Trial designs for delivery of novel therapies for neurodegeneration.
Huntington’s disease (HD) is a brain disorder that is passed down from parent to child. 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.
Cell replacement therapy
One possible way of treating HD (and other brain disease where brain cells are lost) is to replace the cells that die with cells that do not carry the gene mutation, in a procedure called cell replacement therapy (CRT).
Some studies of CRT have been done in people with HD and another brain disorder called Parkinson’s Disease (PD). The treatment was found to be safe, however, because the studies were small, we are not yet sure that this is a reliable long-term treatment for HD.
We led a study of CRT in 5 patients with HD (published in 2002) and although we found it to be safe, the data suggested that we had not put enough cells in the brain to be effective. Therefore, the current study will test the safety and how straightforward it is to put in more cells into the brain.
Between 18 and 30 participants in the early stages of HD will be entered into this study in the Cardiff HD clinic and they will be asked to do some tests to measure their movement and thinking. From these participants, 5 will be randomly chosen to have CRT.
Participant brain scans
Participants will have a brain scan before the transplant, in which 14-22 million foetal cells will be put in one side of the brain during a neurosurgical procedure under general anaesthesia. This is a larger number of cells than has been used in earlier studies.
Because this is a transplant, participants will have to take special drugs to stop their immune system from attacking the new cells. Interviews with the participants will be done before and after the surgery.
Participant follow up
More pictures of the brain will be taken at 3 months and 12 months after the surgery.
Participants will be followed up using a range of tests including regular blood tests and tests of function at 6 and 12 months after surgery, although we will aim to continue following up patients life-long.
We will interview participants who have the transplant surgery before and after they have their 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 participants who were not selected for transplant. We will also interview members of the team working on the trial to understand which the most important parts of the process are. This will help us design ways of measuring how well we run future trials.
Informing future treatment options
The TRIDENT trial (TRIal designs for DElivery of Novel Therapies for neurodegeneration) will also give us information needed to design studies that test how cells, medicines or other therapies can be delivered directly into the brain in patients with neurodegenerative disease.
This is extremely important, as many treatments that could possibly change the course of neurodegenerative disease (such as cells or gene therapies) will need to be put directly into the brain.
Health and Care Research Wales Research for Patient and Public Benefit (RfPPB) Wales
|Start date||1 Oct 2017|
|End date||1 Oct 2019|