Investigation of the Serotoninergic System in Multiple System Atrophy: a Positron Emission Tomography (PET) Study

NCT01136213 | Completed

• 1 other identifier: CHUBX 2008/01
• Study Type: observational
• Target: 53
• Locations: 1 country
• Sites: 3

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.

Conditions

Multiple System Atrophy

Outcome Measures

Primary Outcomes (1)

• 18F-MPPF binding potential - Biding potential (BP) under placebo in the raphe nucleus

  Amount of 5-HT1a autoreceptors (evaluated by measurement of 18F-MPPF binding potential) after intake of placebo in the raphe nucleus.

  Second visit (day 1)

Secondary Outcomes (5)

• 18F-MPPF binding potential - Biding potential (BP) in other brain areas

  Second visit (day 1)

• 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)

• 18F-MPPF binding potential - BP under fluoxetine in all brain areas

  Third visit (day 30)

• Clinical parameters (motor handicap, orthostatic hypotension, quality of life, sleep, pain, tiredness)

  Third visit (day 30)

Study Arms (3)

Multiple system atrophy

Radiation: PET (Positron Emission Tomography) Study; Other: Brain MRI (magnetic resonance imaging); Drug: Fluoxétine / Placebo

Idiopathic Parkinson Disease

Radiation: PET (Positron Emission Tomography) Study; Other: Brain MRI (magnetic resonance imaging); Drug: Fluoxétine / Placebo

Volunteers without neuropsychiatric disorder (Control)

Radiation: PET (Positron Emission Tomography) Study; Other: Brain MRI (magnetic resonance imaging); Drug: Fluoxétine / Placebo

Interventions

PET (Positron Emission Tomography) Study RADIATION

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.

Idiopathic Parkinson Disease; Multiple system atrophy; Volunteers without neuropsychiatric disorder (Control)

Brain MRI (magnetic resonance imaging) OTHER

A brain MRI (magnetic resonance imaging)will be performed the day of the first PET study.

Idiopathic Parkinson Disease; Multiple system atrophy; Volunteers without neuropsychiatric disorder (Control)

Fluoxétine / Placebo DRUG

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.

Idiopathic Parkinson Disease; Multiple system atrophy; Volunteers without neuropsychiatric disorder (Control)

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited by neurologists specialized in movement disorders

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (3)

CHU de Bordeaux

Bordeaux, 33076, France

Location

CHU Limoges

Limoges, France

Location

CHU de Toulouse

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Multiple System Atrophy

Interventions

2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole; Magnetic Resonance Spectroscopy; Fluoxetine

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Propylamines; Amines; Organic Chemicals

Study Officials

• Igor SIBON, Pr

  University Hospital Bordeaux (France)

  PRINCIPAL INVESTIGATOR

• Geneviève CHENE, Pr

  University Hospital Bordeaux (France)

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2010
• First Posted: June 3, 2010
• Study Start: April 1, 2010
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: August 4, 2017

Record last verified: 2017-08

Locations

FR (3)