Clinical Trial of High Dose Lisdexamfetamine and Contingency Management in MA Users

Official title

Addition of High Dose Stimulant and Engagement-focused Contingency Management (CM), Alone and in Combination, to Treatment as Usual (TAU) for the Management of Methamphetamine (MA) Use Disorder (ASCME): a Canadian Multi-centre, RCT

Overview

The goal of this clinical trial is to learn if administering a high dose stimulant with Contingency Management reduces days of use in adults who use methamphetamine better than the usual treatment provided by the clinic. The main questions the trial aims to answer are: Is a high dose stimulant better than a placebo and usual treatment at helping reduce the number of days they use methamphetamine? Is a high dose stimulant with contingency management better than placebo and usual treatment at helping people reduce the number of days they use methamphetamine? Participants will be placed randomly into one of four groups: 1. Usual treatment and placebo 2. Usual treatment, placebo and contingency management 3. Usual treatment and high dose stimulant 4. Usual treatment, high dose stimulant and contingency management Participation includes the following: 1. Participants will receive medication or placebo weekly for 15 weeks. 2. Participants will attend the clinic for weekly treatment 3. Participants will attend the clinic once every 2 weeks for study visits. Each visit will take about an hour to complete. At these visits, participants will be asked to provide a urine sample and complete questionnaires.

Detailed description

The ASCME trial is a multi-centre, randomized double blind (lisdexamfetamine-01 component), open label (Contingency Management component), dose-ascending, placebo controlled trial. Participants will be enrolled in one of the 4 treatment arms:

Arm 1: treatment as usual plus placebo Arm 2: treatment as usual plus placebo and contingency management Arm 3: treatment as usual plus lisdexamfetamine (LDX-01) Arm 4: treatment as usual plus lisdexamfetamine (LDX-01) and contingency management

The trial will enroll 440 participants, and will be conducted in 5-7 treatment centres across Canada.

Participants will be enrolled in the trial for 20 weeks altogether.

Interventions

• Drug Treatment as Usual plus Placebo
  Participants receive once daily Lisdexamfetamine matched placebo for 15 weeks, as well as treatment as usual at clinical site.
• Drug Treatment as Usual plus Placebo plus Contingency Management
  Participants receive once daily Lisdexamfetamine matched placebo for 15 weeks, as well as treatment as usual at clinical site, and engagement-focused contingency management for 12 weeks, week 2-13.
• Drug Treatment as Usual plus lisdexamfetamine (LDX-01)
  Participants receive once daily Lisdexamfetamine for 15 weeks, as well as treatment as usual at clinical site. Medication is provided in 3 phases: Week 1 (Induction Phase): 100 mg (Day 1 and 2), 150 mg (Day 3 and 4), 200 mg (Day 5, 6 and 7) Weeks 2-13 (Maintenance Phase): 250 mg per day (or the maximum tolerated for each individual) and then will continue on the same daily dose Weeks 14-15 (Taper Phase): 150 mg (Week 14) and 50 mg (Week 15).
• Drug Treatment as Usual plus lisdexamfetamine (LDX-01) plus Contingency Management
  Participants receive once daily Lisdexamfetamine for 15 weeks, as well as treatment as usual at clinical site. Medication is provided in 3 phases: Week 1 (Induction Phase): 100 mg (Day 1 and 2), 150 mg (Day 3 and 4), 200 mg (Day 5, 6 and 7) Weeks 2-13 (Maintenance Phase): 250 mg per day (or the maximum tolerated for each individual) and then will continue on the same daily dose Weeks 14-15 (Taper Phase): 150 mg (Week 14) and 50 mg (Week 15). Engagement-focused contingency management will be pro

Primary outcome measures

• Total number of days of methamphetamine use during maintenance phase [Time frame: 12 weeks]

Secondary outcome measures (7)

• Medication Adherence [Time frame: 15 weeks]
• Safety Events [Time frame: 20 weeks]
• Changes in Quality of Life [Time frame: Will be administered at Baseline, Week 8, 14 and 20.]
• Methamphetamine and other Substance Use - self report [Time frame: 15 weeks]
• Methamphetamine and other Substance Use - urine drug screen [Time frame: 15 weeks]
• Indigenous wellness perspective [Time frame: Administered at Baseline, week 8, 14 and 20]
• Treatment Satisfaction [Time frame: Week 14 only]

Eligibility criteria

Inclusion criteria

• Participant must meet all the following criteria:

• Between 18 and 55 years of age;
• Diagnosed with a moderate to severe methamphetamine (MA) use disorder as defined by the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) criteria;
• Active MA use at screening measured via self-reported MA use ≥14 days in the past 28 days AND verified by urine drug metabolite testing;
• Interested in reducing/stopping MA use;
• 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;
• Willing to be randomized to one of the 4 study arms and followed for the duration of the trial;
• Able to provide informed consent;
• Willing to comply with study procedures;
• Able to communicate in English or French.

Exclusion criteria

• 1\. Symptomatic or advanced cardiovascular disease (e.g., advanced arteriosclerosis), moderate hypertension; current hyperthyroidism confirmed via blood test; known hypersensitivity or idiosyncrasy to the sympathomimetic amines or glaucoma or any disabling, severe, OR unstable medical condition 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 Therapy (OAT) for < 12 weeks, and not yet at stabilization dose, or at stabilization dose < 4 weeks; 4. Current or 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 severe adverse event, hypersensitivity or known allergic reaction to LDX 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 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 prior to screening, confirmed via self-report OR pharmacy records; 9. Currently receiving contingency management for the treatment of stimulant use disorder in the 4 weeks prior to screening, confirmed via self-report OR site records; 10. Use of prescribed amphetamine-type medication OR medication for the treatment of stimulant use disorder (e.g., methylphenidate, modafinil, bupropion) in the 4 weeks prior to screening; 11. Current or anticipated need for treatment with any medication that may interact with LDX (e.g., proton pump inhibitors, 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Canada · 4 centers

• Rapid Access Addiction Medicine Clinic, St. Paul's Hospital — Vancouver
• River Stone Recovery Centre — Fredericton
• Center for Addiction and Mental Health — Toronto
• University of Montreal Hospital Research Center — Montreal

Publications

• Bach P, Le Foll B, Davidson S, de Kiewit A, Bakouni H, Poulin G, Ghosh M, Jutras-Aswad D. A protocol for high-dose lisdexamfetamine and contingency management, alone or in combination, for the treatment of methamphetamine use disorder: The ASCME study. Contemp Clin Trials. 2025 Jun;153:107916. doi: 10.1016/j.cct.2025.107916. Epub 2025 Apr 13. PMID 40233849

Identifiers

NCT: NCT05854667 · 23.053

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗