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Efficacy and Safety of Sustained-release Dexamphetamine in Patients With Moderate to Severe Cocaine Use Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05529927
Recruitment Status : Not yet recruiting
First Posted : September 7, 2022
Last Update Posted : November 18, 2023
Sponsor:
Collaborators:
Leiden University Medical Center
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Radboud University Medical Center
The Netherlands Cancer Institute
Het Zwarte Gat
Columbia University
Information provided by (Responsible Party):
Peter Blanken, PhD, Parnassia Addiction Research Centre

Brief Summary:

In The Netherlands, each year, about 15 thousand people come into treatment because of problems with cocaine use. There is no approved medication for treatment of cocaine addiction and the psychosocial treatment patients receive is not successful for everyone; many return to treatment several times. There is evidence that agonist ("replacement") medications are effective in treating addiction: methadone for heroin addiction; nicotine replacement for smokers. Dexamphetamine is a stimulant medication registered for treatment of ADHD. It may also be effective as agonist treatment for people with cocaine addiction.

It will be investigated whether sustained-release dexamphetamine in people with cocaine addiction, participating in routine methadone maintenance treatment for their comorbid opioid use disorder, (1) reduces cocaine use and (2) improves their health and quality of life.


Condition or disease Intervention/treatment Phase
Cocaine Use Disorder Drug: Sustained-release Dexamphetamine Drug: Placebo Phase 2

Detailed Description:

RESEARCH QUESTION/RATIONALE: Treatment for patients with cocaine use disorder is modestly effective and there is an urgent need for more effective treatments. Several randomized controlled trials, including our previous proof of principle study (Nuijten et al., 2016, The Lancet), suggest that sustained-release dexamphetamine is the most promising medication for the treatment of cocaine use disorder.

HYPOTHESIS & OBJECTIVES: Therefore, it is hypothesized that sustained-release dexamphetamine is effective in patients with cocaine use disorder in terms of reducing cocaine use and improving health and quality of life.

STUDY DESIGN: Multicentre randomized, double-blind, placebo-controlled study in 204 patients with cocaine use disorder - participating in routine methadone maintenance treatment for their comorbid opioid use disorder. In the 1st study phase (24 weeks) the efficacy and safety of sustained-release dexamphetamine is compared with placebo. In the 2nd double-blind, placebo-controlled randomized treatment discontinuation phase (6 weeks), we assess the consequences of discontinuation of sustained-release dexamphetamine treatment.

STUDY POPULATION: Patients with moderate/severe cocaine use disorder participating in routine oral methadone maintenance treatment for their comorbid opioid use disorder .

INTERVENTION: The investigational product is in tablets, containing 30 mg dexamphetamine sulphate in sustained-release formulation. Patients will be titrated to the target dose of 90 mg/day, if tolerated. Medication is dispensed twice weekly.

OUTCOME PARAMETERS: Primary endpoint: number of days of cocaine abstinence in the final 4 weeks of treatment, assessed by combined self-report and urinalysis. Key secondary endpoint: Good or improved overall health status (in terms of physical and mental health, and social functioning).

SAMPLE SIZE/DATA-ANALYSIS: Assuming 5 days difference in cocaine abstinent days in the final 4 weeks of the study to be clinically relevant requires 102 patients per treatment group in order to detect these 5 days difference (pooled standard deviation: 11 days; two-sided alpha=0.05; power=0.90). Primary analysis: The primary endpoint is modelled in a negative binomial regression analysis, with treatment group as independent variable and stratification variables (treatment centre, overall health status, and (nearly) daily cocaine use) as covariates.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 204 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of 24 Weeks Sustained-release Dexamphetamine in Patients With Moderate to Severe Cocaine Use Disorder With Comorbid Opioid Use Disorder - A Multicenter Randomized, Double-blind, Placebo-controlled Study
Estimated Study Start Date : March 2024
Estimated Primary Completion Date : October 2026
Estimated Study Completion Date : April 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Sustained-release Dexamphetamine
Tablets of 30 mg sustained-release dexamphetamine sulphate. Target dose: 90 mg/day, if tolerated. Tablets have to be taken daily, in the morning, per os for 24 weeks.
Drug: Sustained-release Dexamphetamine

During the first week, patients will be individually titrated to the target dose of 90 mg/day, if tolerated. From the second week onwards, patients are prescribed 3 tablets (30 mg) per day, if tolerated. Titration can be slower but should be finished at the end of week 4. After 4 weeks dosages can no longer be increased, and only be reduced.

Patients will visit the treatment centre 2 times per week to take their study medication under supervision of the treatment staff and to receive take-home medication for the days in between study visits.

After 24 weeks patients will be randomized to either (double-blind) continuation or discontinuation (placebo) of SR-Dexamphetamine treatment to assess the consequences of discontinuation, during a 6 weeks period.


Placebo Comparator: Placebo
Identical matched placebo, dispensed under the same conditions and with similar frequency as the investigational product (see above).
Drug: Placebo

Dispensed under the same conditions and with similar frequency as the investigational product (see above).

After 24 weeks study medication will be discontinued in the placebo group.





Primary Outcome Measures :
  1. The number of days of cocaine abstinence [ Time Frame: Final 4 weeks of treatment (first study phase; i.e., week 21-24) ]
    The number of days of cocaine abstinence in the final 4 weeks of treatment, assessed by combined self-report and urinalysis.


Secondary Outcome Measures :
  1. Physical health [ Time Frame: Final 4 weeks of treatment compared with baseline ]
    Physical health; self-reported, Maudsley Addiction Profile - Health Symptoms Scale (MAP-HSS)

  2. Mental health [ Time Frame: Final 4 weeks of treatment compared with baseline ]
    Mental health; self-reported, Brief Symptom Inventory (BSI)

  3. Social functioning [ Time Frame: Final 4 weeks of treatment compared with baseline ]
    Social functioning, criminality; self-reported, European Addiction Severity Index (EuropASI)


Other Outcome Measures:
  1. Discontinuation: Proportion of patients with ≥5 days/month decrease in cocaine abstinent days [ Time Frame: Final 4 weeks of treatment discontinuation phase (second study phase; i.e., week 27-30) ]
    Proportion of patients with ≥5 days/month decrease in cocaine abstinent days at end of discontinuation phase (compared with the number of cocaine abstinent days/month at the end of study phase 1; weeks 21-24).

  2. Discontinuation: Proportion of patients in good or improved overall health status [ Time Frame: Final 4 weeks of treatment discontinuation phase (second study phase; i.e., week 27-30) ]
    Proportion of patients in good or improved overall health status at end of discontinuation phase (compared with the proportion of patients in good or improved overall health at the end of study phase 1; weeks 21-24).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • male and female patients between 18 and 65 years of age;
  • active participation in opioid agonist treatment with oral methadone;
  • moderate or severe cocaine use disorder according to DSM-5;
  • regular use of cocaine in the previous month (i.e., ≥8 days/month);
  • snorting, inhaling or injecting cocaine use as primary route of administration;
  • the intention to reduce or stop cocaine use;
  • able and willing to attend the treatment centre for 2 days per week;
  • able and willing to co-operate with the required study assessments and study procedures; and
  • provide written informed consent.

Exclusion Criteria:

  • severe medical (e.g., severe renal or kidney insufficiency/failure) or severe psychiatric problems (e.g. acute psychosis, current major depression, current bipolar disorder, acute suicidality);
  • cardiovascular problems: clinically relevant ECG abnormalities, moderate to severe hypertension (SBP>140; DBP>90; HR>100), angina pectoris, history with myocardial infarction, CVA, heart failure;
  • glaucoma;
  • Gilles-de-la-Tourettesyndrome;
  • pheochromocytoma;
  • hyperthyroid status;
  • current dyspnea;
  • pregnancy or continued lactation;
  • (indication for) treatment with other medications that might potentially be effective for stimulant use disorder (e.g., methylphenidate, disulfiram, bupropion, or modafinil);
  • anticipated need for inpatient treatment (clinical judgement);
  • (expected) inability to complete the 30 weeks study (e.g., due to expected incarceration or hospitalization);
  • insufficient command of the Dutch language; and
  • current participation in another addiction treatment study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05529927


Contacts
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Contact: Peter Blanken, PhD. +31623587898 peter.blanken@brijder.nl
Contact: Vincent Hendriks, PhD. +31651154583 vincent.hendriks@brijder.nl

Sponsors and Collaborators
Parnassia Addiction Research Centre
Leiden University Medical Center
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Radboud University Medical Center
The Netherlands Cancer Institute
Het Zwarte Gat
Columbia University
Investigators
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Principal Investigator: Peter Blanken, PhD. Parnassia Addiction Research Centre
Publications:
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Responsible Party: Peter Blanken, PhD, Senior researcher, Parnassia Addiction Research Centre
ClinicalTrials.gov Identifier: NCT05529927    
Other Study ID Numbers: 10140262110025
First Posted: September 7, 2022    Key Record Dates
Last Update Posted: November 18, 2023
Last Verified: November 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Coded IPD will become available upon reasonable request. Procedures have not yet been determined.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Not yet determined.
Access Criteria: Not yet determined.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Peter Blanken, PhD, Parnassia Addiction Research Centre:
cocaine use disorder
sustained-release dexamphetamine
agonist pharmacotherapy
opioid use disorder
methadone maintenance treatment
randomized controlled trial (RCT)
placebo-controlled
double-blind
Additional relevant MeSH terms:
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Opioid-Related Disorders
Narcotic-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Dextroamphetamine
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents