Heme-oxygenase-1 in renal transplantation (HOT study)v.1

• Research type

  Research Study

• Full title

  A randomised, placebo controlled trial to study the effect of heme-arginate on heme-oxygenase-1 induction and renal function in recipients of deceased donor renal transplants.

• IRAS ID

  81801

• Contact name

  Rachel Thomas

• Sponsor organisation

  University of Edinburgh

• Eudract number

  2011-004311-23

• Clinicaltrials.gov Identifier

  NCT01430156

• Research summary

  Does pre-treatment of recipients of deceased donor transplants with heme-arginate increase the upregulation of heme-oxygenase-1 protein and subsequently, provide therapeutic benefit? The optimum treatment for patients with end-stage renal disease is renal transplantation. Demand for kidneys outstrips supply and therefore, we are transplanting kidneys that would previously have been rejected, so-called ??extended criteria donor? organs (ECD). During transplantation, the kidney inevitably suffers a damaging interruption to its blood supply, known as ischaemia. The subsequent return of blood flow (reperfusion) is also harmful. This ischaemia-reperfusion injury (IRI) is more destructive to ECD kidneys. IRI is a major cause of delayed graft function (DGF), which is an untreatable, significant cause of transplant failure. Our study will investigate a therapy to optimise the function and survival of transplanted kidneys and hopefully help to increase the number of kidneys available for transplant. We aim to induce heme-oxygenase-1 (HO-1) in recipients of deceased donor transplants. HO-1 is an enzyme that has been shown experimentally to protect kidneys from IRI by catalysing the breakdown of cytotoxic heme.We have funding to run a randomised placebo-controlled clinical trial for 40 patients at the Royal Infirmary in Edinburgh, to investigate the potential efficacy of a drug called heme-arginate (HA). HA has been shown to induce HO-1 in healthy volunteers and has been used safely for over 25 years to treat porphyria. We have used HA to protect against IRI in laboratory experiments but this has never before been studied in humans. Participants will be randomised to receive either HA or placebo (0.9% saline) before their transplant. We will collect participant blood samples and a renal biopsy to determine upregulation of HO-1 and we will monitor the participant's renal function and recovery for 5 days post transplant. Otherwise care will be standard. Recruitment is expected to take 12-18 months.

• REC name

  Scotland A REC

• REC reference

  11/SS/0050

• Date of REC Opinion

  30 Sep 2011

• REC opinion

  Further Information Favourable Opinion