Morphological and Functional Investigation of the Serotoninergic System in Multiple System Atrophy: a 18F-MPPF PET Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 53
- Locations
- 5
- Primary Endpoint
- 18F-MPPF binding potential - Biding potential (BP) under placebo in the raphe nucleus
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Health Services Research
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 30 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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
- •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
- •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
Arms & Interventions
Multiple system atrophy
Intervention: Fluoxétine / Placebo (Drug)
Multiple system atrophy
Intervention: Brain MRI (magnetic resonance imaging) (Other)
Multiple system atrophy
Intervention: PET (Positron Emission Tomography) Study (Radiation)
Volunteers without neuropsychiatric disorder (Control)
Intervention: PET (Positron Emission Tomography) Study (Radiation)
Volunteers without neuropsychiatric disorder (Control)
Intervention: Brain MRI (magnetic resonance imaging) (Other)
Volunteers without neuropsychiatric disorder (Control)
Intervention: Fluoxétine / Placebo (Drug)
Idiopathic Parkinson Disease
Intervention: Fluoxétine / Placebo (Drug)
Idiopathic Parkinson Disease
Intervention: Brain MRI (magnetic resonance imaging) (Other)
Idiopathic Parkinson Disease
Intervention: PET (Positron Emission Tomography) Study (Radiation)
Outcomes
Primary Outcomes
18F-MPPF binding potential - Biding potential (BP) under placebo in the raphe nucleus
Time Frame: 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 Outcomes
- Clinical parameters (motor handicap, orthostatic hypotension, quality of life, sleep, pain, tiredness)(Third visit (day 30))
- 18F-MPPF binding potential - Biding potential (BP) under placebo in other brain areas(Third visit (day 30))
- 18F-MPPF binding potential - Biding potential (BP) in other brain areas(Second visit (day 1))
- 18F-MPPF binding potential - BP under fluoxetine in all brain areas(Third visit (day 30))