Clinical trial NCT01136213: Investigation of the Serotoninergic System in Multiple System Atrophy: a Positron Emission Tomography (PET) Study
Official title: Morphological and Functional Investigation of the Serotoninergic System in Multiple System Atrophy: a 18F-MPPF PET Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple System Atrophy
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2010-06-03
Enrollment: 53
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be recruited by neurologists specialized in movement disorders

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.


Eligibility criteria: 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

Primary outcomes:
measure: 18F-MPPF binding potential - Biding potential (BP) under placebo in the raphe nucleus
timeFrame: Second visit (day 1)
Secondary outcomes:
measure: 18F-MPPF binding potential - Biding potential (BP) in other brain areas
timeFrame: Second visit (day 1)
measure: Clinical parameters (motor handicap, orthostatic hypotension, quality of life, sleep, pain, tiredness)
timeFrame: Second visit (day 1)
measure: 18F-MPPF binding potential - Biding potential (BP) under placebo in other brain areas
timeFrame: Third visit (day 30)
measure: 18F-MPPF binding potential - BP under fluoxetine in all brain areas
timeFrame: Third visit (day 30)
measure: Clinical parameters (motor handicap, orthostatic hypotension, quality of life, sleep, pain, tiredness)
timeFrame: Third visit (day 30)
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Limoges
country: France
facility: CHU Limoges
city: Toulouse
country: France
facility: CHU de Toulouse
Study officials:
affiliation: University Hospital Bordeaux (France)
name: Igor SIBON, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Bordeaux (France)
name: Geneviève CHENE, Pr
role: STUDY_CHAIR
References: