatment satisfaction will be measured by evaluating participant satisfaction using the Client Satisfaction Questionnaire-8 (CSQ-8) questionnaire. The total score ranges from 8 (minimum) to 32 (maximum) with the higher values showing greater satisfaction.
Retention in study
Retention in study will be measured as 1) the proportion of study participants who return for the study visit at week 22 with or without receiving the study interventions, 2) the proportion of study participants who return for the study visit at week 26 with or without receiving the study interventions, and 3) the proportion of study participants who return for the last study visit at week 30 with or without receiving the study interventions.
Treatment adherence
Treatment adherence will be first, measured individually, as the total proportion of the number of the assigned medications (LDX-01/placebo) taken through the intervention (from baseline until the end of week 25) and then averaged across all study completers.
Safety events
Safety of long-term high-dose LDX-01 will be assessed through the collection of adverse event (AEs) and serious adverse event (SAEs). The number and proportions of each AE, SAE, adverse drug reaction (ADR), and unexpected ADR will be recorded weekly. For calculations, each participant's safety-related event will be counted once under the maximum severity or the strongest recorded causal relationship to study medication
QTc measurement
QTc will be measured using ECG; incidence of borderline prolonged (460-479 milliseconds for females and 450-469 milliseconds for males) and prolonged ( ≥ 480 milliseconds for females and ≥ 470 milliseconds for males) QTc interval will be measured using the Bazett method for the correction of QT interval.
Self-reported methamphetamine use
Self-reported methamphetamine use, is measured using the self-reported number of days of methamphetamine use during the 29 weeks of the study using the Timeline Follow Back (TLFB) Questionnaire since the last study visit, or in the past 28 days, whichever number of days is the least (i.e., researcher-administered, with memory cues to improve accuracy).
Methamphetamine use by urinalysis
Methamphetamine use by urinalysis will be measured by the number of reactive urine samples tested for methamphetamine using the rapid chromatographic immunoassays for urine drug screen (UDS). All urine specimens will be collected and analyzed using a Rapid Response Multi- Drug One Step Screen Test Panel, following the manufacturer's recommended procedures to test for the presence of the following drugs or their respective metabolites: methamphetamine, morphine, fentanyl, benzodiazepines, cocaine, THC, methadone, buprenorphine, methylphenidate, MDMA, LSD, ketamine, oxycodone, heroin, Hydromorphone and amphetamine (week 30 only). A validity check will be performed using an adulterant strip included in the test.
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Centre hospitalier de l'Université de Montréal (CHUM)
Lead sponsor
Ministere de la Sante et des Services Sociaux
Collaborator
Health Canada
Collaborator
