E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This project investigates whether the effects of methylfenidate on the outgrowth of the dopaminergic system are dependent on age. In a 16 week multicenter, dounle-blind, placebo controlled trial with methylfenidate in 100 children and adults suffering from ADHD, the effect of age is investigated using state of the art in vivo Magnetic Resonance Imaging (MRI) techniques that allow determination of the functional status of the dopaminergic system. |
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E.1.1.1 | Medical condition in easily understood language |
We investigate the effects of methylphenidate (Ritalin) on the brain using MRI by
treating 100 children and adults diagnosed with ADHD with methylphenidate or placebo for 16 weeks. |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064104 |
E.1.2 | Term | ADHD |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056941 |
E.1.2 | Term | MRI brain |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To report on the age-dependency of the effect(s) of MPH treatment on the outgrowth of the DA system using state-of-the-art Magnetic Resonance Imaging (MRI) techniques |
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E.2.2 | Secondary objectives of the trial |
1. To report on the age-dependency of MPH on the outgrowth of the DA system using several functional outcome measures (functional MRI (fMRI), neuropsychological test battery)
2. To report on the effects of MPH on restless legs syndrome (RLS) symptoms and insomnia
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
50 adolescent (10-12 years of age) and 50 adult (23-30 years of age) male outpatients diagnosed with type ADHD, all subtypes as defined in the DSM-IV, and in need of pharmacotherapy according to existing guidelines. |
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E.4 | Principal exclusion criteria |
-Co-morbid Axis I psychiatric disorders requiring treatment with medication at study entry, and a history of epilepsy and traumatic brain injury.
-IQ < 70 (subtest Wechsler Intelligence Scale for children-Revised (WISC-R; Wechsler 1981) or National Adult Reading Test (NART; Nelson 1991, Dutch translation Schmand et al. 1991)
- Current or previous treatment with medications that influence the DA system (for adults before 23 years of age) such as: neuroleptics, antipsychotics, D2/D3 agonists (pramipexole and ropinirole)
-Current or previous (ab)use of drugs that influence the DA system (for adults before 23 years of age), such as: MDMA, amphetamine, methamphetamine, cocaine, heroine and LSD
-Contraindications to MPH treatment: cardiovascular diseases such as hypertension, arrhythmia, hyperthyroidism, glaucoma, suicidality, psychosis, Tourette disorder.
-Prenatal use of MPH by mother of the patients.
-Contraindications to MRI (metal implants, pacemakers, claustrophobia, etc.)
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary study parameters/endpoints:
- phMRI: % change in ASL signal from baseline in response to acute oral MPH challenge before and after 16 weeks of MPH treatment
- DTI: % change in FA and MD values from baseline after 16 weeks of MPH treatment
- Resting state fMRI (rs-fMRI): % change in functional connectivity (FC) within specific (DA) neuronal networks
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
In week 0 (baseline), week 8 and week 18 |
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E.5.2 | Secondary end point(s) |
-fMRI: % change in task related BOLD signal from baseline
-Neuropsychological functioning: change in outcome of several well-validated neuropsychological (computer) tasks addressing emotional processing and impulsivity/behavioral inhibition compared to baseline measurements.
-Sleep log and actigraph: % change from baseline
-DLMO: % change from baseline
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
In week -1 (from baseline), week 0,week 7, week 8, week 17 and week 18 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last visit of the last subject undergoing the trial, |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |