Lisdexamfetamine + Contingency Management for Methamphetamine Addiction

Recruiting at 3 trial locations

Overseen By Amina Sow

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Amphetamines, MAOIs, Proton pump inhibitors

Disqualifiers: Cardiovascular disease, Hypertension, Opioid use disorder, Psychiatric disorders, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 17

Duration: 15 weeks

440 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if lisdexamfetamine, a stimulant medication, combined with a reward-based strategy called Contingency Management, can help reduce methamphetamine use. Participants will be divided into four groups to test different combinations: usual treatment with a placebo, usual treatment with the stimulant, and both with Contingency Management. The trial seeks adults diagnosed with moderate to severe methamphetamine use disorder who are actively using methamphetamine but wish to reduce their use. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot use certain medications like amphetamine-type drugs or those that interact with LDX (a stimulant) within 14 days before starting the trial. It's best to discuss your current medications with the study team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that lisdexamfetamine is generally safe for adults, even at high doses like 250 mg per day. In studies, most participants tolerated the medication well, and researchers found no major safety issues. Some individuals might experience side effects, but these are usually mild and manageable. Lisdexamfetamine has been used for other conditions, providing a wealth of safety information. Overall, the treatment appears safe for most individuals considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using lisdexamfetamine for methamphetamine addiction because it offers a new approach compared to existing treatments. While standard options like behavioral therapies and support groups focus on managing cravings and behavior, lisdexamfetamine is a medication that could directly impact the brain's chemistry. Lisdexamfetamine is a prodrug of dextroamphetamine, which means it's converted in the body to an active stimulant that may help balance neurotransmitters and reduce the urge to use methamphetamine. Additionally, the trial combines this medication with contingency management, a behavioral strategy that rewards positive behavior, potentially enhancing treatment effectiveness. This integrated approach could provide a more comprehensive solution for those struggling with methamphetamine addiction.

What evidence suggests that this trial's treatments could be effective for methamphetamine addiction?

Research has shown that lisdexamfetamine can help people reduce methamphetamine use over a 12-week period. However, strong evidence does not support the continuation of this reduction long-term. In this trial, some participants will receive lisdexamfetamine, while others will receive a placebo. Previous studies found lisdexamfetamine safe for treating withdrawal symptoms from methamphetamine. When combined with contingency management, a reward-based treatment, the focus is on reducing self-reported methamphetamine use and keeping people in treatment longer. Overall, lisdexamfetamine, especially when combined with contingency management, shows promise in helping people cut back on methamphetamine use. ^{1 2 4 6 7}

Who Is on the Research Team?

Didier Jutras-Aswad

Principal Investigator

University of Montreal Hospital Research Center

Are You a Good Fit for This Trial?

Adults aged 18-55 with moderate to severe methamphetamine (MA) addiction, actively using MA, and interested in reducing or stopping use. Women must be non-pregnant, non-nursing, and if of childbearing potential, agree to use birth control. Excludes those with serious heart disease, hypertension, hyperthyroidism; severe psychiatric disorders; recent other substance abuse treatments; or on certain medications.

Inclusion Criteria

I am following the required birth control guidelines due to my childbearing potential.

Participant must be diagnosed with a moderate to severe methamphetamine (MA) use disorder as defined by the DSM-5 criteria

I have used methamphetamine on 14 or more days in the last month, confirmed by a urine test.

Exclusion Criteria

Participant with severe or unstable co-morbid substance use disorder, Opioid Use Disorder (OUD) with specific treatment duration criteria, serious psychiatric disorders, history of severe adverse events or allergic reactions to specific medications, pregnancy, nursing, or planning to become pregnant during the study period, planned extended absence during study period, use of investigational drugs for stimulant use disorder, receiving contingency management for stimulant use disorder, use of prescribed amphetamine-type medication or medication for the treatment of stimulant use disorder, current or anticipated need for treatment with medications that may interact with LDX

I do not have severe or unstable heart, thyroid, eye conditions, or allergies that would make it unsafe for me to participate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive medication or placebo weekly for 15 weeks, with weekly clinic visits and bi-weekly study visits for urine samples and questionnaires.

15 weeks

Weekly clinic visits, bi-weekly study visits

Maintenance

The primary outcome measure is assessed during this 12-week period, focusing on the total number of days of methamphetamine use.

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with adverse events tracked up to week 20.

5 weeks

Visits at week 16 and 20

What Are the Treatments Tested in This Trial?

Interventions

• Lisdexamfetamine

Trial Overview The trial tests whether high dose lisdexamfetamine (LDX), a stimulant medication combined with Contingency Management (rewards for meeting treatment goals), is more effective than placebo at reducing MA use when added to usual treatment. Participants are randomly assigned to one of four groups: usual treatment plus placebo, with or without Contingency Management; or usual treatment plus LDX-01, with or without Contingency Management.

How Is the Trial Designed?

Group I: Treatment as Usual plus lisdexamfetamine (LDX-01) Active Control 1 Intervention

Participants will receive treatment as usual at the clinic as well as once daily over-encapsulated lisdexamfetamine (LDX-01) orally for 15 weeks.

Group II: Treatment as Usual plus lisdexamfetamine (LDX-01) plus Contingency Management Active Control 1 Intervention

Participants will receive treatment as usual at the clinic, once daily over-encapsulated lisdexamfetamine (LDX-01) orally for 15 weeks, as well as engagement-focused contingency management.

Group III: Treatment as Usual plus Placebo Placebo Group 1 Intervention

Participants will receive treatment as usual at the clinic as well as once daily lisdexamfetamine matched Placebo orally for 15 weeks.

Group IV: Treatment as Usual plus Placebo plus Contingency Management Placebo Group 1 Intervention

Participants will receive treatment as usual at the clinic, once daily lisdexamfetamine matched placebo medication orally for 15 weeks, as well as engagement-focused contingency management.

Lisdexamfetamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Vyvanse for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Moderate to severe binge eating disorder (BED)

Approved in European Union as Vyvanse for:

• Attention Deficit Hyperactivity Disorder (ADHD)

Approved in Canada as Vyvanse for:

• Attention Deficit Hyperactivity Disorder (ADHD)
• Moderate to severe binge eating disorder (BED)

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

Lisdexamfetamine mesylate (Vyvanse) has a lower potential for abuse compared to immediate-release d-amfetamine, as indicated by lower 'Drug liking' scores in drug-experienced individuals and its unique pharmacokinetic profile.

In animal studies, lisdexamfetamine produced smaller but more sustained increases in dopamine levels and less locomotor activation than d-amfetamine, suggesting a better therapeutic window with fewer stimulant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisdexamfetamine and immediate release d-amfetamine - differences in pharmacokinetic/pharmacodynamic relationships revealed by striatal microdialysis in freely-moving rats with simultaneous determination of plasma drug concentrations and locomotor activity. Rowley, HL., Kulkarni, R., Gosden, J., et al.[2015]

Lisdexamfetamine (LDX) at doses up to 250 mg/day was found to be safe and well tolerated among 16 adults with methamphetamine dependence, with 87.5% of participants completing the treatment regimen.

The study showed a significant reduction in methamphetamine use, with participants reporting a decrease from a median of 21 days of use to 13 days over the 4-week escalation period, indicating potential efficacy in treating methamphetamine dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of oral lisdexamfetamine in adults with methamphetamine dependence: a phase-2 dose-escalation study. Ezard, N., Clifford, B., Dunlop, A., et al.[2022]

Lisdexamfetamine, a prodrug stimulant, was successfully used to treat ADHD in a 33-year-old male with a history of stimulant use disorder, leading to significant improvements in focus and organization without exacerbating anxiety or sleep issues.

The patient experienced a notable reduction in cravings for stimulants and maintained sobriety, demonstrating that lisdexamfetamine can be a safe and effective treatment option for individuals with ADHD and a history of stimulant abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Lisdexamfetamine to Treat ADHD in a Patient with Stimulant (Methamphetamine) Use Disorder. Levine, J., Swanson, H.[2023]

Lisdexamfetamine, a prodrug that converts to d-amphetamine in the body, effectively treats ADHD by increasing dopamine and noradrenaline levels, as shown in clinical studies conducted in Japan and internationally.

The drug has a favorable safety profile, with most side effects being mild and no increase in adverse events or treatment discontinuation rates observed with long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological properties and clinical effects of the ADHD drug, Lisdexamfetamine (Vyvanse® capsules 20 mg and 30 mg)]. Sakai, C.[2020]

This phase 2 study will assess the safety and tolerability of lisdexamfetamine at doses of 100 to 250 mg in 20 individuals with methamphetamine dependence over an 8-week period, aiming to establish its potential as a treatment option.

The study will also evaluate secondary outcomes such as changes in methamphetamine use, cravings, and withdrawal symptoms, which could provide insights into the drug's efficacy in reducing dependence and improving overall treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol: a dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence. Ezard, N., Dunlop, A., Clifford, B., et al.[2018]

In a randomized trial with 49 participants, those receiving sustained-release dexamphetamine showed significantly better treatment retention (86.3 days) compared to the placebo group (48.6 days), indicating its potential effectiveness in supporting recovery from methamphetamine dependence.

Dexamphetamine treatment was associated with a significant reduction in methamphetamine dependence and withdrawal symptoms, and it was found to be safe, with no serious adverse events reported during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized controlled trial of dexamphetamine maintenance for the treatment of methamphetamine dependence. Longo, M., Wickes, W., Smout, M., et al.[2018]

Lisdexamfetamine dimesylate is a prodrug stimulant designed for the treatment of ADHD, offering a longer duration of effect and a predictable release of the active drug, d-amphetamine, which helps reduce variability in patient response.

This medication has a lower potential for abuse compared to traditional stimulant medications, making it a safer option for children and adolescents with ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisdexamfetamine in the treatment of adolescents and children with attention-deficit/hyperactivity disorder. Najib, J.[2021]

A double-blind randomized controlled trial is underway to evaluate the efficacy of lisdexamfetamine (LDX) in reducing methamphetamine use among 180 participants with a history of dependence, aiming to assess both the effectiveness and safety of LDX over a 15-week treatment period.

The study will measure primary outcomes such as changes in self-reported methamphetamine use and confirmatory urinalyses, while also exploring secondary outcomes related to mental health, treatment retention, and cost-effectiveness, providing a comprehensive evaluation of LDX as a potential treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LiMA: a study protocol for a randomised, double-blind, placebo controlled trial of lisdexamfetamine for the treatment of methamphetamine dependence. Ezard, N., Dunlop, A., Hall, M., et al.[2019]

Lisdexamfetamine is a long-acting ADHD medication that has shown significant improvements in ADHD symptoms and overall functioning compared to placebo in three short-term trials involving adults, making it a promising treatment option.

It is generally well tolerated and offers a convenient once-daily dosing regimen, which may enhance adherence and reduce the potential for abuse compared to short-acting amphetamines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lisdexamfetamine: A Review in ADHD in Adults. Frampton, JE.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39701142/

Lisdexamfetamine in the treatment of methamphetamine ... Lisdexamfetamine appears to reduce methamphetamine use over a 12-week treatment period, although there is only weak evidence that reduced use is maintained ...

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/add.16730

Lisdexamfetamine in the treatment of methamphetamine ... Lisdexamfetamine appears to reduce methamphetamine use over a 12-week treatment period, although there is only weak evidence that reduced use is ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40233849/?utm_source=WordPress&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1XmaK3PTZdu971PXDnBoT7mB0jFG6Cvxnl4ctsJC3rIS1-DIvB&fc=20250217093552&ff=20250416043433&v=2.18.0.post9+e462414

A protocol for high-dose lisdexamfetamine and ... The primary outcome is reduction in days of self-reported methamphetamine use, with secondary outcomes including treatment retention, sustained ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S037687162200429X

Lisdexamfetamine for the treatment of acute ... A tapering dose regimen of lisdexamfetamine was safe and feasible for the treatment of acute methamphetamine withdrawal in an inpatient setting.

5. bmjopen.bmj.com bmjopen.bmj.com/content/8/7/e020723

LiMA: a study protocol for a randomised, double-blind ... We hypothesise that treatment with oral lisdexamfetamine will result in significantly reduced methamphetamine use at 13 weeks compared with placebo in people ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8137170/

Safety and tolerability of oral lisdexamfetamine in adults ... To examine the safety of an agonist-type treatment, lisdexamfetamine (LDX), at 250 mg/day among adults with methamphetamine (MA) dependence.

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2833773

Safety of Stimulants Across Patient Populations: A Meta- ... Another RCT of dextroamphetamine transdermal system in individuals with methamphetamine dependence found no significant differences in AEs ...