Multiple System Atrophy
Conditions
Brief summary
Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder of the adult associated to a poor prognosis. MSA is clinically characterized by the association of extra-pyramidal, dysautonomic, cerebellar and pyramidal symptoms. Histological and biological studies have raised the hypothesis that, beside the well known dopamine deficiency, some of the symptoms could be related to a dysfunction in serotoninergic neurotransmission. Serotonin is involved in the modulation of several functions impaired in MSA, such as mood, motricity or sleep. The recent description of an association between loss of brainstem serotonin neurons and sudden death in patients with MSA reinforced the hypothesis of a critical role played by this neurotransmitter in the pathophysiology of this disease. Autoreceptors called 5-HT1a are strongly involved in the regulation of serotonin neurotransmission. During the last years several radio-ligands allowing in vivo PET quantification of 5-HT1a receptors, such as 18F-MPPF (4-(2'-methoxyphenyl)-1-\[2'-(N-2''-piridinyl)-p-fluorobenzamide\]methylpiperazine), were developed. Moreover, the investigators recently demonstrated the ability of this brain functional imaging method to investigate, in healthy volunteers, the functional properties of 5-HT1a autoreceptors through an evaluation of their desensitization after a single oral dose of fluoxetine.
Interventions
RADIATIONPET (Positron Emission Tomography) Study
5-HT1a auto-receptors will be visualized in vivo using 18F-MPPF PET study. Two PET studies will be performed, one after the intake of a single oral dose of fluoxetine and the other after placebo. The order of fluoxetine and placebo intake will be randomly assigned.
OTHERBrain MRI (magnetic resonance imaging)
A brain MRI (magnetic resonance imaging)will be performed the day of the first PET study.
DRUGFluoxétine / Placebo
The two PET studies will be performed, one after the intake of a single oral dose of fluoxetine and the other after placebo. The order of fluoxetine and placebo intake will be randomly assigned.
Sponsors
University Hospital, Bordeaux
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Patients with Multiple system atrophy (MSA) * MSA possible or probable * Male and female * Age : 30 to 80 * No cognitive impairment * Unmodified treatment for 2 months * Able to give informed consent * Affiliated to social insurance * Patients with idiopathic Parkinson's disease (IPD): * Positive clinical criteria for IPD * Male and female * Age : 30 to 80 * No cognitive impairment * Unmodified treatment for 2 months * Able to give informed consent * Affiliated to social insurance * Healthy controls: * Absence of neuropsychiatric disorder * Male and female * Age : 30 to 80 * Able to give informed consent * Affiliated to social insurance
Exclusion criteria
* Patients with Multiple system atrophy (MSA) * Other Parkinsonian syndrome * Dementia * Recent intake (\< 4 weeks or 8 weeks for fluoxetine) of medication acting on 5-HT1a receptors * History of major depression * Contraindication to brain MRI * Contraindication to PET * Patients with idiopathic Parkinson's disease * Other Parkinsonian syndrome * Dementia * Recent intake (\< 4 weeks or 8 weeks for fluoxetine) of medication acting on 5-HT1a receptors * History of major depression * Contraindication to brain MRI * Contraindication to PET * Healthy controls: * Patient having a neuropsychiatric disease * Recent intake (\< 4 weeks or 8 weeks for fluoxetine) of medication acting on 5-HT1a receptors * History of major depression * Contraindication to brain MRI * Contraindication to PET
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 18F-MPPF binding potential - Biding potential (BP) under placebo in the raphe nucleus | Second visit (day 1) | Amount of 5-HT1a autoreceptors (evaluated by measurement of 18F-MPPF binding potential) after intake of placebo in the raphe nucleus. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 18F-MPPF binding potential - Biding potential (BP) in other brain areas | Second visit (day 1) | Amount of 5-HT1a autoreceptors (evaluated by measurement of 18F-MPPF binding potential) in other brain areas (brainstem, hippocampus, etc.) |
| Clinical parameters (motor handicap, orthostatic hypotension, quality of life, sleep, pain, tiredness) | Second visit (day 1) | — |
| 18F-MPPF binding potential - Biding potential (BP) under placebo in other brain areas | Third visit (day 30) | Amount of 5-HT1a autoreceptors (evaluated by measurement of 18F-MPPF binding potential) after intake of placebo in other brain areas (brainstem, hippocampus, etc.). |
| 18F-MPPF binding potential - BP under fluoxetine in all brain areas | Third visit (day 30) | Amount of 5-HT1a autoreceptors (evaluated by measurement of 18F-MPPF binding potential - BP) after intake of fluoxetine in all brain areas. |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORIgor SIBON, Pr
University Hospital Bordeaux (France)
STUDY_CHAIRGeneviève CHENE, Pr
University Hospital Bordeaux (France)
Outcome results
None listed