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

NCT05529927 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 10140262110025
• Study Type: interventional
• Target: 204
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Cocaine Use Disorder

Keywords

cocaine use disorder; sustained-release dexamphetamine; agonist pharmacotherapy; opioid use disorder; methadone maintenance treatment; randomized controlled trial (RCT); placebo-controlled; double-blind

Outcome Measures

Primary Outcomes (1)

• Primary outcome measure for the primary study objective (to evaluate the efficacy of 24 weeks SR-dexamphetamine, compared with 24 weeks placebo): the number of days cocaine abstinence.

  The number of days of cocaine abstinence in the final 4 weeks of treatment, assessed by combined self-report and urinalysis.

  Final 4 weeks of treatment (first study phase; i.e., week 21-24)

Secondary Outcomes (13)

• Key secondary outcome measure for the primary study objective ("good or improved overall health status", in terms of physical health, mental health, and social functioning).

  Final 4 weeks of treatment (i.e. week 21 - week 24) compared with baseline

• Secondary outcome measures for the primary study objective: Cocaine use related secondary endpoints: (1) Total number of days cocaine abstinence.

  During first 12 weeks treatment (i.e., 0-84 days)

• Secondary outcome measures for the primary study objective: Cocaine use related secondary endpoints: (2) Total number of days cocaine abstinence.

  During 24 weeks treatment (i.e., 0-168 days)

• Secondary outcome measures for the primary study objective: Cocaine use related secondary endpoints: (3) Complete abstinence from cocaine.

  During 24 weeks treatment

• Secondary outcome measures for the primary study objective: Cocaine use related endpoints: (4) Achieving a period of sustained abstinence from cocaine for at least 21 consecutive days.

  During 24 weeks treatment

Other Outcomes (1)

• Outcome measure for the exploratory study objective (to explore the cost-utility of 24 weeks SR-dexamphetamine treatment, compared with 24-weeks placebo):

  The first 24 weeks of treatment

Study Arms (2)

Sustained-release Dexamphetamine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Sustained-release Dexamphetamine DRUG

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.

Sustained-release Dexamphetamine

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• severe medical (e.g., severe renal or hepatic insufficiency/failure) or severe psychiatric problems (e.g. previous or acute severe psychotic episode, acute suicidality, current bipolar disorder);
• cardiovascular problems: clinically relevant ECG abnormalities suggestive of channelopathy or structural or ischemic heart disease, or a prolonged QTc interval (≥500 msec); moderate to severe hypertension (i.e., SBP\>140; DBP\>90); HR\>100, known coronary artery disease (i.e., angina pectoris, acute myocardiac infarction), known cardiomyopathy, CVA;
• glaucoma;
• Gilles-de-la-Tourette syndrome;
• pheochromocytoma;
• hyperthyroid status;
• pregnancy or continued lactation;
• use of monoamine oxidase inhibitor(s) (MAOI): currently or in the past 14 days;
• treatment with other prescription psychostimulants that might potentially be effective for stimulant use disorder (i.e., (immediate release) dexamphetamine, lisdexamphetamine, methylphenidate, or modafinil);
• anticipated need for inpatient treatment (clinical judgement);
• (expected) inability to complete the 30 weeks study (e.g., planned holidays, expected incarceration or hospitalization);
• insufficient command of the Dutch language; and
• current participation in another addiction treatment study.

Sponsors & Collaborators

• Parnassia Addiction Research Centre: lead
• Leiden University Medical Center: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Radboud University Medical Center: collaborator
• The Netherlands Cancer Institute: collaborator
• Het Zwarte Gat: collaborator

Related Publications (2)

• Nuijten M, Blanken P, van de Wetering B, Nuijen B, van den Brink W, Hendriks VM. Sustained-release dexamfetamine in the treatment of chronic cocaine-dependent patients on heroin-assisted treatment: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 May 28;387(10034):2226-34. doi: 10.1016/S0140-6736(16)00205-1. Epub 2016 Mar 22.

  PMID: 27015909 BACKGROUND

• Blanken P, Nuijten M, van den Brink W, Hendriks VM. Clinical effects beyond cocaine use of sustained-release dexamphetamine for the treatment of cocaine dependent patients with comorbid opioid dependence: secondary analysis of a double-blind, placebo-controlled randomized trial. Addiction. 2020 May;115(5):917-923. doi: 10.1111/add.14874. Epub 2020 Jan 6.

  PMID: 31908066 BACKGROUND

MeSH Terms

Conditions

Opioid-Related Disorders

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Vincent Hendriks, PhD.

  Parnassia Addiction Research Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vincent Hendriks, PhD.

CONTACT

+31651154583; vincent.hendriks@brijder.nl

Tjitske Colenbrander, MsC, MD.

CONTACT

+31616046159; t.colenbrander@brijder.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 19, 2022
• First Posted: September 7, 2022
• Study Start: May 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): October 1, 2029
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Not yet determined.
• Access Criteria: Not yet determined.