Multiple System AtrophyASPIRE-MSANCT04229173
Natural History and Disease Progression Biomarkers of Multiple System Atrophy
A study testing MRI acquisition, DAT-SPECT and blood sample, cerebrospinal fluid (optional) in people with Multiple System Atrophy, run by University Hospital, Toulouse at 10 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple System Atrophy
- What is being tested?
- MRI acquisition, DAT-SPECT and blood sample, cerebrospinal fluid (optional)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 10 sitesFrance
- Study dates
- 26 May 2020to 28 Oct 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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)
Show all 19Show fewer
- 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.
- Additional exclusion criteria concerning only patients consenting to the lumbar puncture:
- Coagulopathy and/or anticoagulant treatment
- Thrombocytopenia
- Intracranial hypertension
- Severe degenerative arthritis of the lumbar spine Patients failing to meet these criteria can still participate in the study and all other study assessments (with the exception of lumbar puncture) as appropriate.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
France10 sites
CHU de Bordeaux
Bordeaux, 33076
Hôpital Neurologique Pierre Wertheimer
Bron, 69677
Chu Clermont Ferrand
Clermont-Ferrand, 63003
CHU Lille
Lille, 59037
Hôpital de La Timone
Marseille, 13000
CHU de Nancy
Nancy, 54035
Clinique neurologique - Hôpital Laennec
Nantes, 44093
Hôpital Pitié-Salpêtrière
Paris, 75013
Hôpital de Hautepierre
Strasbourg, 67098
CHU
Toulouse, 31000
About this study
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
Read the detailed description
Surrogate biomarkers are objectively measured characteristics of a disease which act as indicators of the underlying pathophysiological processes responsible for disease progression. Reduced grey matter volume in putamen, cerebellum and brainstem as measured with MRI have been consistently reported to differentiate MSA from other parkinsonian disorders. However, to date, there are no longitudinal studies examining the natural history of MSA on these structural neuroimaging markers over time. The magnitude of the abnormalities observed cross-sectionally in MSA compared to other parkinsonian disorders and the fast clinical progression of the disease make it very likely that structural changes can be observed even over short periods of time. There is also a strong scientific rationale for the potential of measures reflecting white matter integrity, cerebral iron deposition and presynaptic dopaminergic dysfunction, as well as levels of neurofilament light chain (NfL), alpha-synuclein and other proteins involved in the neurodegenerative process in MSA, to serve as progression biomarkers of the disease, although supporting evidence remains limited. A better understanding of the natural history of MSA over 6 and 12 months on a panel of candidate surrogate biomarkers is needed to better understand the disease, help optimise future trial designs in terms of patient selection, sample size and trial duration, and improve the ability to measure the therapeutic effects of novel treatments.
In evaluating potential progression markers of a neurodegenerative disease such as MSA, it is important to control for the normal effects of aging. Studies in healthy volunteers have shown regionally distinct effects of aging on both brain volume and dopamine transporter density, justifying the inclusion of healthy controls with a similar age and gender distribution than patients.
- Conditions
- Multiple System Atrophy
- Being tested
- MRI acquisition, DAT-SPECT, blood sample, cerebrospinal fluid (optional), Evaluations about motor abilities, depression, cognition and lifestyle, Evaluation about depression cognition
- Keywords
- MSA, MRI, Dat spect, Atrophy, Biomarkers
- Medical subject headings
- Multiple System Atrophy, Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI acquisitionDiagnostic test
MRI acquisition
DAT-SPECTDiagnostic test
Imaging with DAT SPECT (Dopamine Transporter, Single Photon Emission Computed Tomography)
blood sample, cerebrospinal fluid (optional)Diagnostic test
blood sample, cerebrospinal fluid
Evaluations about motor abilities, depression, cognition and lifestyleBehavioural
Evaluations about motor abilities (UMSAR scale), depression (BDI scale), cognition (MoCA scale) and lifestyle (MSA- QoL)
Evaluation about depression cognitionBehavioural
Evaluations about depression (BDI scale), cognition (MoCA scale)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Diagnostic Test: MRI acquisition; Behavioral: Evaluation about depression cognition |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: at 12 month
Secondary outcomes (3)
Effect of disease progression on other measures of brain structural integrity and iron accumulation
volume measured with T1-3D MRI, unit : Volume (mm3), Fer: R2* (s-1), diffusion: mean diffusivity (mm2s-1)
Measured: 6 month and 12 month
Effect of disease progression on the loss of presynaptic dopaminergic terminals in the striatum integrity and iron accumulation
volume measured with DAT SPECT (Single Photon Emission Computed Tomography), unit : binding potential (e.g ratio striatum/brain activity)
Measured: 6 month and 12 month
Effect of disease progression on axonal damage as evidenced in biofluids
biomarkers dosages in blood and Cerebral Spinal Fluid total Concentration unit : pg/ml.
Measured: 6 month and 12 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2020
- Study start26 May 2020
- Primary completion30 May 2022
- Study completion28 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple System AtrophyStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olivier RASCOL, MD, PhD, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04229173
- Sponsor's protocol ID
- RC31/19/0161
- Acronym
- ASPIRE-MSA
- Status last verified
- Jun 2023
- First submitted
- 28 Nov 2019
- Last updated
- 22 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History and Disease Progression Biomarkers of Multiple System Atrophy
- ClinicalTrials.gov ID
- NCT04229173
- Acronym / sponsor ID
- ASPIRE-MSA / RC31/19/0161
- Conditions
- Multiple System Atrophy
- Keywords
- MSA, MRI, Dat spect, Atrophy, Biomarkers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 26 May 2020 (actual)
- Primary completion
- 30 May 2022 (actual)
- Study completion
- 28 Oct 2022 (actual)
- First posted
- 18 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Surrogate biomarkers are objectively measured characteristics of a disease which act as indicators of the underlying pathophysiological processes responsible for disease progression. Reduced grey matter volume in putamen, cerebellum and brainstem as measured with MRI have been consistently reported to differentiate MSA from other parkinsonian disorders. However, to date, there are no longitudinal studies examining the natural history of MSA on these structural neuroimaging markers over time. The magnitude of the abnormalities observed cross-sectionally in MSA compared to other parkinsonian disorders and the fast clinical progression of the disease make it very likely that structural changes can be observed even over short periods of time. There is also a strong scientific rationale for the potential of measures reflecting white matter integrity, cerebral iron deposition and presynaptic dopaminergic dysfunction, as well as levels of neurofilament light chain (NfL), alpha-synuclein and other proteins involved in the neurodegenerative process in MSA, to serve as progression biomarkers of the disease, although supporting evidence remains limited. A better understanding of the natural history of MSA over 6 and 12 months on a panel of candidate surrogate biomarkers is needed to better understand the disease, help optimise future trial designs in terms of patient selection, sample size and trial duration, and improve the ability to measure the therapeutic effects of novel treatments.
In evaluating potential progression markers of a neurodegenerative disease such as MSA, it is important to control for the normal effects of aging. Studies in healthy volunteers have shown regionally distinct effects of aging on both brain volume and dopamine transporter density, justifying the inclusion of healthy controls with a similar age and gender distribution than patients.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MSA patients | Other | Diagnostic Test: MRI acquisition, Diagnostic Test: DAT-SPECT, Diagnostic Test: blood sample, cerebrospinal fluid (optional), Behavioral: Evaluations about motor abilities, depression, cognition and lifestylePatients 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 |
| Healthy volunteers | Other | Diagnostic Test: MRI acquisition, Behavioral: Evaluation about depression cognitionhealthy. 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. |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
- Participants with a similar age (+/- 5 years) and gender distribution compared to MSA patients
Key exclusion criteria (19 listed)
- 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)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRI acquisitionMRI acquisition | Diagnostic test | Healthy volunteers, MSA patients |
| DAT-SPECTImaging with DAT SPECT (Dopamine Transporter, Single Photon Emission Computed Tomography) | Diagnostic test | MSA patients |
| blood sample, cerebrospinal fluid (optional)blood sample, cerebrospinal fluid | Diagnostic test | MSA patients |
| Evaluations about motor abilities, depression, cognition and lifestyleEvaluations about motor abilities (UMSAR scale), depression (BDI scale), cognition (MoCA scale) and lifestyle (MSA- QoL) | Behavioural | MSA patients |
| Evaluation about depression cognitionEvaluations about depression (BDI scale), cognition (MoCA scale) | Behavioural | Healthy volunteers |
Primary outcome
Change putamen, cerebellum and brainstem volume measured on MRI
Time frame: at 12 month
volume measured with T1-3D MRI, unit : Volume (mm3), Fer: R2* (s-1), diffusion: mean diffusivity (mm2s-1)
3 secondary outcomes
Effect of disease progression on other measures of brain structural integrity and iron accumulation
Time frame: 6 month and 12 month
Effect of disease progression on the loss of presynaptic dopaminergic terminals in the striatum integrity and iron accumulation
Time frame: 6 month and 12 month
Effect of disease progression on axonal damage as evidenced in biofluids
Time frame: 6 month and 12 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olivier RASCOL, MD, PhD principal investigator
University Hospital, Toulouse
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MRI acquisition, DAT-SPECT and blood sample, cerebrospinal fluid (optional) in people with Multiple System Atrophy, run by University Hospital, Toulouse at 10 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change putamen, cerebellum and brainstem volume measured on MRI (time frame: at 12 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023.