Protocol for an open label, phase I trial within a cohort of fetal cell transplants in people with Huntington’s disease

Drew, Cheney ORCID: https://orcid.org/0000-0002-4397-6252, Sharouf, Feras ORCID: https://orcid.org/0000-0002-3034-3392, Randell, Elizabeth, Brookes-Howell, Lucy, Smallman, Kim, Sewell, Bernadette, Burrell, Astrid, Kirby, Nigel, Mills, Laura, Precious, Sophie, Pallmann, Philip ORCID: https://orcid.org/0000-0001-8274-9696, Gillespie, David, Hood, Kerry, Busse, Monica ORCID: https://orcid.org/0000-0002-5331-5909, Gray, William ORCID: https://orcid.org/0000-0001-7595-8887 and Rosser, Anne ORCID: https://orcid.org/0000-0002-4716-4753 2021. Protocol for an open label, phase I trial within a cohort of fetal cell transplants in people with Huntington’s disease. Brain Communications 3 (1) , fcaa230. 10.1093/braincomms/fcaa230

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Abstract

Huntington’s disease is a progressive neurodegenerative disorder characterised by motor, cognitive and psychiatric symptoms. Currently, no disease-modifying therapies are available to slow or halt disease progression. Huntington’s disease is characterised by relatively focal and specific loss of striatal medium spiny neurons, which makes it suitable for cell replacement therapy, a process involving the transplantation of donor cells to replace those lost due to disease. TRIDENT (TRIal DEsigns for delivery of Novel Therapies in neurodegeneration) is a phase I Trial Within a Cohort (TWiC) designed to assess safety and feasibility of transplanting human fetalstriatal cells into the striatum of people with Huntington’s disease. A minimum of 18 participants will be enrolled in the study cohort, and up to five eligible participants will be randomly selected to undergo transplantation of 12-22 million fetal cells in a dose escalation paradigm. Independent reviewers will assess safety outcomes (lack of significant infection, bleeding or new neurological deficit) four weeks after surgery, and ongoing safety will be established before conducting each subsequent surgery. All participants will undergo detailed clinical and functional assessment at baseline, 6 and 12 months. Surgery will be performed one month after baseline, and transplant participants will undergo regular clinical follow-up for at least 12 months. Evaluation of trial processes will also be undertaken. Transplant participants and their carers will be interviewed approximately one month before and after surgery. Interviews will also be conducted with non-transplanted participants and healthcare staff delivering the intervention and involved in the clinical care of participants. Evaluation of clinical and functional efficacy outcomes and intervention costs will be carried out to explore plausible trial designs for subsequent randomised controlled trials aimed at evaluating efficacy and cost-effectiveness of cell replacement therapy. TRIDENT will enable the assessment of the safety, feasibility, acceptability and cost of fetalcell transplants in people with Huntington’s disease. The data collected will inform trial designs for complex intracranial interventions in a range of neurodegenerative conditions and facilitate the development of stable surgical pipelines for delivery of future stem cell trials.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information:	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/
Publisher:	Oxford University Press
ISSN:	2632-1297
Date of First Compliant Deposit:	6 January 2021
Date of Acceptance:	30 October 2020
Last Modified:	08 Nov 2024 03:15
URI:	https://orca.cardiff.ac.uk/id/eprint/137280

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