Natural History and Disease Progression Biomarkers of Multiple System Atrophy

NCT04229173 | Completed DMC

• 1 other identifier: RC31/19/0161
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 10

Brief Summary

Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disease characterised by a variable combination of parkinsonism, cerebellar impairment and autonomic dysfunction. The neuropathological hallmark is the accumulation of alpha-synuclein in oligodendrocytes. While some symptomatic treatments exist, neuroprotective treatments for MSA remain an urgent, unmet need. Moreover, at present there is not a single surrogate biomarker of MSA which could be used to inform clinical trials. This study seeks to characterise the natural history of MSA on a panel of candidate biomarkers, pre-selected for being putative surrogates of the underlying neurodegenerative process

Conditions

Multiple System Atrophy

Keywords

MSA; MRI; Dat spect; Atrophy; Biomarkers

Outcome Measures

Primary Outcomes (1)

• Change putamen, cerebellum and brainstem volume measured on MRI

  volume measured with T1-3D MRI, unit : Volume (mm3), Fer: R2\* (s-1), diffusion: mean diffusivity (mm2s-1)

  at 12 month

Secondary Outcomes (3)

• Effect of disease progression on other measures of brain structural integrity and iron accumulation

  6 month and 12 month

• Effect of disease progression on the loss of presynaptic dopaminergic terminals in the striatum integrity and iron accumulation

  6 month and 12 month

• Effect of disease progression on axonal damage as evidenced in biofluids

  6 month and 12 month

Study Arms (2)

MSA patients

OTHER

Patients with multiple system atrophy will be examined at baseline, 6 months and 12 months via the following procedures performed at all 3 visits: * a clinical examination; * blood and cerebrospinal fluid (CSF) (optional) sampling for the assessment of selected fluid biomarkers; * MRI for the assessment of brain volume, white matter integrity and cerebral iron deposition; DAT-SPECT (Dopamine Transporter, Single Photon Emission Computed Tomography) for the assessment of presynaptic dopaminergic function

Diagnostic Test: MRI acquisition; Diagnostic Test: DAT-SPECT; Diagnostic Test: blood sample, cerebrospinal fluid (optional); Behavioral: Evaluations about motor abilities, depression, cognition and lifestyle

Healthy volunteers

OTHER

healthy. Controls will undergo an MRI scan at baseline, 6 months and 12 months, and a DAT-SPECT(Dopamine Transporter, Single Photon Emission Computed Tomography) scan at baseline and 12 months.

Diagnostic Test: MRI acquisition; Behavioral: Evaluation about depression cognition

Interventions

MRI acquisition DIAGNOSTIC_TEST

MRI acquisition

Healthy volunteers; MSA patients

DAT-SPECT DIAGNOSTIC_TEST

Imaging with DAT SPECT (Dopamine Transporter, Single Photon Emission Computed Tomography)

MSA patients

blood sample, cerebrospinal fluid (optional) DIAGNOSTIC_TEST

blood sample, cerebrospinal fluid

MSA patients

Evaluations about motor abilities, depression, cognition and lifestyle BEHAVIORAL

Evaluations about motor abilities (UMSAR scale), depression (BDI scale), cognition (MoCA scale) and lifestyle (MSA- QoL)

MSA patients

Evaluation about depression cognition BEHAVIORAL

Evaluations about depression (BDI scale), cognition (MoCA scale)

Healthy volunteers

Eligibility Criteria

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

You may qualify if:

• Applicable to MSA patients:
• Patients with possible or probable MSA according to consensus diagnosis criteria \[Gilman et al., 2008\]
• Patients aged between 30 and 80 years
• Patients at the early stages of the disease, defined as maximum 5 years since the onset of one of the following symptoms associated to MSA:
• Parkinsonism Ataxia Orthostatic hypotension and/or urinary dysfunction - Patients with an anticipated survival of at least 3 years on the basis of Investigators' clinical judgment
• Applicable to healthy controls:
• Participants with a similar age (+/- 5 years) and gender distribution compared to MSA patients
• Participants with absence of neurological pathology
• Patients aged between 25 and \< 80 years
• Applicable to both patients and healthy controls:
• \- Participants who voluntarily sign the written informed consent form, indicating that they understand the purpose of and procedures required for the study and are willing to participate in it Participants affiliated to the French social security health system

You may not qualify if:

• Applicable to MSA patients:
• Speech impairment (score of ≥3 on UMSARS (Unified Multiple System Atrophy Rating Scale) question 1);
• Impairment in ambulation (score of ≥3 on UMSARS (Unified Multiple System Atrophy Rating Scale) question 7)
• Falling more frequently than once per week (score of ≥3 on UMSARS (Unified Multiple System Atrophy Rating Scale) question 8)
• Applicable to both MSA patients and healthy controls:
• Participants with significant cognitive impairment (MoCA score \<21)
• Any major medical or psychiatric condition which may compromise participation in the study or the safety, at the discretion of the Investigator
• Contraindications for MRI imaging, including claustrophobia and presence of metallic implants such as cardiac or auditory prostheses, pacemakers or cerebral clips
• Contraindications to obtain a FP-CIT SPECT(Single Photon Emission Computed Tomography) (i.e. known hypersensitivity to the active substance or to any of the excipients, or to iodine)
• Current pharmacological treatments that may alter the DAT(dopamine transporter ) SPECT (Single Photon Emission Computed Tomography) reading, including amphetamines, benzatropine, buproprion (amfebutamone), cocaine, mazindol, methylphenidate, phentermine or sertraline
• Females who are pregnant, breast feeding or of child bearing age without effective contraception
• Participants who lack the capacity to give informed consent
• Participants taking any investigational products within 3 months before baseline assessment
• Participant under adult autonomy protection system, legal guardianship or incapacitation.
• Coagulopathy and/or anticoagulant treatment

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (10)

CHU de Bordeaux

Bordeaux, 33076, France

Location

Hôpital Neurologique Pierre Wertheimer

Bron, 69677, France

Location

Chu Clermont Ferrand

Clermont-Ferrand, 63003, France

Location

CHU Lille

Lille, 59037, France

Location

Hôpital de La Timone

Marseille, 13000, France

Location

CHU de Nancy

Nancy, 54035, France

Location

Clinique neurologique - Hôpital Laennec

Nantes, 44093, France

Location

Hôpital Pitié-Salpêtrière

Paris, 75013, France

Location

Hôpital de Hautepierre

Strasbourg, 67098, France

Location

CHU

Toulouse, 31000, France

Location

MeSH Terms

Conditions

Multiple System Atrophy; Atrophy

Interventions

Blood Specimen Collection

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; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Olivier RASCOL, MD, PhD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2019
• First Posted: January 18, 2020
• Study Start: May 26, 2020
• Primary Completion: May 30, 2022
• Study Completion: October 28, 2022
• Last Updated: June 22, 2023

Record last verified: 2023-06

Locations

FR (10)