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.
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);
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;
Parallel
Sustained-release Dexamphetamine
DrugDuring 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
DrugDispensed 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 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.
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).
Good or improved overall health is defined as follows: * In patients with physical health problems (Maudsley Addiction Profile; MAP-HSS), or mental health problems (Brief Symptom Inventory; BSI) or problematic social functioning (Social functioning, criminality; European Addiction Severity Index; EuropASI) at baseline, good or improved overall health is defined as: at least 40% improvement in at least one of the 'problematic' health domains, compared with baseline status, assessed at week 24. * In patients without physical health problems, or mental health problems or problematic social functioning at baseline, good or improved overall health is defined as: no deterioration of 40% or more in any of the 'non-problematic' health domains, compared with baseline status, that results in crossing the threshold of health problems, again assessed at week 24. This endpoint concerns the 24-week efficacy of SR-dexamphetamine in terms of overall health.
Secondary outcome measures for the primary study objective: Cocaine use related secondary endpoints: (1) Total number of days cocaine abstinence.
Secondary outcome measures for the primary study objective: Cocaine use related secondary endpoints: (2) Total number of days cocaine abstinence.
Secondary outcome measures for the primary study objective: Cocaine use related secondary endpoints: (3) Complete abstinence from cocaine.
Outcome measure for the exploratory study objective (to explore the cost-utility of 24 weeks SR-dexamphetamine treatment, compared with 24-weeks placebo):
For this purpose, we will use the following exploratory outcomes: * QALYs. * Costs related to treatment, additional health care consumption, and criminality.
Click on the lead sponsor to view all of their trials.
Parnassia Addiction Research Centre
Lead sponsor
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
