Lisdexamfetamine + Contingency Management for Methamphetamine Addiction

Recruiting at 2 trial locations

Overseen By Didier Jutras-Aswad

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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Lisdexamfetamine for treating methamphetamine addiction?

Lisdexamfetamine is being studied for methamphetamine addiction because it has been effective in treating ADHD with a lower risk of abuse compared to other stimulants. It is a long-acting form of dexamphetamine, which has shown promise in treating methamphetamine dependence in other studies. ^{1 2 3 4 5}

Is lisdexamfetamine generally safe for humans?

Lisdexamfetamine, used for ADHD, has been shown to be generally well tolerated in clinical trials, with most side effects being mild and not increasing with long-term use. It has a lower potential for abuse compared to other stimulants and has been studied for safety in higher doses for methamphetamine dependence. ^{1 4 6 7 8}

How is the drug lisdexamfetamine unique for treating methamphetamine addiction?

Lisdexamfetamine is unique because it is a pro-drug, meaning it is inactive until metabolized in the body, which reduces the potential for abuse compared to other stimulants. It is being studied as a treatment for methamphetamine addiction, a condition with no currently approved medications, offering a novel approach by potentially mimicking the effects of methamphetamine to reduce cravings and withdrawal symptoms. ^{1 2 4 5 9}

Research Team

Didier Jutras-Aswad

Principal Investigator

University of Montreal Hospital Research Center

Eligibility Criteria

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.

I am between 18 and 55 years old.

Participant must be willing to be randomized to one of the 4 study arms and followed for the duration of the trial

Exclusion Criteria

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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, 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Study protocol: a dose-escalating, phase-2 study of oral lisdexamfetamine in adults with methamphetamine dependence. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of oral lisdexamfetamine in adults with methamphetamine dependence: a phase-2 dose-escalation study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Randomized controlled trial of dexamphetamine maintenance for the treatment of methamphetamine dependence. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Lisdexamfetamine: A Review in ADHD in Adults. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. England 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. [2015]

7. Japan pubmed.ncbi.nlm.nih.gov

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

8. New Zealand pubmed.ncbi.nlm.nih.gov

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

9. England 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. [2019]