C9orf72 cohort study
A study to characterise C9orf72 patients and asymptomatic carriers
UK Chief Investigator
Professor Kevin Talbot
Research summary
The purpose of this study is to investigate possible causes of nerve damage in patients carrying a genetic abnormality in the gene C9orf72. The abnormality in the C9orf72 gene is known to cause amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), and the related condition frontotemporal dementia (FTD).
To carry out the study, we need to obtain blood and other biological samples from carriers of the C9orf72 gene abnormality who have ALS or FTD, as well as their family members who do not have ALS or FTD symptoms. Identification of why patients carrying the abnormality develop ALS and FTD may help us in the future to find treatments to help prevent these conditions.
The C9orf72 abnormality is the most common genetic cause of ALS and FTD and is present from birth in patients who carry it.
By studying biological samples from patients and relatives, we can gain an understanding of the processes that are at work in this inherited form of ALS and FTD. Samples from blood and the fluid that surrounds the brain as well as brain imaging and electrical nerve tests, provide a window into the changes that are driving the disease at a molecular level. This will help us to increase our understanding of the biological markers that are relevant to the mutation and better monitor response to treatments during future trials.
Eventually, all of this knowledge may contribute towards the development of new treatments for the C9orf72 gene mutation and ALS and FTD in general.
Current status
Active – Recruiting
Key dates
Actual opening date: 5 March 2019
Recruitment planned end date: 30 June 2022
Recruitment groups
Patients with ALS or FTD carrying the C9orf72 HRE (ALS/FTD patients).
Patients with sporadic forms of ALS/FTD.
Family members of patients carrying the C9orf72 HRE who may or may not be aware of their genetic status.
Healthy volunteers with no family history of ALS or FTD.
Recruitment targets
100 ALS/FTD patients
100 family members
50 healthy volunteers
50 patients with sporadic ALS/FTD
Click here to see how many patients have been recruited into this study to date (external link to the NIHR public study search)
Locations
Main site: Oxford
Participant identification centres (invite participants to take part and refer those interested to the main site):
Basingstoke and North Hampshire Hospital
St Mary's Hospital, Isle of Wight NHS Trust
Poole General Hospital
Queen Alexandra Hospital, Portsmouth Hospitals NHS Foundation Trust
Salisbury District Hospital
Western Community Hospital, Solent NHS Trust
Royal Bournemouth General Hospital
Southampton General Hospital
Contact details
Lead site: Emma Harper
Email: emma.harper@ndcn.ox.ac.uk
Inclusion / exclusion criteria
Inclusion criteria
For all participants:
Aged 18 and over.
Participant is willing and able to give informed consent for participation in the study, or an appropriate consultee can be identified to provide advice about his/her friend or relative’s inclusion in the study.
If the participant is unable to provide written consent due to physical disability, an independent witness will be present at the informed consent discussion and sign the consent form on the participant's behalf.
Additional criterion for patients with ALS:
Diagnosis made by experienced neurologist.
Additional criterion for patients with FTD:
Diagnosis made by experienced neurologist or psychiatrist.
Additional criterion for family members:
Known to have C9orf72 HRE mutation, or is a first or second-degree genetic relative of a C9orf72 positive ALS or FTD patient.
Additional criterion for healthy volunteers:
No family history of MND or FTD
Exclusion criteria
The participant may not enter the study if ANY of the following apply:
Under 18 years of age.
Pregnancy or any other condition that in the opinion of the investigator could interfere with the interpretation of the study results.
In addition to the general inclusion / exclusion criteria described above, the additional exclusion criteria apply for invasive procedures (skin biopsy and lumbar puncture):
Significant bleeding diathesis or sepsis, or other condition that in the opinion of the investigator could constitute a health risk to the participant if he/she took part in this element of the study.
In addition to the general inclusion/exclusion criteria described above, the additional exclusion criteria apply for imaging procedures (MRI):
Significant orthopnea or secretions, defined as subjectively intolerable breathlessness on lying flat or oxygen saturations below 90% on lying flat for 10 minutes.
Severe physical disability that might preclude accessing the scanner or prevent communication of any distress during testing or presence of any incompatible (or possibly incompatible) metal implants or large tattoos suspected to contain iron pigments.
In addition to the general inclusion / exclusion criteria described above, the additional exclusion criteria apply for non-invasive EMG:
An implantable cardioverter-defibrillator (ICD) device.
Funders
Association of British Neurologists (ABN) Clinical Research Training Fellowship fund
Motor Neurone Disease Association (MNDA)
Sponsor
University of Oxford
Study design
Cross-sectional observational
Outcome measures
Clinical, biomarker and radiological characterisation of C9orf72 patients and asymptomatic carriers. Clinical database with multi-modal phenotyping data.