In Vivo Involvement of the Cholinergic and Dopaminergic Systems in the Pathophysiology of Apathy.

Recruiting now · Phase 3

Conditions studied: Apathy

In brief

Apathy is a neurocognitive syndrome characterized by reduced goal-directed behaviors, contributing to decreased patient and caregiver quality of life. Apathy pathophysiology involves disruption of cortico-striato-thalamo-cortical loops, modulated by several neurotransmitter systems including dopamine and acetylcholine, thus complexifying pharmacological management. Post-stroke apathy (PSA) can provide a proper in vivo model to study the underlying neurochemical substrates of apathy as a syndrome. The present project aims to provide a better characterization of the cholinergic and dopaminergic functioning in apathy as a syndrome. In order to precise the respective alterations of these two systems, investigators will use a positron emission tomography (PET) molecular imaging of dopaminergic (with \[18F\]-FDOPA, a marker of the decarboxylating enzyme of dopamine) and - for the first time in apathetic patients - cholinergic (with \[18F\]-FEOBV, a marker of the vesicular acetylcholine transporter) transmissions in 15 apathetic and 15 unapathetic patients 3 months after stroke, without overlapping depression. This dual imaging study may provide help in guiding therapeutic management of PSA. The functional network analysis allowed by functional MRI is crucial to complement regional neurotransmitter deficits observed with PET. Altogether, a multimodal approach in apathy, combining PET and MRI, can allow identifying which circuits of the cortico-striato-thalamo-cortical loops are disrupted and how these circuits are modulated by other neurotransmitters.

Key facts

Study ID: NCT03998852
Run by: University Hospital, Bordeaux
People needed: 30
Starts: 2021-04-13
Expected to finish: 2027-05-13
Last updated by the study team: 2026-06-10

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patient of legal age and younger than 75 years
Patient with a Rankin score less then or equal to 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)

You may not qualify if…

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, Hydroxyzine.
Taking of any pharmacological treatment likely to affect 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)
NYHA Class III to IV Heart Failure Patient
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

Where it is running

Bordeaux University Hospital — Bordeaux, France (enrolling)

Full record on ClinicalTrials.gov

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