E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy volunteers Patients in the chronic stage (> 1 year) after stroke |
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MedDRA Classification |
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 |
The overall purpose of the present proposal is to explore the possibilities offered by pharmacological neuromodulation and brain stimulation in both healthy individuals and in patients with brain damage. Main objective for Part I (Normal volunteers, Patients) of this trial: To enhance procedural motor learning in young and elderly healthy subjects and stroke patients with levodopa premedication . The primary outcome measure is "procedural motor learning (in ms) under levodopa", compared to "procedural motor learning (in ms under placebo". |
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E.2.2 | Secondary objectives of the trial |
For Part II to III of the trial, the main objekctives and outcome measures are:
- Part II: objective: to enhance procedural motor learning for at least 24 hours in young and elderly healthy subjects and stroke patients with both trancranial direct current stimulation and levodopa outcome measure: procedural motor learning after 24 hours (in ms) under levodopa + transcranial direct current stimulation", compared to "procedural motor learning (in ms under placebo+ transcranial direct current stimulation".
- Part III: objective: to examine the underlying neural mechanisms of levodopa-enhanced learning with functional magnetic resonance imaging. outcome measure: "increase in learning-related blood flow in the motor cortex after levodopa", compared to "increase in learning -related blood flow in the motor cortex after placebo" |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Healthy subjects: Only individuals with a normal neurological examination, free of antipsychotic, antidepressant drugs, and drugs affecting the dopaminergic system, and a Mini-Mental-State Examination of > 27 will be included. Chronic stroke patients: They will be eligible if they had a cortical or subcortical stroke with an initial severe hemiparesis MRC scale < 2 that has recovered to a degree that they are able to perform the proposed task (in general > MRC 4.5, with low spasticity, work in progress on motor learning in stroke patients). They will have to be free of antipsychotic and antidepressant drugs, and drugs affecting the dopaminergic system, and a score > 27 on a Mini-Mental-State Examination. Only premorbid right-handed subjects, as assessed by the Edinburgh handedness inventory will be included. |
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E.4 | Principal exclusion criteria |
- Severe and untreated renal and liver insufficiency - Severe and untreated cardiovascular disease, pulmonary disease, endocrine, metabolic, hematopetic disease, - untreated glaucoma - peptic ulcer - melanoma or other skin cancer - intracranial metallic or magnetic implants (other than the mouth) (Part II and Part III) - cardiac pacemaker (Part II and Part III) - Psychiatric disease, neurological disease other than stroke in stroke patient population - antipsychotic or antidepressive medication - known adverse reaction against levodopa or carbidopa - Drug or alcohol (more than 50 mg per day) abuse · - Epilepsy, intracranial tumor - more than 6 cups of coffee per day - more than 15 cigarettes per day - pregnancy (in women of childbearing age; a safe method for contraception and a urine pregnancy test are mandatory)
specifically for stroke patients: - more than one cerebral infarction, or bilateral infarction - brain stem infarction |
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E.5 End points |
E.5.1 | Primary end point(s) |
For the primary outcome measure, procedural motor learning performance (reaction times in ms) after levodopa-premedication, data will be submitted to an analysis of variance (ANOVA) with the factors CONDITION (placebo, levodopa) the factor GROUP (young healthy volunteer (HV), elderly HV, young stroke patient (SP), elderly SP) and the dependent variable test performance, followed by adequate post-hoc tests in the case of significance |
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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 | Yes |
E.6.4 | Safety | No |
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 | Information not present in EudraCT |
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 | Yes |
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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | Information not present in EudraCT |
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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last visit of 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 | |
E.8.9.1 | In the Member State concerned days | |