Adherence to Stimulant Treatment in Attention-Deficit Hyperactivity Disorder (ADHD) Patients (ASTA)

Study Overview
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Brief Summary
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This study determined to measure non-adherence assessed by the number of non-adherent days during the clinical trial of 100 days using the Medication Event Monitoring System (MEMS). Study Design: prospective multi-centric open-label randomized active-controlled trial

Detailed Description
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The study is designed as a prospective, multi-centric, open-label, randomized, active-controlled trial. ADHD-children and adolescents of both sexes, 6-17 of age, effectively treated with stimulants are recruited in two centres. Over a naturalistic run-in phase of four weeks adherence to medication taken before randomisation is measured. In the subsequent controlled clinical trial 50% of the participants are randomized to extended release (ER) methylphenidate (Medikinet retard®) applied with breakfast, 50% are randomized to immediate release (IR) methylphenidate (Medikinet®) in the morning and 3-4 h later (clinical trial). To optimize ecological validity, no double-dummy technique is applied; the allocation to either study arm is non-blinded. According to the power calculation 106 patients will be randomized. The total duration of the study is 18 months. Starting with a run-in visit, each eligible patient is observed in the naturalistic run-in phase for four weeks. Subsequently, patients participate 100 days in the clinical trial starting with a baseline visit, an in between-visit and a final visit. Medical care is provided in the routine program of both study centres. To record the adherence, medication events are counted by Medication Event Monitoring System (MEMS).

Official Title
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Effect of Methylphenidate Formulation on ADHD-patients' Adherence to Medical Treatment. A Comparison of Medikinet Retard® (ER) Once Daily and Medikinet® (IR) Twice Daily in Children and Adolescents Diagnosed With ADHD

Conditions
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ADHD

Intervention / Treatment
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* Drug: Immediate release methylphenidate (Medikinet®)
* Drug: Extended release methylphenidate (Medikinet retard®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent (separately for children aged 6-11 years and 12-17 years) Children and adolescents of both sexes aged 6 - 17 years Confirmed diagnosis of ADHD by semi structured-clinical interview K-SADS ADHDRS-IV-Parent Version (18-Item-Scale) raw score ≥ 1,5 SD above norm under non-medicated conditions (either drug holiday or prior to medication within the past 6 months) Effective treatment with a stable dose of methylphenidate for at least one month (max. 60 mg/day) proved by a 25% symptom reduction in ADHD-RS under medication, compared to retrospective ADHD-RS without medication within the past 6 months. Acceptance and capability to swallow capsules of product size, proved by an equally sized placebo provided by Medice®. Sufficient knowledge of the German language Adequate contraception in case of sexual activity Exclusion Criteria: Contraindications against methylphenidate Previous stable methylphenidate intake more than twice daily All severe psychiatric disorders except oppositional defiant disorder (ODD) or conduct disorder. In order to reflect the usual co-morbid spectrum of ADHD, mild or moderate anxiety or depressive disorders are accepted in the study. All severe somatic diseases as assessed by the baseline examination or medical history (including life-time history of epileptic disorders) Pathological results for vital signs, blood pressure and pulse Reported pathological results for ECG during the last 12 months Reported pathological results for differential blood count and hepatic metabolism during the last 6 months Indication for hospitalization Suicidality (assessed by MADRS Item 10, Score ≥ 3) IQ < 70 (clinically assessed) Any psychotropic co-medication Detention in an institution on official or judicial ruling Unwillingness to transmit pseudonym data according to German regulations Simultaneous participation in another clinical trial according to German Drug Law (AMG)

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate release<br>Treatment with immediate release (IR) methylphenidate (Medikinet®) in the morning and 3-4 h later (twice a day) | Drug: Immediate release methylphenidate (Medikinet®)<br>* Treatment: methylphenidate in the morning and 3-4 h later (twice daily), immediate release<br>* Other names: Medikinet®;|
| Active Comparator: Extended release<br>Treatment with extended release (ER) methylphenidate (Medikinet reatard®) applied with breakfast(once daily) | Drug: Extended release methylphenidate (Medikinet retard®)<br>* Treatment: methylphenidate applied with breakfast(once daily), extended release<br>* Other names: Medikinet retard®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Non-adherence assessed by the number of non-adherent days during the clinical trial of 100 days using the Medication Event Monitoring System (MEMS) |  | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of non-adherent days measured by pill count |  | 100 days | 
| Time interval until a total number of 30 days of non-adherence is reached cumulatively during the clinical trial measured by MEMS |  | 100 days | 
| Quality of life during measured by Child Health Illness Profile - Child Edition (CHIP-CE) Score |  | 100 days | 
| The efficacy of stimulant treatment during the clinical trial measured by ADHD-Rating Scale- Parent Version Sum Score |  | 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD, children, adolescents, methylphenidate, adherence, immediate release, extended release, efficacy