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

Morphological and Functional Investigation of the Serotoninergic System in Multiple System Atrophy: a 18F-MPPF PET Study

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 Overview

• Status: Completed
• Conditions: Multiple System Atrophy
• Intervention / Treatment: Radiation: PET (Positron Emission Tomography) Study; Other: Brain MRI (magnetic resonance imaging); Drug: Fluoxétine / Placebo

• Study Type: Observational
• Enrollment (Actual): 53

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • CHU de Bordeaux
  • Limoges, France
    • CHU Limoges
  • Toulouse, France, 31059
    • CHU de Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited by neurologists specialized in movement disorders

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Idiopathic Parkinson Disease	Radiation: PET (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.; Other: Brain MRI (magnetic resonance imaging); A brain MRI (magnetic resonance imaging)will be performed the day of the first PET study.; Drug: Fluoxétine / 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.
Multiple system atrophy	Radiation: PET (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.; Other: Brain MRI (magnetic resonance imaging); A brain MRI (magnetic resonance imaging)will be performed the day of the first PET study.; Drug: Fluoxétine / 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.
Volunteers without neuropsychiatric disorder (Control)	Radiation: PET (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.; Other: Brain MRI (magnetic resonance imaging); A brain MRI (magnetic resonance imaging)will be performed the day of the first PET study.; Drug: Fluoxétine / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
18F-MPPF binding potential - Biding potential (BP) in other brain areas	Amount of 5-HT1a autoreceptors (evaluated by measurement of 18F-MPPF binding potential) in other brain areas (brainstem, hippocampus, etc.)	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	Amount of 5-HT1a autoreceptors (evaluated by measurement of 18F-MPPF binding potential) after intake of placebo in other brain areas (brainstem, hippocampus, etc.).	Third visit (day 30)
18F-MPPF binding potential - BP under fluoxetine in all brain areas	Amount of 5-HT1a autoreceptors (evaluated by measurement of 18F-MPPF binding potential - BP) after intake of 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)

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Igor SIBON, Pr, University Hospital Bordeaux (France); Study Chair: Geneviève CHENE, Pr, University Hospital Bordeaux (France)

Publications and helpful links

General Publications

• Meyer M, Lamare F, Asselineau J, Foubert-Samier A, Mazere J, Zanotti-Fregonara P, Rizzo G, Delamarre A, Spampinato U, Rascol O, Pavy-Le Traon A, Tison F, Fernandez P, Sibon I, Meissner WG. Brain 5-HT1A Receptor Binding in Multiple System Atrophy: An [18 F]-MPPF PET Study. Mov Disord. 2021 Jan;36(1):246-251. doi: 10.1002/mds.28295. Epub 2020 Sep 21.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2010
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: May 26, 2010
• First Submitted That Met QC Criteria: June 2, 2010
• First Posted (Estimated): June 3, 2010

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Basal Ganglia Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Multiple System Atrophy; Organic Chemicals; Investigative Techniques; Amines; Chemistry Techniques, Analytical; Spectrum Analysis; Propylamines; Fluoxetine; Magnetic Resonance Spectroscopy; 2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole
• Other Study ID Numbers: CHUBX 2008/01; 2008-000485-22 (EudraCT Number)