TRIal designs for DElivery of Novel Therapies for neurodegeneration
Research type
Research Study
Full title
A single site, open label, phase I study to assess the safety and feasibility of foetal stem cell transplants in the striatum of people with Huntington’s Disease.
IRAS ID
231800
Contact name
Chris Shaw
Contact email
Sponsor organisation
Cardiff University
ISRCTN Number
ISRCTN52651778
Duration of Study in the UK
1 years, 9 months, 31 days
Research summary
Research Summary
Huntington’s disease (HD) is a fatal, inherited brain disorder. In HD, cells in a part of the brain called the striatum are slowly lost. This leads to problems with movement, thinking and learning, which get worse over time. At the moment, there are no proven treatments to slow or stop the progression of HD. \nOne possibility for treating HD is to replace the cells that die with cells that do not carry the disease, in an operation called cell transplant therapy (CTT). From a study of CTT in 5 patients with HD we know that is it is safe but that transplanting 11 million foetal cells is not enough to be effective. This study will test the safety of putting more cells into the brain. About 30 participants with HD will be entered into the trial. They will do some tests to measure their movement and thinking. From these participants, about 5 will go on to have CTT. Participants will have brain scans before the transplant, in which 14-22 million foetal cells will be put in one side of the brain under general anaesthetic. Participants will have to take drugs to stop their immune system from attacking new cells. More brain scans will be done at 1 and 12 months after the surgery. Participants will be monitored with regular blood tests and tests of function 6 and 12 months after surgery, although we will continue to follow up participants life-long. We will interview CTT participants before and after they have surgery to ask about their views and understanding of the trial processes and taking part in the trial. We will ask the same questions of participant’s family members/ carers and participants who weren’t selected for CTT. We will also interview research team members to understand what the most important parts of the process are. This will help us design ways of measuring how well we run future trials.\n\n
Summary of Results
Huntington’s Disease (HD) is a rare, inherited disease that causes problems with movement, thinking and behaviour, which get worse over time and eventually lead to death. The genetic cause of the disease leads to the death of cells in the brain known as neurons. There is no cure and there are no medicines that can slow down the progress of the disease. It may be possible to repair the damage to the brain by replacing the neurons lost to the disease with new, unaffected cells. This is known as cell replacement therapy (CRT). We think that adding new cells to the brain will help mend the lost connections and make the problems with movement, thinking and behaviour in HD better. This trial aimed to look at the safety of putting cells into the brains of people with HD. We also wanted to know if the trial design we chose worked well in practice and if the participants taking part in the trial were happy with what they were asked to do.
• It was not possible to transplant foetal cells into the brain of any participant during this trial. This was partly due to suspension of trial activities over the pandemic and partly due to a combination of complex logistical factors made significantly worse by the COVID-19 pandemic.
• Post-pandemic, there were changes to the way in which foetal tissue can be collected locally, which has implications for foetal transplantation moving forward.
• Delivering CRT and other advanced therapies (such as gene therapies) is complex, and would benefit from specialised facilities that offer protected from wider healthcare pressures.
• The Trial Within a Cohort design for investigating CRT in people with HD works well both for the people taking part in the research and the clinicians and researchers running the study.
• The importance of including the patient voice has been highlighted by the interviews we conducted with participants; they are supportive of CRT and supported research in this area.
• Through this trial we have developed a suitable framework for future CRT studies in HD, including all necessary process documentation.REC name
Wales REC 3
REC reference
18/WA/0182
Date of REC Opinion
8 Jun 2018
REC opinion
Further Information Favourable Opinion