Methylphenidate for Cocaine Dependence (ANRS STIMAGO)

Pilot Study to Evaluate the Benefits and the Risks of Methylphenidate for the Treatment of Cocaine Dependence

This phase II pilot study aims at evaluating the benefits and the risks of methylphenidate (Concerta®) for the treatment of cocaine/crack dependence in terms of cocaine/crack use reduction and adverse events.

Study Overview

• Status: Withdrawn
• Conditions: Substance-Related Disorders
• Intervention / Treatment: Drug: Methylphenidate Pill

Detailed Description

Patients will receive pharmacotherapy based on methylphenidate (18 mg per tablet) with a 3-week titration phase to a maximum dose of 108 mg per day, with a weekly follow-up during 3 months. Socio-demographic and behavioral data will be collected through phone interviews every month. During medical visits, self-administered and clinical questionnaires will collect clinical and behavioral data. Urine drug toxicologies and blood sampling will be performed to gather biological, pharmacokinetic and pharmacodynamic data.

This study should identify an effective response-dose of methylphenidate for people with a cocaine use disorder. The methylphenidate should be effective to reduce cocaine use in cocaine-dependent individuals with a good tolerability. The results of pharmacokinetic and pharmacodynamic analyses will give us the effective dose of methylphenidate and some information on toxicity to adapt the surveillance in a future clinical trial.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Villejuif, France, 94800
    • Hopital Paul Brousse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed with cocaine/crack/amphetamine derivate dependence using Diagnostic and Statistical Manual of Mental Disorders (DSM V) (and International Classification of Diseases (ICD 10)) and willing to be abstinent.
• Having a cocaine/crack positive urinary test.
• Effective contraception for women of childbearing age.
• Willing to participate.
• Registered at social insurance/security.
• Being able to give consent.
• Reachable by telephone.

Exclusion Criteria:

• Dependence on alcohol and/or other substances.
• Hypersensitivity to the active compound methylphenidate or to filler.
• Glaucoma.
• Phaeochromocytoma
• Family history or diagnosis of Gilles de la Tourette syndrome.
• During treatment with non-selective, irreversible monoamine oxidase (MAO) inhibitors.
• History of hyperthyroidism or of thyrotoxicosis.
• Preexisting cardiovascular problems including severe hypertension, heart failure, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening arrythmias and channelopathies, (disorders caused by the dysfunction of ionic channels).
• Preexisting cerebrovascular disorders, cerebral aneurism, vascular abnormalities including vasculitis or stroke.
• Diagnosis or history of severe depression, anorexia nervosa/anorexic disorders, suicidal tendencies, psychotic symptoms, severe mood disorders, mania, schizophrenia, psychopathic/borderline personality disorder
• Diagnosis or history of severe and episodic (Type I) Bipolar (affective) Disorder (that is not well-controlled)
• Suicidal tendencies or characterized suicidal syndrome.
• Pregnancy, breast-feeding or absence of any contraception for female participants.
• Unstabilized psychiatric comorbidity likely to compromise adherence to treatment.
• Comorbidity or handicap likely to corrupt evaluation.
• Organic pathology severe enough according to the investigator, likely to comprise adequate surveillance during the trial.
• Patient about to leave the area for a period of time preventing his/her adequate participation in the trial.
• Insufficient motivation.
• Participation in another clinical trial with an on-going exclusion period at the time of the pre-inclusion visit.
• Lack of medical insurance.
• Unreachable by phone.
• Patient on mandatory treatment.
• Patient with legal incapacity (under guardianship or curatorship)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Methylphenidate pill; 18 mg tablets with a 3-week titration phase to a maximum dose of 108 mg per day, orally Associated with phone interviews every month, urine drug toxicologies and blood sampling (PK/PD)	Drug: Methylphenidate Pill; 3-month follow-up to study the effective dose as a treatment for cocaine dependence in toxicity and reduction in cocaine use; Other Names: Concerta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cocaine use	Difference between weekly cocaine use at M0 and M3 based on the patient self-reports and urinalysis	Evaluated through the study: during the titration phase (day 1, day 4, day 8, day 11, day 15, day 18) and then at the week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11 and week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects using the Drug Effects questionnaire (DEQ)	Number of perceived side effects of methylphenidate with the Drug Effects questionnaire (DEQ)	Evaluated at the week 1, week 2, week 4, week 9 and week 12
Craving using the Cocaine Craving Questionnaire (CCQ 10-item)	Cocaine craving with the Cocaine Craving Questionnaire (CCQ 10-item)	Evaluated during the titration phase (day 1, day 4, day 8, day 11, day 15, day 18) and then at each visit of the two last months (1 visit a week for 2 months)
Abstinence (urinalysis)	Cocaine abstinence with urinalysis	Evaluated during the titration phase (day 1, day 8, day 15, day 18) and then at the week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11 and week 12
Risk practices using the Blood Borne Virus Transmission Risk Assessment Questionnaire (BBV-TRAQ)	Reduction in Hepatitis C (HCV) risk practices, unsafe sex, sharing syringes - Blood Borne Virus Transmission Risk Assessment Questionnaire (BBV-TRAQ)	Evaluated at the week 1, week 4, week 9 and week 12
Psychiatric symptoms - Depression using the Center for Epidemiologic Studies - Depression Scale (CES-D)	Reduction in psychiatric symptoms with the Center for Epidemiologic Studies - Depression Scale (CES-D)	Evaluated at the week 1, week 4, week 9 and week 12
Psychiatric symptoms - Attention/Deficit using the attention-deficit/hyperactivity disorder Scale (ADHD)	Reduction in psychiatric symptoms with the attention-deficit/hyperactivity disorder Scale (ADHD)	Evaluated at the week 1, week 4, week 9 and week 12
Psychiatric symptoms - Sensation Seeking using the 6-item Sensation Seeking Scale (SSQ 6-item)	Reduction in psychiatric symptoms with the 6-item Sensation Seeking Scale (SSQ 6-item)	Evaluated at the week 1, week 4, week 9 and week 12
Criminal behaviors	Reduction in self-reported criminal behaviors by questionnaire	Evaluated at the week 1, week 4, week 9 and week 12
Quality of life using the the 12-Item Short Form Health Survey (SF-12)	Increase of quality of life score with the 12-Item Short Form Health Survey (SF-12)	Evaluated at the week 1, week 4, week 9 and week 12

Collaborators and Investigators

• Sponsor: ANRS, Emerging Infectious Diseases
• Collaborators: Hopital Paul Brousse
• Investigators: Principal Investigator: Amine Benyamina, Pr, Hôpital Paul Brousse APHP - France

Publications and helpful links

Helpful Links

• Sponsor of the study

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2018
• Primary Completion (ANTICIPATED): December 31, 2018
• Study Completion (ANTICIPATED): March 30, 2019

Study Registration Dates

• First Submitted: March 14, 2017
• First Submitted That Met QC Criteria: March 23, 2017
• First Posted (ACTUAL): March 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 20, 2018
• Last Update Submitted That Met QC Criteria: July 19, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: ADHD; pharmacokinetics; cocaine; methylphenidate; crack; psychostimulant; effective dose
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Cocaine-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: ANRS STIMAGO; 2013-002996-16 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No