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

NCT03998852 | Unknown Phase 3

• 1 other identifier: CHUBX 2017/22
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Apathy

Keywords

Apathy; Stroke; Cholinergic neurotransmission; Dopaminergic neurotransmission

Outcome Measures

Primary Outcomes (2)

• [18F]-FDOPA SUVr

  Standardized uptake value for the \[18F\]-FDOPA radiotracer

  Between 7 and 30 days after first visit

• [18F]-FEOBV SUVr

  Standardized uptake value for the \[18F\]-FEOBV radiotracer

  First visit (Day 0)

Secondary Outcomes (8)

• Apathy Inventory Score

  First visit (Day 0)

• Beck Anxiety Inventory (BAI) Score

  First visit (Day 0)

• Lille Apathy Rating Scale (LARS) Score

  First visit (Day 0)

• Multidimensional Fatigue Inventory (MFI) Score

  First visit (Day 0)

• Center of Epidemiology Studies Depression Scale (CES-D) Score

  First visit (Day 0)

Study Arms (1)

Molecular imaging

EXPERIMENTAL

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

Drug: Positron Emission Tomography (PET) with [18F]-FDOPA; Drug: Positron Emission Tomography (PET) with [18F]-FEOBV; Device: Magnetic Resonnance Imaging (MRI); Other: Neuropsychological evaluation

Interventions

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

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

Molecular imaging

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

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

Molecular imaging

Magnetic Resonnance Imaging (MRI) 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.

Molecular imaging

Neuropsychological evaluation 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)

Molecular imaging

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (1)

Bordeaux University Hospital

Bordeaux, 33076, France

RECRUITING

MeSH Terms

Conditions

Lethargy; Stroke

Interventions

Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole; fluorodopa F 18

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Central Study Contacts

Nicolas BALAMOUTOFF

CONTACT

05 56 79 55 40; nicolas.balamoutoff@chu-bordeaux.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2019
• First Posted: June 26, 2019
• Study Start: April 13, 2021
• Primary Completion: April 13, 2022
• Study Completion: May 13, 2022
• Last Updated: June 1, 2021

Record last verified: 2021-05

Locations

FR (1)