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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University Hospital, Bordeaux
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01136213
First received: May 26, 2010
Last updated: January 31, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention
Multiple System Atrophy
Radiation: PET (Positron Emission Tomography) Study
Other: Brain MRI (magnetic resonance imaging)
Drug: Fluoxétine / Placebo

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Morphological and Functional Investigation of the Serotoninergic System in Multiple System Atrophy: a 18F-MPPF PET Study

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • 18F-MPPF binding potential - Biding potential (BP) under placebo in the raphe nucleus [ Time Frame: Second visit (day 1) ] [ Designated as safety issue: No ]
    Amount of 5-HT1a autoreceptors (evaluated by measurement of 18F-MPPF binding potential) after intake of placebo in the raphe nucleus.


Secondary Outcome Measures:
  • 18F-MPPF binding potential - Biding potential (BP) in other brain areas [ Time Frame: Second visit (day 1) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Second visit (day 1) ] [ Designated as safety issue: No ]
  • 18F-MPPF binding potential - Biding potential (BP) under placebo in other brain areas [ Time Frame: Third visit (day 30) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Third visit (day 30) ] [ Designated as safety issue: No ]
    Amount of 5-HT1a autoreceptors (evaluated by measurement of 18F-MPPF binding potential - BP) after intake of fluoxetine in all brain areas.

  • Clinical parameters (motor handicap, orthostatic hypotension, quality of life, sleep, pain, tiredness) [ Time Frame: Third visit (day 30) ] [ Designated as safety issue: No ]

Estimated Enrollment: 54
Study Start Date: April 2010
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.
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.
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.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Patients will be recruited by neurologists specialized in movement disorders

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01136213

Contacts
Contact: Igor SIBON, Pr 05 56 79 55 20 igor.sibon@chu-bordeaux.fr
Contact: Sylvain LEDURE 05 56 79 55 20 sylvain.ledure@chu-bordeaux.fr

Locations
France
CHU de Bordeaux Recruiting
Bordeaux, France, 33076
Contact: Igor SIBON, Pr    05 56 79 55 20    igor.sibon@chu-bordeaux.fr   
Sub-Investigator: François TISON, Pr         
Sub-Investigator: Wassilios MEISSNER, Dr         
Sub-Investigator: Michèle ALLARD, Pr         
Sub-Investigator: Olivier FLABEAU, PH         
CHU Limoges Not yet recruiting
Limoges, France
Contact: Philippe COURATIER, PH PU         
Principal Investigator: Philippe COURATIER, Pr         
Sub-Investigator: Frédéric TORNY, Dr         
CHU de Toulouse Recruiting
Toulouse, France, 31059
Contact: Olivier RASCOL, Pr       rascol@cict.fr   
Principal Investigator: Olivier RASCOL, Pr         
Sub-Investigator: Anne PAVY-LE TRAON, Dr         
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Principal Investigator: Igor SIBON, Pr University Hospital Bordeaux (France)
Study Chair: Geneviève CHENE, Pr University Hospital Bordeaux (France)
  More Information

No publications provided

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT01136213     History of Changes
Other Study ID Numbers: CHUBX 2008/01
Study First Received: May 26, 2010
Last Updated: January 31, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Shy-Drager Syndrome
Atrophy
Multiple System Atrophy
Pathological Conditions, Anatomical
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Hypotension
Vascular Diseases
Cardiovascular Diseases
Fluoxetine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 16, 2014