E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002942 |
E.1.2 | Term | Apathy |
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042244 |
E.1.2 | Term | Stroke |
E.1.2 | System Organ Class | 100000004852 |
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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 compare the integrity of cholinergic and dopaminergic pathways in apathetic (n = 15) and unapathetic (n = 15) patients 3 months after stroke, matched in age and sex. It will be necessary to compare the binding intensity of cholinergic and dopaminergic tracers (estimated in PET by the measurement of either the nondisplaceable Binding Potential, BPND, or a binding ratio) between the 2 groups of subjects. |
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E.2.2 | Secondary objectives of the trial |
1. To assess whether modifications of cholinergic and dopaminergic activities can be linked with the clinical expression of apathy.
2. To assess whether cholinergic and dopaminergic dysfunctions can be linked with alterations in the functional organization of the resting brain.
3. To assess whether modifications of cholinergic and dopaminergic activities can be linked with specific local changes in white matter microstructure.
4. To investigate whether the binding intensity of cholinergic and dopaminergic tracers is dependent on cerebral blood flow disorders, as shown on the cerebral blood flow maps provided by arterial spin labeling sequences.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patient of legal age and younger than 75 years - Patient with a Rankin score 2 and with or without apathy, demonstrated by AI scales at 3 months after stroke (apathetic patient = AI scale score > 2) - Affiliate or beneficiary of a social security scheme - Subjects (female study subjects and female partners of male participants) using highly effective contraceptive methods (intra-uterine device, progestin or estrogen-progestin contraceptive, sterilization) - Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research)
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E.4 | Principal exclusion criteria |
- Patients over 75 years old - Taking of any pharmacological treatment likely to affect cholinergic systems at the time of PET-scan : Amitriptyline, Atropine, Brompheniramine, Chlorphenamine, Chlorpromazine, Clomipramine, Clozapine, Dimenhydrinate, Diphenhydramine, Doxepine, Hyoscyamine, Imipramine, Meclozine, Nortriptyline, Oxybutynine, Promethazine, Scopolamine, Trimipramine - Taking of any pharmacological treatment likely to affect and dopaminergic systems at the time of PET-scan: glucagon, haloperidol, reserpin - Taking of any selective serotonine reuptake inhibitors treatment - White matter T2 hyperintense lesions (Fazekas score > 3) - Patients with allergy or conter-indication to entacapone - Subjects with positive pregnancy test ((BHCG dosage and Urine dipstick), and/or currently breast-feeding - Patients unable to come back to hospital for at least 2-follow-up visits - Patient with a chronic neurological disorder or severe psychiatric disorder - Patient with cognitive impairment (MoCA<24) and depression (CES-D score > 17 for men and >23 for women) - Patient presenting a counter-indication for MRI - Patient presenting a counter-indication for TEP with [18F]-FEOBV or [18F]-FDOPA (known allergy) - Patient who underwent a PET examination in the previous month - Patient with state of health not allowing a displacement in the department of imaging of the CHU: bedridden state, state of health very deteriorated - Patient deprived of liberty by judicial or administrative decision - Patient under legal protection or unable to express its own consent - Subject within exclusion period from another clinical trial
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E.5 End points |
E.5.1 | Primary end point(s) |
[18F]-FEOBV nondisplaceable binding potential (BPND) and [18F]-FDOPA binding ratio |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Binding intensity of cholinergic and dopaminergic tracers - Clinical severity of apathy - Functional connectivity parameters measured with MRI - Diffusion tensor imaging parameters, such as the fractional anisotropy and mean diffusivity, measured with structural MRI - Cerebral blood flow
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Pathophysiology of apathy |
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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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Patient without apathy (control group) |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
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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 | No |
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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LVLP (if IRM is the last visit) or 24 hours after injection (to research adverse event) if LVLP corresponds to a PET imaging. |
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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 | |
E.8.9.1 | In the Member State concerned months | 25 |
E.8.9.1 | In the Member State concerned days | |