ATT-Heart
Research type
Research Study
Full title
A single ascending dose trial investigating the safety and feasibility of autologous thymus derived regulatory T cell (Tregs) treatment for the prevention of cardiac allograft vasculopathy in children receiving heart transplant.
IRAS ID
1008875
Contact name
Michael Burch
Contact email
Sponsor organisation
Great Ormond Street Hospital for Children NHS Foundation Trust
ISRCTN Number
ISRCTN15374803
Research summary
Heart transplantation is a lifesaving procedure for some children. The long-term success of heart transplants is often limited by inflammatory processes leading to progressive narrowing of blood vessels that supply oxygen to the heart, known as Cardiac Allograft Vasculopathy (CAV).
CAV is a leading cause of death and transplant loss in paediatric cardiac transplantation. Once established, CAV does not respond to conventional medical or surgical approaches, and is one the most important predictors for mortality in this patient population. No effective treatments are available for established CAV. Furthermore, the incidence of CAV in children has not declined over time. Therefore, prevention of CAV (the main cause of graft damage) remains an unmet goal.
Regulatory T cells (Tregs) help maintain the body’s immune system balance and are vital mediators of its immune response. Cell therapy with Tregs shows promise as treatment to generate immune tolerance and improve outcomes for patients in different therapeutic areas. We believe that Treg therapy can prevent CAV in paediatric heart transplant recipients.
The process involves removing the thymus (a gland that sits at the front of the heart and produces T-cells that regulates the body’s immune system) during heart transplantation or at the time of having a pump assist device fitted in, transferring it to a facility for Treg isolation, expansion and cryopreservation for therapeutic administration at 3-6 months post-transplantation.
The expanded Tregs will be injected as treatment to prevent CAV in 9 children receiving heart transplant to test the biological activity of the treatment. Participants will be recruited at Great Ormond Street Hospital and be seen for 3 years during the study.
3 patients will be treated with a low dose of 1-3 x 10^6Tregs/kg and if well tolerated a further 3 will be given a higher dose of 5-10 x 10^6Tregs/kg. An additional 3 patients will be enrolled at the highest tolerated dose.
REC name
South Central - Oxford A Research Ethics Committee
REC reference
24/SC/0333
Date of REC Opinion
17 Dec 2024
REC opinion
Further Information Favourable Opinion