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

NCT ID: NCT03998852

Last Updated: 2021-06-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-13

Study Completion Date

2022-05-13

Brief Summary

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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.

Detailed Description

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Conditions

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Apathy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Molecular imaging

Positron Emission Tomography (PET) molecular imaging of dopaminergic and cholinergic systems using two radiotracers

Group Type EXPERIMENTAL

Positron Emission Tomography (PET) with [18F]-FDOPA

Intervention Type DRUG

Positron Emission Tomography (PET) with \[18F\]-FDOPA

Positron Emission Tomography (PET) with [18F]-FEOBV

Intervention Type DRUG

Positron Emission Tomography (PET) with \[18F\]-FEOBV

Magnetic Resonnance Imaging (MRI)

Intervention Type DEVICE

MRI protocol will be performed on the same day that the \[18F\]-FEOBV PET imaging, using a 3T scanner (Philips Medical System). Different types of images will be acquired.

Neuropsychological evaluation

Intervention Type OTHER

Neuropsychological evaluation will be performed, consisting in an assessment of apathy by actigraphy (social or physical activities will be recorded during seven days) and a complementary assessment of apathy using the Lille Apathy Rating Scale (LARS)

Interventions

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Positron Emission Tomography (PET) with [18F]-FDOPA

Positron Emission Tomography (PET) with \[18F\]-FDOPA

Intervention Type DRUG

Positron Emission Tomography (PET) with [18F]-FEOBV

Positron Emission Tomography (PET) with \[18F\]-FEOBV

Intervention Type DRUG

Magnetic Resonnance Imaging (MRI)

MRI protocol will be performed on the same day that the \[18F\]-FEOBV PET imaging, using a 3T scanner (Philips Medical System). Different types of images will be acquired.

Intervention Type DEVICE

Neuropsychological evaluation

Neuropsychological evaluation will be performed, consisting in an assessment of apathy by actigraphy (social or physical activities will be recorded during seven days) and a complementary assessment of apathy using the Lille Apathy Rating Scale (LARS)

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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)

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, 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Bordeaux

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Bordeaux University Hospital

Bordeaux, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Nicolas BALAMOUTOFF

Role: CONTACT

05 56 79 55 40

Facility Contacts

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Nicolas BALAMOUTOFF

Role: primary

05 56 79 55 40

Joachim MAZERE

Role: backup

05 57 65 64 08

Other Identifiers

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CHUBX 2017/22

Identifier Type: -

Identifier Source: org_study_id

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