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

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ClinicalTrials.gov Identifier: NCT03998852
Recruitment Status : Not yet recruiting
First Posted : June 26, 2019
Last Update Posted : March 31, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux

Tracking Information
First Submitted Date  ICMJE June 20, 2019
First Posted Date  ICMJE June 26, 2019
Last Update Posted Date March 31, 2020
Estimated Study Start Date  ICMJE June 1, 2020
Estimated Primary Completion Date June 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
  • [18F]-FDOPA SUVr [ Time Frame: Between 7 and 30 days after first visit ]
    Standardized uptake value for the [18F]-FDOPA radiotracer
  • [18F]-FEOBV SUVr [ Time Frame: First visit (Day 0) ]
    Standardized uptake value for the [18F]-FEOBV radiotracer
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 24, 2019)
  • Apathy Inventory Score [ Time Frame: First visit (Day 0) ]
    Apathy score from 0 to 36. Apathetic patient = score >2
  • Beck Anxiety Inventory (BAI) Score [ Time Frame: First visit (Day 0) ]
    Beck Anxiety Inventory (BAI). Score from . Anxiety = score > 22
  • Lille Apathy Rating Scale (LARS) Score [ Time Frame: First visit (Day 0) ]
    Complementary assessment of apathy. Score from - 36 to 36. Score < - 22 : no apathy
    • 21 to -17 : apathy tendancy
    • 16 to -10 : moderate apathy
    • 9 to 36 : severe apathy
  • Multidimensional Fatigue Inventory (MFI) Score [ Time Frame: First visit (Day 0) ]
    The MFI contains 20 items classified into four dimensions : general fatigue, mental fatigue, reduced activities and motivation. The statements are rated on a 5-point Likert scale (from "Yes, that is true" to "No, that is not true") representing the patient's current feeling. Low MFI scores reflect a higher degree of fatigue.
  • Center of Epidemiology Studies Depression Scale (CES-D) Score [ Time Frame: First visit (Day 0) ]
    Center of Epidemiology Studies Depression Scale (CES-D) The frequency of occurrence of symptoms is measured with a 4 points scale : o = Never
    1. = Occasionally
    2. = Quite often
    3. = Frequently The total score is between 0 and 60. Highest scores correspond to the presence of a more severe depressive symptomatology Depressive patients = score > 17 for men and >23 for women
  • Fractional anisotropy [ Time Frame: First visit (Day 0) ]
    Fractional anisotropy measured with structural MRI
  • Mean diffusivity [ Time Frame: First visit (Day 0) ]
    Mean diffusivity measured with structural MRI
  • Cerebral blood flow maps [ Time Frame: First visit (Day 0) ]
    Cerebral blood flow maps provided by arterial spin labeling sequences
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE In Vivo Involvement of the Cholinergic and Dopaminergic Systems in the Pathophysiology of Apathy.
Official Title  ICMJE In Vivo Involvement of the Cholinergic and Dopaminergic Systems in the Pathophysiology of Apathy.
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Condition  ICMJE Apathy
Intervention  ICMJE
  • Drug: Positron Emission Tomography (PET) with [18F]-FDOPA
    Positron Emission Tomography (PET) with [18F]-FDOPA
  • Drug: Positron Emission Tomography (PET) with [18F]-FEOBV
    Positron Emission Tomography (PET) with [18F]-FEOBV
  • Device: 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.
  • Other: 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)
Study Arms  ICMJE Experimental: Molecular imaging
Positron Emission Tomography (PET) molecular imaging of dopaminergic and cholinergic systems using two radiotracers
Interventions:
  • Drug: Positron Emission Tomography (PET) with [18F]-FDOPA
  • Drug: Positron Emission Tomography (PET) with [18F]-FEOBV
  • Device: Magnetic Resonnance Imaging (MRI)
  • Other: Neuropsychological evaluation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 24, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2022
Estimated Primary Completion Date June 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nicolas BALAMOUTOFF 05 56 79 55 40 nicolas.balamoutoff@chu-bordeaux.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03998852
Other Study ID Numbers  ICMJE CHUBX 2017/22
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Bordeaux
Study Sponsor  ICMJE University Hospital, Bordeaux
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University Hospital, Bordeaux
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP