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

Study Status: Completed
Recruit Status: Unknown status
Study Type: Observational

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

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.

Detailed Summary:
Sponsor: University Hospital, Bordeaux

Current Primary Outcome: 18F-MPPF binding potential - Biding potential (BP) under placebo in the raphe nucleus [ Time Frame: Second visit (day 1) ]

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


Original Primary Outcome:

Current Secondary Outcome:

  • 18F-MPPF binding potential - Biding potential (BP) in other brain areas [ Time Frame: Second visit (day 1) ]
    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) ]
  • 18F-MPPF binding potential - Biding potential (BP) under placebo in other brain areas [ Time Frame: Third visit (day 30) ]
    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) ]
    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) ]


Original Secondary Outcome:

  • 18F-MPPF binding potential - BP under placebo in other brain areas [ Time Frame: Second (day 1) or third visit (day 30) ]
    Amount of 5-HT1a autoreceptors (evaluated by measurement of 18F-MPPF binding potential - BP) after intake of placebo in other brain areas (brainstem, hyppocampus, etc.).
  • 18F-MPPF binding potential - BP under fluoxetine in all brain areas [ Time Frame: Second (day 1) or third visit (day 30) ]
    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: Second (day 1) and third visit (day 30) ]


Information By: University Hospital, Bordeaux

Dates:
Date Received: May 26, 2010
Date Started: April 2010
Date Completion: December 2015
Last Updated: January 13, 2015
Last Verified: January 2015