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Trial record 27 of 90 for:    "Brain Diseases" AND "Multiple System Atrophy"

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

Tracking Information
First Submitted Date April 22, 2016
First Posted Date May 20, 2016
Last Update Posted Date May 20, 2016
Study Start Date October 2014
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 17, 2016)
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
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: May 17, 2016)
  • 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
  • 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
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 17, 2016)
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title PROgressive Supranuclear Palsy CorTico-Basal Syndrome Multiple System Atrophy Longitudinal Study UK
Official Title PROgressive Supranuclear Palsy CorTico-Basal Syndrome Multiple System Atrophy Longitudinal Study UK
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.
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.

Study Type Observational [Patient Registry]
Study Design Observational Model: Case Control
Time Perspective: Prospective
Target Follow-Up Duration 5 Years
Biospecimen Retention:   Samples With DNA
Description:
  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
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).
Condition
  • Progressive Supranuclear Palsy (PSP)
  • Corticobasal Degeneration
  • Multiple System Atrophy (MSA)
Intervention Not Provided
Study Groups/Cohorts
  • 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)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: May 17, 2016)
392
Original Estimated Enrollment Same as current
Estimated Study Completion Date October 2021
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility 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.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts
Contact: John Woodside, PhD 020 7679 4272 j.woodside@ucl.ac.uk
Contact: Huw Morris, PhD, FRCP h.morris@ucl.ac.uk
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT02778607
Other Study ID Numbers 14/0371
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
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.
Responsible Party University College, London
Study Sponsor University College, London
Collaborators
  • University of Cambridge
  • University of Oxford
  • University of Manchester
  • Newcastle University
  • University of Sussex
  • Royal Gwent Hospital
Investigators
Principal Investigator: Huw Morris, PhD, FRCP University College, London
PRS Account University College, London
Verification Date April 2016