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PROgressive Supranuclear Palsy CorTico-Basal Syndrome Multiple System Atrophy Longitudinal Study UK (PROSPECT-M)

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ClinicalTrials.gov Identifier: NCT02778607
Recruitment Status : Recruiting
First Posted : May 20, 2016
Last Update Posted : May 20, 2016
Sponsor:
Collaborators:
University of Cambridge
University of Oxford
University of Manchester
Newcastle University
University of Sussex
Royal Gwent Hospital
Information provided by (Responsible Party):
University College, London

Brief Summary:
Progressive Supranuclear Palsy (PSP), Cortico-Basal Degeneration (CBD) and Multiple System Atrophy (MSA) are degenerative brain conditions for which there are currently no curative treatments. To aid the development of new treatment trials, there is a pressing need to develop better methods for diagnosing these conditions early, and to track disease progression. The PROSPECT-M-UK study will collect standardised clinical data over time. Patients will also have the option to have a brain MRI scan, eye movement exam and donate blood, skin and spinal fluid samples, with the aim to identify "biomarkers" that can improve the accuracy of early diagnosis and track the natural time course of disease. Control participants and those not meeting criteria for Parkinson's disease or other defined conditions but are considered by the investigator group to be allied syndromes or at risk states (atypical parkinsonian syndromes), will also be examined. Patients can also participate via the CBD European registry or in a one-off study assessment through the cross-sectional study, which involves completing questionnaires and a blood sample donation.

Condition or disease
Progressive Supranuclear Palsy (PSP) Corticobasal Degeneration Multiple System Atrophy (MSA)

Detailed Description:

There are a group of neurodegenerative disorders which are often initially diagnosed to be Parkinson's disease (PD), but which are biologically and clinically distinct, and follow a malignant disease course. The three most common conditions are PSP, CBD and MSA. These conditions have a median survival of approximately 6-7 years and unlike PD, do not respond well to dopamine replacement therapy.

PSP and CBD are characterized by tau-pathology and MSA by alpha-synuclein pathology. A great deal of pre-clinical work has been carried out on tau and alpha-synuclein disease models, yet there are no disease modifying agents for these conditions. There are a number of potential therapeutic compounds in development and in order to improve the likelihood of their success, there is a pressing need to increase the number of early case patients recruited into these new treatment trails. Thus, better methods for improved accuracy of early diagnosis and for tracking progression need to be developed. This can be achieved through:

  1. a detailed study of the change in patients' clinical state over time;
  2. studying "biomarkers" such as blood, skin, spinal fluid and brain MRI.

The investigators will recruit patients with PSP, CBD and MSA who are referred to specialist clinics for assessment and treatment. An additional group of Atypical parkinsonian syndrome (APS) cases who do not meet criteria for Parkinson's disease or other defined conditions, but are considered by the investigator group to be allied syndromes or at risk states will also be invited to participate in the study. People unaffected by neurological disease will be invited to participate on a one-off occasion.

Being involved in the PROSPECT-M-UK longitudinal study will involve attending a research assessment on 5 occasions over 3 years; having a neurological examination; completing questionnaires to provide details of clinical history, self/carer reported functional scales and quality of life; neuropsychology assessment; eye movement exam; donating blood and skin samples; some patients will be invited to have a lumbar puncture for spinal fluid collection and have a brain MRI scan on two occasions (at baseline and after 1 year follow-up). Patients can also agree to be contacted by phone or at a clinic appointment on two more occasions at 4 and 5 years.

In addition, a cross-sectional cohort will be established, to enable participation of patients who cannot travel to a study centre. This will involve donating blood samples and returning study questionnaires. A CBD European registry will also be created which will involve a structured neurological assessment, a medical notes review and blood sample donation.

The primary outcome for the study is duration of disease, with the aim to improve methods for early diagnosis and tracking disease progression. Importantly, the study will link together centres and researchers from across Europe to establish the infrastructure and create a trial ready cohort for future therapeutic study into PSP/CBD/MSA.


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Study Type : Observational [Patient Registry]
Estimated Enrollment : 392 participants
Observational Model: Case Control
Time Perspective: Prospective
Target Follow-Up Duration: 5 Years
Official Title: PROgressive Supranuclear Palsy CorTico-Basal Syndrome Multiple System Atrophy Longitudinal Study UK
Study Start Date : October 2014
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021


Group/Cohort
Progressive Supranuclear Palsy
Patients with a current clinical diagnosis of Progressive Supranuclear Palsy (PSP)
Multiple System Atrophy
Patients with current clinical diagnosis of Multiple System Atrophy (MSA).
Atypical Parkinsonian Syndrome
Atypical Parkinsonian Syndrome (APS) patients who do not fulfil existing criteria for PSP/CBD/MSA, but may represent variant clinical syndromes related to tau pathology including pure akinesia with gait freezing (PAGF), PSP-parkinsonism, overlap syndromes and atypical parkinsonian disorders not meeting clinical diagnostic criteria at entry
Controls
Participants unaffected by neurological or psychiatric disease
Corticobasal Degeneration
Patients with a current clinical diagnosis of Corticobasal Degeneration (CBD)



Primary Outcome Measures :
  1. Survival status after 5 years of clinical follow-up [ Time Frame: 5 years ]
    To determine patient survival status after 5 years of follow-up for survival analysis using the Kaplan-Meier Method


Secondary Outcome Measures :
  1. Annual change in degree of disability in PSP, CBD and APS cases as determined by the PSP rating scale [ Time Frame: 3 years ]
    Change in clinical symptoms and motor function in PSP, CBD and APS cases to determine degree of disability and rate of disease progression using a 0-100 rating scale

  2. Annual change in degree of disability in MSA cases as determined by the Unified Multiple System Atrophy Rating Scale (UMSARS) [ Time Frame: 3 years ]
    Change in clinical symptoms and motor function in MSA cases to determine degree of disability and rate of disease progression with scores ranging from 0 to 104


Other Outcome Measures:
  1. CSF biomarkers [ Time Frame: 1 year ]
    Changes in CSF biomarkers of neurodegeneration after one year of follow-up including: neurofilament light chain, total tau, tau isoforms, phosphorylated tau

  2. Brain MRI [ Time Frame: 1 year ]
    Whole and regional brain atrophy (%/year) and functional connectivity measured across distinct brain regions (using low frequency BOLD signal) will be examined after 1 year of follow-up using brain MRI.

  3. MoCA Cognitive function test [ Time Frame: 3 years ]
    Cognitive function will be reviewed annually for 3 years using the Montreal Cognitive Assessment (MoCA). The total score is out of 30 with higher scores indicating better cognitive functioning.

  4. ACE-3 Cognitive function test [ Time Frame: 3 years ]
    Cognitive function will be reviewed annually for 3 years using the Addenbrookes Cognitive Examination (ACE-3). The total score is out of 100 with higher scores indicating better cognitive functioning.

  5. ECAS Cognitive function test [ Time Frame: 3 years ]
    Cognitive function will also viewed annually for 3 years using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). The total score is out of 136 with higher scores indicating better cognitive functioning.


Biospecimen Retention:   Samples With DNA
  1. Blood sample collection for: DNA extraction, Peripheral blood lymphocyte storage, plasma, serum and RNA storage.
  2. Brain MRI scan
  3. Skin biopsy
  4. Cerebro-spinal fluid


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Patient recruitment for the longitudinal study will be through identification of patients by their physicians. The patients will have been referred or will be receiving treatment at a movement disorders, neurology or medical clinic. Patient recruitment for the cross-sectional study will be i.) through identification of patients attending relevant specialist neurology clinics ii.) through information placed on patient organization websites, PSP Association and MSA Trust, and iii.) patients with CBD/CBS can also be recruited via the British Neurological Surveillance Unit (BNSU).
Criteria

Inclusion Criteria:

  • 1. Written informed consent obtained prior to any study-related procedures. A consultee process will be used where participants lack the mental capacity for consent, either due to cognitive or communication deficits.
  • 2. Fulfills clinical criteria (PSP, MSA, CBD/CBS) or clinically defined allied disorders (at-risk states or intermediate disorders, as above) or a healthy control participant recruited from local volunteer databases or next of kin where they have expressed a wish to participate.
  • 3. Participant is 18 years old or older.
  • 4. Participant has an identified informant.

Exclusion Criteria:

  • 1. Participant has another significant medical or psychiatric illness that would interfere in completing assessments
  • 2. Participant is pregnant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02778607


Contacts
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Contact: John Woodside, PhD 020 7679 4272 j.woodside@ucl.ac.uk
Contact: Huw Morris, PhD, FRCP h.morris@ucl.ac.uk

Locations
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United Kingdom
University College London Hospitals Recruiting
London, United Kingdom
Contact: John Woodside, PhD    020 7679 4272    j.woodside@ucl.ac.uk   
Sponsors and Collaborators
University College, London
University of Cambridge
University of Oxford
University of Manchester
Newcastle University
University of Sussex
Royal Gwent Hospital
Investigators
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Principal Investigator: Huw Morris, PhD, FRCP University College, London

Additional Information:

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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT02778607     History of Changes
Other Study ID Numbers: 14/0371
First Posted: May 20, 2016    Key Record Dates
Last Update Posted: May 20, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Following the first 2 years of the study a data and samples access committee will be established comprised of a representative of each study site together with representatives of the PSP Association and MSA trust, and will be chaired by an independent member who is experienced in the review of sample and tissue requests. The availability of tissue and samples will be publicized by the PSP Association and MSA trust.
Keywords provided by University College, London:
Atypical Parkinsonism Syndrome (APS)
Additional relevant MeSH terms:
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Multiple System Atrophy
Shy-Drager Syndrome
Brain Diseases
Supranuclear Palsy, Progressive
Atrophy
Paralysis
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Pathological Conditions, Anatomical
Primary Dysautonomias
Autonomic Nervous System Diseases
Basal Ganglia Diseases
Central Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Hypotension
Vascular Diseases
Cardiovascular Diseases
Ophthalmoplegia
Ocular Motility Disorders
Cranial Nerve Diseases
Tauopathies
Eye Diseases