Clinical Studies

Observational (non-drug) clinical projects are studies in which researchers collect different information about research participants but do not administer any kind of treatment or clinical intervention. Observational studies vary in duration and in the type of information they collect.   

Ataxia Centre researchers lead a wide range of clinical studies carried out across UCL-affiliated hospitals, including University College London Hospital (UCLH), National Hospital for Neurology and Neurosurgery at Queen Square.

Current studies

Dentatorubral-pallidoluysian atrophy Natural history and biomarkers Study (DRPLA-NHBS).
Dentatorubral-pallidoluysian atrophy (DRPLA) is a type of inherited autosomal dominant cerebellar ataxia. This condition is characterised by cerebellar ataxia with presence of chorea and cognitive decline, as well as seizures and myoclonus (especially in patients with a younger onset). Ataxia UK and CureDRPLA have funded and established this international project for patients affected with DRPLA and their relatives. The London Ataxia Centre will collaborate with research groups in USA, Japan, Portugal and Italy to enrol participants in this study.

This project has three main objectives. Firstly, we will recruit and follow a group of patients with DRPLA to describe the natural course of the condition (natural history). Having knowledge about how a neurodegenerative condition progresses is fundamental before planning clinical trials, since this information usually helps in calculation of sample size, selection of study variables/methodology, stratification of patients and/or selection of patient subgroups. Secondly, we will study a comprehensive set of biomarkers. A biomarker is a certain characteristic in a subject that can be quantified and that provides information about multiple aspects of a disease. Thus, there are biomarkers that can confirm a certain disease or that can allow the classification of patients in subgroups (diagnostic biomarkers). Others can inform about the probability of developing a certain event in the future (prognostic and progression biomarkers). Finally, some biomarkers can inform about the response to certain interventions (response, monitoring and safety biomarkers). Due to their properties to inform about a disease process and the fact that they can be measured, biomarkers are indispensable tools in clinical trials. We will use different clinical scales and performance tests to rate different symptoms of the condition. We will study genetic biomarker and protein biomarkers in blood, CSF, saliva, urine and faeces. We will also perform brain MRI to identify changes in the appearances of the brain that can reflect the clinical deterioration of the patient. In addition, we will perform neuropsychological tests since patients with DPRLA normally present with problems in cognition (the set of intellectual abilities). We will administer different scales for characterization of the epilepsy in these patients.

Finally, we would like to integrate all this information to try to understand how the condition progresses and which tools will be useful in future collaborative international studies and multicentric clinical trials. 

The recruitment for this study is ongoing. You can register your interest by sending an email to hector.garcia-moreno@nhs.net.

You can read one publication related to this project .

EFACTS - European Friedreich's Ataxia Consortium for Translational Studies

EFACTS is a longitudinal study that will gather vital information to create the largest European FRDA patient database, alongside an integrated clinical and natural history database; this will be linked to a biological samples repository. It also aims to define a panel of clinical assessment tools.
This project proposal has the following scientific and technological objectives:

• Comprehensively populate a European FRDA database, linked to a bio bank
• Define a panel of clinical assessment tools
• Build on the knowledge base of frataxin structure and function
• Build on the knowledge base of the pathogenic cascade
• Build on the knowledge base of epigenetic mechanisms of frataxin silencing
• Develop new cellular and animal models for the study of FRDA
• Identify FRDA biomarkers
• Identify genetic modifiers of FRDA
• Develop therapeutics for FRDA

The recruitment for this study in ongoing. You can read the publications related to this project here. 

ESMI: European Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is the most common autosomal dominant cerebellar ataxia worldwide. Although the gene mutation causing SCA3 is known, there is currently no treatment. However, as there is an advanced understanding of the mechanisms underlying SCA3, new therapeutic approaches are being developed. To enable drug trials, the availability of large cohorts of people who carry the mutation is essential.
ESMI has brought together 8 cohorts comprising more than 800 subjects. Researchers will integrate the existing data in a common database, and apply standardised and qualitycontrolled
assessment protocols. The aims of the study are to:

• Develop disease markers, which will allow for proof-of-concept studies with a biomarker outcome that require smaller numbers of participants than conventional trials
• Bring together existing cohorts to facilitate the enrolment of participants in drug trials.
• Improve data on the long-term evolution of the disease to assist in the design of future clinical trials in SCA3.
• Improve the clinical management of ataxia

In addition to participants diagnosed with SCA3, people with SCA1, SCA2, SCA6, SCA7 and subjects without ataxia can take part in the study as control participants, to have their results compared to the SCA participants. 

The recruitment to this study is ongoing. You can read more information here. 

You can also read the publications linked to this study here:    .

Detecting retinal changes in autosomal recessive spastic of Charlevoix-Saguenay (ARSACS) and other ataxias using optical coherence tomography
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare inherited neurodegenerative disorder first described and most extensively investigated within a small founder population inhabiting the Charlevoix and Saguenay-Lac- St-Jean regions of north-eastern Quebec in Canada. ARSACS has been described in other populations (Japanese, Turkish, Tunisian, Italian, Spanish and British) but the frequency in the UK is currently unknown.
The disorder is characterised by early-onset cerebellar ataxia (incoordination) with spasticity (limb stiffness), peripheral neuropathy (problems with the nerves in the arms and legs), dysarthria (slurred speech) and nystagmus (abnormal eye movements). It has been discovered that a characteristic feature of the Canadian ARSACS cases is a change in the retinal nerve fibre layer at the back of the eye which can be detected by a technique called optical coherence tomography (OCT). This technique is quick, cheap, non-invasive, painless and readily available in most eye clinics. By contrast, the genetic test for ARSACS is expensive and not readily available in most hospitals in this country. The researchers have studied a family with a genetic diagnosis of ARSACS in which some of the unaffected carriers also had changes seen on OCT. It is therefore vital to know whether these retinal changes are a reliable diagnostic indicator amongst the population of people who are routinely assessed in an ataxia clinic. It is important to study patients with ARSACS and the unaffected family members of patients with ARSACS who might be carriers of the gene. They will perform the same test on patients with other (usually genetic) types of ataxia (such as Friedreich’s ataxia or spinocerebellar ataxia) in order to test the sensitivity of OCT in detecting cases of ARSACS. In addition to OCT, the study involves a neurological examination, an MRI scan of the head and neck, and/or a test of memory and thinking called neuropsychometry
The aims of this study are:

• To investigate whether OCT could be used as a screening test to detect people with ARSACS, to decide whether to send for the formal genetic test.
• To better understand the clinical features of people with ARSACS, leading to more accurate diagnosis.
• To study the retinal anatomy of patients with other causes of ataxia using OCT, and to link these to the features seen on routine ophthalmological and neurological examination.

The recruitment to this study is on hold. You can read results published here: 
 

Our role in influencing policy in rare diseases

The Value of Treatment Project 

This study was launched as part of second phase of the Value of Treatment project, initiated by the European Brain Council, focusing on Rare Neurological Diseases. The ataxia case study aims to investigate the value of coordinated care and specialist ataxia centres in delivering early interventions in diagnosis and in management of patients with the ataxias.

This project explores the patient pathways of individuals with progressive ataxias and studies the health economic effects of specialist ataxia centres compared with care in non–specialist settings. The aim is to collect data from the UK, Germany and another European country. The purpose of the survey is to gather information about diagnosis and management of the ataxias in specialist and non-specialist settings. We will also look at the costs and consequences of specialist ataxia centres for the ongoing managing of people diagnosed with ataxia.The London Ataxia Centre is leading this European study. 

This study will provide insight into the value of specialist centres for diagnosis, management of patients with rare conditions, including cost implications. The EBC Value of Treatment project, including several cases studies, aims to influence the policy towards better treatment and care for people with rare neurological diseases across Europe.

You can read the publication linked to this study here: .

Public Policy Projects 

Prof Paola Giunti has taken part in roundtable discussions for the 2022 Rare Disease Program organised by the Public Policy Projects. Several round tables were held with the presence of Stakeholders and Experts to bring their experience and expertise on different topics such as diagnosis; equity of care in clinical development and research; engagement, education and awareness; coordination of care. The programme also hosted a Patient and Advocate Group in parallel which fed into the discussion. This helped keep the voice of the patient at the heart of the disucssions and recommendations which resulted from the series of roundtable. You can find more information here and you can read the report here . 

For any general questions about participation in our clinical research studies please contact our research nurses Dr Shamsher Khan shamsher.khan2@nhs.net or Mrs Katarina Manso katarina.manso@nhs.net

Recent studies

Tracking Progression in Friedreich’s Ataxia (FRDA) to Establish Biomarkers for Clinical Trials.

Friedreich’s ataxia (FRDA) is a devastating neurodegenerative disorder causing loss of balance leading to wheelchair dependence, visual loss, heart failure and diabetes. Clinical trials using promising disease-modifying compounds have not shown a statistically significant improvement suggesting that more reliable markers of disease progression are required. This study aims to investigate quantitative MRI measures in the brain and spinal cord, combined with high resolution imaging of the retina which will be performed over 3 time points, combined with a novel motion detection system. A clinical rating scale known as the SARA score (scale for assessment and rating of ataxia) will be performed to see if it correlates with the retinal imaging and MRI data. This will be the largest study of this kind to date and should assist in clinical trial development. 
The recruitment to this study is now closed. You can read more about this study here: Multimodal Analysis of the Visual Pathways in Friedreich’s Ataxia Reveals Novel Biomarkers. 

Ataxia Patients attitudes to clinical trials

The ataxias are a group of rare neurological disorders characterised by a loss of balance, coordination and speech. As we learn more about these conditions, more clinical trials aiming to test the efficacy and safety of novel therapies are being initiated. Clinical trials often struggle to recruit sufficient participants to either commence the trial or make data obtained reliable. The aim is to survey ataxia patients about trial design preferences in order to make recommendations about how we can improve trial design and thus improve recruitment, participation and the overall trial experience for participants. In this survey we will ask ataxia patients about previous trial experience, ideal length and frequency of visits during the trial, procedures they would be comfortable with, symptoms they would like to be targeted, factors which would increase participation as well as general trial design preferences. The respondents will be members of Ataxia UK and FARA patient support organisations. 

The recruitment for this study is closed. You can read the results here: The attitude of patients with progressive ataxias towards clinical trials. 

The 100,000 Genomes Project 

Link

The 100,000 Genomes Project is a UK Government project that is sequencing whole genomes from National Health Service patients. The project is focusing on rare diseases,
some common types of cancer, and infectious diseases. Participants give consent for their genome data to be linked to information about their medical condition and health
records. The medical and genomic data is shared with researchers, to improve knowledge of the causes, treatment and care of diseases
The aim is to create a new genomic medicine service for the NHS – transforming the way people are cared for. Patients may be offered a diagnosis where there wasn’t one before. In time, there is the potential for new and more effective treatments. The project will also enable new medical research. Combining genomic sequence data with medical records is a ground-breaking resource. Researchers will study how best to use genomics in healthcare and how best to interpret the data to help patients. The causes, diagnosis and treatment of disease will also be investigated. We also aim to kickstart a UK genomics industry. This is currently the largest national sequencing project of its kind in the world.

Recruitment to this study is now closed. You can read about the outcomes of this project here. In particular we had 500 patients from our centre participating, and you can read here the story of one our patients Eileen who got a diagnosis by taking part in this study. This crucial work led to a publication which you can find here tucci8.pdf