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

May 28, 2021 updated by: University Hospital, Bordeaux

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

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Study Type

Study Type

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Interventional

Enrollment (Anticipated)

Enrollment

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30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

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Study Contact

Study Contact

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Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Molecular imaging
Positron Emission Tomography (PET) molecular imaging of dopaminergic and cholinergic systems using two radiotracers
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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
[18F]-FDOPA SUVr
Time Frame: Between 7 and 30 days after first visit
Standardized uptake value for the [18F]-FDOPA radiotracer
Between 7 and 30 days after first visit
[18F]-FEOBV SUVr
Time Frame: First visit (Day 0)
Standardized uptake value for the [18F]-FEOBV radiotracer
First visit (Day 0)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Apathy Inventory Score
Time Frame: First visit (Day 0)
Apathy score from 0 to 36. Apathetic patient = score >2
First visit (Day 0)
Beck Anxiety Inventory (BAI) Score
Time Frame: First visit (Day 0)
Beck Anxiety Inventory (BAI). Score from . Anxiety = score > 22
First visit (Day 0)
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
First visit (Day 0)
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.
First visit (Day 0)
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
First visit (Day 0)
Fractional anisotropy
Time Frame: First visit (Day 0)
Fractional anisotropy measured with structural MRI
First visit (Day 0)
Mean diffusivity
Time Frame: First visit (Day 0)
Mean diffusivity measured with structural MRI
First visit (Day 0)
Cerebral blood flow maps
Time Frame: First visit (Day 0)
Cerebral blood flow maps provided by arterial spin labeling sequences
First visit (Day 0)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Bordeaux

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 13, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 13, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 13, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 20, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 24, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 26, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 1, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 28, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2021

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CHUBX 2017/22

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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