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

Multiple System Atrophy Clinical Trial

— SEROTAMS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01136213
• Other study ID #: CHUBX 2008/01
• Status: Completed
• Phase: N/A
• First received: May 26, 2010
• Last updated: August 3, 2017
• Start date: April 2010
• Est. completion date: March 2016

Study information

• Verified date: August 2017
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Atrophy
• Multiple System Atrophy
• Shy-Drager Syndrome

Intervention

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.

Locations

Country	Name	City	State
France	CHU de Bordeaux	Bordeaux
France	CHU Limoges	Limoges
France	CHU de Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	Clinical parameters (motor handicap, orthostatic hypotension, quality of life, sleep, pain, tiredness)		Second visit (day 1)
Secondary	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)
Secondary	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)
Secondary	Clinical parameters (motor handicap, orthostatic hypotension, quality of life, sleep, pain, tiredness)		Third visit (day 30)