Conectar
Cardiac allograft vasculopathy (CAV) is a critical predictor of the long-term success of heart transplantation and once it is established, progression to graft dysfunction and loss is inevitable, despite adherence to immunosuppression and medications that ameliorate cardiac risk factors. Regulatory T cells (Tregs) are key for maintaining immune balance in the periphery. Studies investigating adoptive transfer of ex vivo expanded Tregs isolated from blood have been shown to be feasible and safe with good evidence for Tregs reducing CAV lesions in animal models of transplantation. Here, we describe the protocol for the ATT-Heart Study which is a phase I clinical trial investigating autologous thymus-derived Treg cell therapy in nine paediatric heart transplant recipients.
Patients will be recruited from the heart transplant waiting list at Great Ormond Street Hospital. Individualised autologous thymus-derived and expanded Tregs (TR006) will be injected into patients 3–6 months after transplant and follow-up will be conducted as per the post-transplant standard of care protocol with no wean of standard of care immunosuppression. Primary endpoint includes occurrence of Dose-limiting Toxicities in patients receiving TR006. Further data from blood tests, endomyocardial biopsy tissue, coronary imaging and clinical follow-up will be collected.
This article is based on the ATT-Heart study Protocol (V.1.1; dated 19 December 2024). The ATT-Heart trial has received a favourable ethical opinion from the Health Research Authority and South-Central Oxford A Research Ethics Committee (IRAS Number: 1008875/REC reference: 24/SC/0333). Clinical trials authorisation approval from UK Medicines and Healthcare products Regulatory Agency has also been received. The clinical trial will be conducted in accordance with the principles of Good Clinical Practice and following the guidelines set as part of the Research Governance Framework for Health and Social Care and all applicable necessary local policies. It is intended that the findings of the clinical trial will be presented at national/international conferences and using social media and through patient groups for dissemination among their members. The results will also be published in international peer-reviewed journals.
Improving the quality of life for preterm children is a global health priority, given their vulnerability to neurocognitive impairments and adverse health consequences. Lack of posthospital care further exacerbates these risks, necessitating effective interventions during the neonatal period. This protocol for a pilot study aims to investigate the effects of touch interventions, including physiotherapy and osteopathic manipulative treatment, on brain activity in moderately preterm infants using brain functional MRI (fMRI), computerised EEG and metabolomics.
A 3-arm randomised sham-controlled trial will be conducted with 15 infants per experimental group. The study will include stable preterm infants born between 32.0 and 33.6 weeks of gestational age who do not require any intensive care treatments.
The study aims to assess the impact of touch interventions on brain activity and metabolic sequelae. Using fMRI will primarily examine the pre-post changes between groups in blood oxygenation level dependent levels among different brain areas, specifically the anterior insula and the medial prefrontal cortex. Secondarily, we will explore the preterm brain’s neural effects on EEG slow delta wave band. Metabolomics will provide data on the effects among the three groups on metabolic changes associated with touch interventions.
Ethical approval has been obtained from the Ethics Committee of the local health agency in Milan (CET 449-2024). Understanding the effects of touch interventions on brain activity in moderately preterm infants, without needs of intensive care, can contribute to improving their clinical outcomes and promoting their growth, development and social behaviour. Findings from this pilot study will pave the way for future research, enabling the development of evidence-based interventions to enhance preterm infants’ well-being and long-term outcomes.
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