Efficacy and Safety of Sustained-release Dexamphetamine in Patients With Moderate to Severe Cocaine Use Disorder
Primary Purpose
Cocaine Use Disorder
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Sustained-release Dexamphetamine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cocaine Use Disorder focused on measuring cocaine use disorder, sustained-release dexamphetamine, agonist pharmacotherapy, opioid use disorder, methadone maintenance treatment, randomized controlled trial (RCT), placebo-controlled, double-blind
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sustained-release Dexamphetamine
Placebo
Arm Description
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.
Identical matched placebo, dispensed under the same conditions and with similar frequency as the investigational product (see above).
Outcomes
Primary Outcome Measures
The number of days of cocaine abstinence
The number of days of cocaine abstinence in the final 4 weeks of treatment, assessed by combined self-report and urinalysis.
Secondary Outcome Measures
Physical health
Physical health; self-reported, Maudsley Addiction Profile - Health Symptoms Scale (MAP-HSS)
Mental health
Mental health; self-reported, Brief Symptom Inventory (BSI)
Social functioning
Social functioning, criminality; self-reported, European Addiction Severity Index (EuropASI)
Full Information
NCT ID
NCT05529927
First Posted
August 19, 2022
Last Updated
September 6, 2022
Sponsor
Parnassia Addiction Research Centre
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
1. Study Identification
Unique Protocol Identification Number
NCT05529927
Brief Title
Efficacy and Safety of Sustained-release Dexamphetamine in Patients With Moderate to Severe Cocaine Use Disorder
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
April 2026 (Anticipated)
Study Completion Date
September 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Parnassia Addiction Research Centre
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
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
204 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sustained-release Dexamphetamine
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Identical matched placebo, dispensed under the same conditions and with similar frequency as the investigational product (see above).
Intervention Type
Drug
Intervention Name(s)
Sustained-release Dexamphetamine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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 Measure Information:
Title
The number of days of cocaine abstinence
Description
The number of days of cocaine abstinence in the final 4 weeks of treatment, assessed by combined self-report and urinalysis.
Time Frame
Final 4 weeks of treatment (first study phase; i.e., week 21-24)
Secondary Outcome Measure Information:
Title
Physical health
Description
Physical health; self-reported, Maudsley Addiction Profile - Health Symptoms Scale (MAP-HSS)
Time Frame
Final 4 weeks of treatment compared with baseline
Title
Mental health
Description
Mental health; self-reported, Brief Symptom Inventory (BSI)
Time Frame
Final 4 weeks of treatment compared with baseline
Title
Social functioning
Description
Social functioning, criminality; self-reported, European Addiction Severity Index (EuropASI)
Time Frame
Final 4 weeks of treatment compared with baseline
Other Pre-specified Outcome Measures:
Title
Discontinuation: Proportion of patients with ≥5 days/month decrease in cocaine abstinent days
Description
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).
Time Frame
Final 4 weeks of treatment discontinuation phase (second study phase; i.e., week 27-30)
Title
Discontinuation: Proportion of patients in good or improved overall health status
Description
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).
Time Frame
Final 4 weeks of treatment discontinuation phase (second study phase; i.e., week 27-30)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peter Blanken, PhD.
Phone
+31623587898
Email
peter.blanken@brijder.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Vincent Hendriks, PhD.
Phone
+31651154583
Email
vincent.hendriks@brijder.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Blanken, PhD.
Organizational Affiliation
Parnassia Addiction Research Centre
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Coded IPD will become available upon reasonable request. Procedures have not yet been determined.
IPD Sharing Time Frame
Not yet determined.
IPD Sharing Access Criteria
Not yet determined.
Citations:
PubMed Identifier
27015909
Citation
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.
Results Reference
background
PubMed Identifier
31908066
Citation
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.
Results Reference
background
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Efficacy and Safety of Sustained-release Dexamphetamine in Patients With Moderate to Severe Cocaine Use Disorder
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