In vivo involvement of the cholinergic and dopaminergic systems in the pathophysiology of apathy. ADACHOL.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Bordeaux

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Trial duration

13 Apr 2021 → ongoing

Decision date (initial)

2024-11-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

LabEx BRAIN

External identifiers

EU CT number

2024-518721-15-00

EudraCT number

2018-003286-34

ClinicalTrials.gov

NCT03998852

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Others

To compare the integrity of cholinergic and dopaminergic pathways in apathetic (n = 15) and unapathetic (n = 15) patients, 3 to 7 months after stroke, matched in age and sex. It will be necessary to compare the binding intensity of cholinergic and dopaminergic tracers between the 2 groups of subjects.

Secondary objectives 4

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

Conditions and MedDRA coding

Apathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Patient of legal age and younger than 75 years
2. Patient with a Rankin score less than or equal to 2 and with or without apathy, demonstrated by AI scales, 3 to 7 months after stroke (apathetic patient = AI scale score > 2)
3. Affiliate or beneficiary of a social security scheme
4. Subjects (female study subjects and female partners of male participants) using highly effective contraceptive methods (intra-uterine device, progestin or estrogen-progestin contraceptive, sterilization)
5. 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)

Exclusion criteria 16

1. Patients over 75 years old
2. 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, Hydroxyzine
3. Taking of any pharmacological treatment likely to affect and dopaminergic systems at the time of PET-scan: glucagon, haloperidol, reserpin
4. White matter T2 hyperintense lesions (Fazekas score > 4)
5. NYHA Class III to IV Heart Failure Patient
6. Patients with allergy or conter-indication to entacapone
7. Subjects with positive pregnancy test ((BHCG dosage and Urine dipstick), and/or currently breast-feeding
8. Patients unable to come back to hospital for at least 2-follow-up visit
9. Patient with a chronic neurological disorder or severe psychiatric disorder
10. Patient presenting a counter-indication for MRI
11. Patient presenting a counter-indication for TEP with [18F]-FEOBV or [18F]-FDOPA (known allergy)
12. Patient who underwent a PET examination in the previous month
13. Patient with state of health not allowing a displacement in the department of imaging of the CHU: bedridden state, state of health very deteriorated
14. Patient deprived of liberty by judicial or administrative decision
15. Patient under legal protection or unable to express its own consent
16. Subject within exclusion period from another clinical trial

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. [18F]-FEOBV and [18F]-FDOPA binding intensities

Secondary endpoints 4

1. Clinical severity of apathy
2. Functional connectivity parameters measured with MRI
3. Diffusion tensor imaging parameters, such as the fractional anisotropy and mean diffusivity, measured with structural MRI
4. Cerebral blood flow

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Bordeaux

Sponsor organisation

Centre Hospitalier Universitaire De Bordeaux

Address

12 Rue Dubernat

City

Talence

Postcode

33400

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Principal Investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Principal Investigator

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications