PROgressive Supranuclear Palsy CorTico-Basal Syndrome Multiple System Atrophy Longitudinal Study UK (PROSPECT-M)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02778607|
Recruitment Status : Recruiting
First Posted : May 20, 2016
Last Update Posted : May 20, 2016
|Condition or disease|
|Progressive Supranuclear Palsy (PSP) Corticobasal Degeneration Multiple System Atrophy (MSA)|
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:
- a detailed study of the change in patients' clinical state over time;
- 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]|
|Estimated Enrollment :||392 participants|
|Observational Model:||Case Control|
|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|
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
Participants unaffected by neurological or psychiatric disease
Patients with a current clinical diagnosis of Corticobasal Degeneration (CBD)
- 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
- 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
- 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.
Biospecimen Retention: Samples With DNA
- Blood sample collection for: DNA extraction, Peripheral blood lymphocyte storage, plasma, serum and RNA storage.
- Brain MRI scan
- Skin biopsy
- Cerebro-spinal fluid
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
|Contact: John Woodside, PhD||020 7679 email@example.com|
|Contact: Huw Morris, PhD, FRCPfirstname.lastname@example.org|
|University College London Hospitals||Recruiting|
|London, United Kingdom|
|Contact: John Woodside, PhD 020 7679 4272 email@example.com|
|Principal Investigator:||Huw Morris, PhD, FRCP||University College, London|