Transplant research

 

Funding Research in new Transplant Technologies

Transplantation is a successful way to treat people whose own organs stop working but to prevent rejection transplant recipients have to take potent immunosuppressive drugs for the rest of their lives. Appropriate combinations of these drugs can be effective, but this requires life-long administration and results in suppression of the entire immune system non-specifically, including in some cases, the development and function of cells that have the potential to control rejection.

As a result, transplant recipients have an increased risk of cancer and infection, suffer from side-effects associated with the drug therapy and require on-going, intensive clinical management.

Understanding how the immune system is controlled when it responds to a transplant, and promoting the development and function of cells that can prevent rejection selectively hold the key to reducing the unwanted side-effects of immunosuppression.

Oxford Transplant Centres programme of research focuses on how, when and where specialised cells that can control transplant rejection work and what stops them from working.

The key areas that OTC are currently investigating include:

  • Strategies for the induction of tolerance using biological therapeutic agents.
  • The mechanisms of tolerance particularly the role of regulatory T cells and their therapeutic potential.
  • The impact of the immune system on cells and tissues generated from stem cells and tissue scaffolds
  • The translation of laboratory findings to clinical transplantation through the development and validation of biomarkers for monitoring the immune status of transplant recipients
  • Using T cells as a cell therapy for controlling rejection.

The results we obtain will also help develop new treatments for people who have autoimmune diseases, are allergic or have cancer, where controlling the immune system selectively is also critically important.

Kathryn Wood

http://www.nds.ox.ac.uk/research/trig



The Quality in Organ Donation (QUOD) Programme

A bio-resource aiming to improve the quality of donated organs for transplantation

In recent years the transplant community has faced challenges regarding the quality of organs available for transplantation, leading to uncertainty and sometimes discard. QUOD (Quality in Organ Donation) is a National Consortium funded by NHSBT, which started in 2012 and whose aim is to improve the quality of organs by providing biological samples from deceased organ donors for the transplant research community.

QUOD is establishing a central bio-resource of blood, urine and tissues from DBD (Donation after brain death) and DCD (Donation after circulatory death) donors, collected nationally by transplant professionals throughout the organ donation process. All UK retrieval teams are involved in sample collection as well as the SNODs (Specialist Nurses in Organ Donation), who also obtain specific QUOD consent/authorisation from donors’ relatives.

In addition, QUOD has access to comprehensive donor and recipient data from NHSBT which are invaluable for research studies and multivariate analyses. Samples are used to analyse pathways involved in organ injury and repair and to identify novel bio-makers. Interventions performed in the donor and ex-vivo, to allow organ preservation, will be correlated with organ outcomes in the recipient. Biological samples, stored in a central biobank, are accessible to researchers to allow analysis.

www.nds.ox.ac.uk/research/quod

 

COPE Consortium

The COPE Consortium is funded by a European Commission FP7 Award, and is the official organ preservation task force of the European Society for Organ Transplantation (ESOT). The Consortium brings together academic institutions, clinical and scientific experts and SMEs from across Europe to work together on advancing organ preservation techniques and is being led by Professor Rutger Ploeg in Oxford.

The COPE Consortium aims to advance and develop organ preservation technologies by performing clinical and translational studies with on-going experimental refinement. Through testing the quality and safety, increasing the efficiency and refining preservation strategies we aim to bring technologies from the bench to the bedside.

Focusing on four clinical trials across Europe the Consortium will be working on improving preservation and reconditioning strategies for kidney and liver organs procured for transplantation. By exploiting collaborations between industry and academic institutions we aim to introduce organ preservation technologies that will increase the number and quality of grafts used for transplantation.

The four strategic objectives of the programme are:

  1. To test in clinical trials a number of novel clinical approaches to repairing and preserving high-risk donor organs.
  2. To investigate in experimental models a number of novel scientific approaches to organ repair and regeneration.
  3. To develop new objective methods to measure and predict the viability and outcome of donated organs.
  4. To develop an integrated network of academic clinicians and scientists in Europe that, in collaboration with SMEs and ESOT, will develop and implement new medical therapies and devices in organ transplantation.

 

www.nds.ox.ac.uk/research/cope

 

 

Surgical Specialty Lead in Clinical Research – Royal College of Surgeons of England

The Royal College of Surgeons of England is working with partners to develop a nationwide research infrastructure to develop and expand the surgical trials portfolio over the next five years. This programme is being overseen by an independent steering committee.

This initiative seeks to establish at least three centrally funded surgical clinical research centres based within existing clinical trials units of international standing. Speciality based trials development is being supported by surgical specialty leads who have responsibility both for the development of clinical networks to deliver multi-centre studies as well as ensuring that the studies are relevant to their sub-specialty and their patients.

Professor Friend is the Surgical Specialty Lead for Transplantation and the key objectives of his role is to establish two new trials over his first three year tenure, to train up at least one new surgical chief investigator and twenty new principal investigators within transplantation. He will also develop clinical networks that involve both consultants and registrars.

 

 

 

 

 

3C Study

CAMPATH, Calcineurin inhibitor reduction and Chronic allograft nephropathy trial.

The study is called 3C. It aims to test new ways to improve kidney transplants and make them more effective.

Kidney transplantation is a very good treatment for people whose kidneys no longer function sufficiently to keep them alive. Unfortunately, kidney transplant function inevitably declines over time. On average, after about 10 years the transplant “fails” and the recipient either receives another transplant or returns to dialysis.

The aim of 3C is to test two ways to prevent this failure – and help transplant patients now and in the future live longer with better quality of lives. All people who receive a kidney transplant need drugs to prevent their body from “rejecting” the new kidney. Standard medications to prevent rejection may also cause long-term damage to the kidney. The 3C Study is testing two new treatments which might avoid this long-term damage. No one knows which of the two treatments, if any, are better than existing medication.

The treatments being tested relate to immediate treatment after transplant, and long-term care, starting about six months after transplant. The immediate treatment is referred to as ‘induction treatment’ and the longer term care as ‘maintenance treatment’.

We do not know which method of treatments, or combinations of treatment, is best. Patients will be put into different treatment groups, selected by chance (randomly), like the toss of a coin. At the end of the study scientists will analyse which treatment produces the best result. It may be that there is no clear cut answer.

At the time of transplant (‘induction’ treatment)

A patient will be allocated a treatment group at the time of the transplant operation. A computer will decide by chance (like the flicking of a coin) which induction treatment they will receive. This will either be:

  • Standard treatment: basiliximab followed by standard medications. These will include steroids for at least 3 months, after which time they may be stopped if the doctor wishes to do so.
  • New treatment: CAMPATH treatment followed by lower doses of standard medications.
  • Patients treated with CAMPATH will not need steroids.

Six months later (‘maintenance’ treatment)

Once again, the long-term treatment will be chosen at random by a computer. This will either be:

  • Standard maintenance treatment; or
  • New treatment: the patient will be switched to the new drug being tested. This new drug is called sirolimus (Rapamune).

The Principle Investigator for this study is Professor Peter Friend, Professor of Transplantation at the University of Oxford, Consultant Transplant Surgeon and Director of the Oxford Transplant Centre.

Changes in clot structure following kidney-pancreas transplantation

This study is being organised by the Oxford Transplant Centre in collaboration with researchers into blood clotting in Leeds.

It is known that patients with diabetes are at increased risk of developing abnormal blood vessels leading to clots that may cause heart attacks and stroke. These blood clots are abnormal in patients with diabetes, which may be one reason for the increased complications involving blood vessels in diabetics. Previous research suggests that improving diabetes control makes clotting in the blood less likely to happen.

One way to improve blood sugar control is to transplant the pancreas: the organ responsible for controlling blood sugar. We know that having a pancreas transplant can affect clotting of blood for the first few weeks after the operation. However we do not know if the effect on clotting lasts more than a few weeks and affects the risk of heart attacks or strokes in the future.

After a pancreas transplant it is essential to take drugs permanently to prevent the body rejecting the new transplant. These drugs affect the immune system but we do not know if they affect the risk of clotting in the long-term.

The purpose of this study is to investigate the role of improving blood sugar control and commencing anti-rejection drugs on blood clot structure in people with diabetes who have a pancreas transplant. We will be asking people with type 1 diabetes who are due to undergo pancreas transplantation to participate in this study.

ONE Study – Reference Group

After organ transplantation one of the most important problems that can occur is that the body may reject the transplanted organ because of the powerful reaction of the body’s immune system. In order to prevent rejection the patient has to take a number of different drugs for the lifetime of the transplanted organ. These drugs can have side-effects and some patients will still experience rejection episodes in spite of taking the drugs. In recent years we have found out that as well as cells that can damage a transplant, the body makes other cells that control the rejection response. We hope that it may be possible to use these cells grown in the laboratory under very carefully controlled conditions as a new treatment to prevent transplant rejection.

The Reference Group study will involve small volumes of blood and urine being taken at standard clinic visits for extra laboratory tests. 12 weeks following transplantation a sample of kidney tissue (a transplant biopsy) will be taken to look for any signs of transplant rejection.

Chief Investigator is Professor Peter Friend and the Principle Investigator is Dr Paul Harden. This study is being carried out by an EU/USA collaborative group.

BART Study updated May 2015

Biomarker analysis to detect rejection after kidney, pancreas or kidney/pancreas transplant

One of the problems that can occur after someone has a transplant is that the body rejects the graft. In order to prevent this, transplant recipients will have to take several drugs for as long as the transplant is working. All these drugs have side effects which could cause discomfort. Some patients will experience a rejection episode in spite of taking medication to prevent this. It is known that having rejection of the graft can cause damage which can shorten how long the graft lasts.

Results of other studies have shown that it may be possible to detect signs of rejection in the blood of recipients. If this is the case then it would not be necessary to carry out a biopsy. Rejection could be detected by a simple blood test and treated before any damage is done to the graft.

The purpose of this study is to find out if it is possible to detect (or predict) rejection by carrying out detailed tests on the blood of transplant patients before there are any signs, such as a rise in the creatinine levels in the blood and also to look at the genetic make-up of individuals which may affect how the various immunosuppressive drugs are dealt with in the body.

There are differences in the genetic make- up of individuals which may affect how they respond to the drugs needed to prevent rejection of the transplant. By looking at and comparing these variations it may be possible to ensure that immunosuppression is tailored for the individual thus preventing some of the problems arising from using too much or too little immunosuppression.

Up to two sets of blood samples will be taken from kidney donors before the operation. These will be used to compare with the blood of the recipients to see if there are any changes over time that may happen before there are any other signs of graft rejection and to look at the genetic make-up of individuals.

These tests will only be used to detect specific genetic variations which may be related to how the body copes with immunosuppressive drugs and have no clinical significance. They will not be used for any other type of genetic testing.

The Principle Investigator for this study is Professor Peter Friend, Professor of Transplantation at the University of Oxford, Consultant Transplant Surgeon and Director of the Oxford Transplant Centre.

Sentinel Skin Flaps study

One of the main causes of medium term pancreas graft failure is rejection. In many cases we are currently not able to detect rejection early enough to prevent it causing irreversible damage. This is due to a lack of sensitive or specific tests for pancreas graft dysfunction and rejection. We have noticed from our intestinal transplant programme that transplanted skin will often reject before other organs and it is also easily diagnosed by a rash and painless biopsy.

We are setting up a study that will investigate the use of a small donor-derived skin flap that will be transplanted onto the forearm of a patient at the same time as pancreas transplantation. This small patch of skin will then act as a constant visual ‘barometer’ of possible rejection in the pancreas. We hope this will enable much earlier diagnosis and treatment of rejection and thereby significantly improve graft survival for our patients.

Urinary C-peptide study

This study is investigating whether a urine test can help to monitor how well the transplanted pancreas is functioning. It is hoped that this could also be developed into a simple test that could even be sent from home. If we can identify poor pancreas graft function then it may be possible to investigate and treat the causes earlier than is currently possible. This study is a collaboration between the Oxford Transplant Centre, Oxford Centre for Diabetes Endocrinology and Metabolism, and Prof Hattersley’s group at the University of Exeter.

Randomised controlled trial of a GLP-1 drug in pancreas transplantation

Approximately 30% of patients that have a pancreas transplant will experience ‘impaired glucose’ tolerance in the first few weeks after surgery. These patients have a higher chance of the pancreas failing in the medium term and therefore we would like to target these patients with a drug that could potentially help to improve the pancreas function and long term survival. GLP-1 based drugs are currently used in patients with diabetes to help control blood sugar and there is anecdotal evidence that they may help in pancreas and islet transplantation.

We are therefore establishing a trial to study the effects of a GLP-1 drug in our pancreas transplant patients – this will be a multicentre trial run by the surgical trials unit in Oxford but involving all 8 pancreas transplant units in the UK.

Centre for Evidence in Transplantation

The Centre for Evidence in Transplantation (CET) was established by Sir Peter Morris in 2005.  It was based entirely at the Royal College of Surgeons of England initially but also associated with the London School of Hygiene and Tropical Medicine.  However, it now also has a foothold in Oxford and may well move there entirely in due course depending on available space. 

The Centre is devoted to evaluating the quality of evidence in organ transplantation (kidney, heart, lung, pancreas, liver, etc.) and defines gaps in our knowledge in these different areas.  This particularly relates to the use of current immunosuppressant drugs and many of the newer ones have been evaluated over the last ten years.  The Centre produces systematic reviews based in general on randomised control trials, remembering that systematic reviews are Level 1 evidence in the medical field.  Many contributions have been made in kidney, liver and cardiac transplantation by the Research Fellows and Research Associates working in the unit. Doctor Liset Pengel, who started as the first Senior Research Associate in the CET, is now Chief Executive Officer of the Centre and Mr. Simon Knight, who was one of the first Research Fellows and is on the Oxford Training Programme for transplantation, is the Deputy Director.

The Centre has also produced an electronic library of all randomised control trials carried out in organ transplantation and this has been created to  be easy and quick to search.  This is proving extremely popular and for example is taken for all members of the European Society of Organ Transplantation and also or all members of the British Transplant Society.  In addition, the Canadian Transplant Society, the Texas Transplant Society and the Brazilian Transplant Society are amongst some of the other major groups that provide access to the library for their members.  There are also numerous Institutions who also take the Transplant Library as one of their electronic data basis.

The Centre has now also agreed a Centre Network (CETN) which so far involves the Rotterdam Transplant Unit and the Newcastle Unit and negotiations are ongoing with Sydney.  It is expected that the CETN will expand considerably over the next few years.

The CET also produces the Transplant Trial Watch (TTW) which is freely available as an app on both an I-phone and an Android phone. The TTW summarises ten interesting trials in Transplantation that have been added to the Library in the past month.  This is also proving to be a very popular site.

www.nds.ox.ac.uk/research/centre-for-evidence-in-transplantation

 

Transplant Immunology

The Transplant Immunology and Immunogenetics Laboratory provides consultant-lead specialist regional services for clinical transplantation within the Oxford Transplant Centre and for haematopoietic stem cell transplants performed within the OUH. Currently these services include HLA typing to the DNA sequence level, antibody screening and specification and crossmatching.  The laboratory provides a 24-hour on-call service for transplantation and post-transplant monitoring.  Immunogenetics services are also provided to clinicians to define disease susceptibility genes as an aid to patient diagnosis and treatment. The laboratory is accredited by the UK Accreditation Service (UKAS) and the European Federation for Immunogenetics (EFI). Referrals are received from within the OUH and externally from Primary Care Trusts and other Trusts and Institutions.  In order to maintain the highest standards of the services in a continually developing field, the laboratory supports research and development in histocompatibility and immunogenetics testing and in the broader field of clinical transplantation.

|
|
Registered Charity Number 1134241
© Oxford Transplant Foundation 2015 (Last Updated:15/06/2017 )

Home

About OTF

  1. Our Mission
  2. Trustees
  3. Executive Board
  4. Patrons

Research

  1. New technology
  2. Transplant research

Oxford Transplant Centre

  1. About OTC
  2. Consultants
  3. Transplant Nurse Specialists

Patient Info

  1. Transplantation
  2. FAQs
  3. Glossary of terms
  4. Useful links

Support

  1. Ways to support
  2. Fundraising events

Contact

 

Funding Research in new Transplant Technologies

Transplantation is a successful way to treat people whose own organs stop working but to prevent rejection transplant recipients have to take potent immunosuppressive drugs for the rest of their lives. Appropriate combinations of these drugs can be effective, but this requires life-long administration and results in suppression of the entire immune system non-specifically, including in some cases, the development and function of cells that have the potential to control rejection.

As a result, transplant recipients have an increased risk of cancer and infection, suffer from side-effects associated with the drug therapy and require on-going, intensive clinical management.

Understanding how the immune system is controlled when it responds to a transplant, and promoting the development and function of cells that can prevent rejection selectively hold the key to reducing the unwanted side-effects of immunosuppression.

Oxford Transplant Centres programme of research focuses on how, when and where specialised cells that can control transplant rejection work and what stops them from working.

The key areas that OTC are currently investigating include:

  • Strategies for the induction of tolerance using biological therapeutic agents.
  • The mechanisms of tolerance particularly the role of regulatory T cells and their therapeutic potential.
  • The impact of the immune system on cells and tissues generated from stem cells and tissue scaffolds
  • The translation of laboratory findings to clinical transplantation through the development and validation of biomarkers for monitoring the immune status of transplant recipients
  • Using T cells as a cell therapy for controlling rejection.

The results we obtain will also help develop new treatments for people who have autoimmune diseases, are allergic or have cancer, where controlling the immune system selectively is also critically important.

Kathryn Wood

http://www.nds.ox.ac.uk/research/trig



The Quality in Organ Donation (QUOD) Programme

A bio-resource aiming to improve the quality of donated organs for transplantation

In recent years the transplant community has faced challenges regarding the quality of organs available for transplantation, leading to uncertainty and sometimes discard. QUOD (Quality in Organ Donation) is a National Consortium funded by NHSBT, which started in 2012 and whose aim is to improve the quality of organs by providing biological samples from deceased organ donors for the transplant research community.

QUOD is establishing a central bio-resource of blood, urine and tissues from DBD (Donation after brain death) and DCD (Donation after circulatory death) donors, collected nationally by transplant professionals throughout the organ donation process. All UK retrieval teams are involved in sample collection as well as the SNODs (Specialist Nurses in Organ Donation), who also obtain specific QUOD consent/authorisation from donors’ relatives.

In addition, QUOD has access to comprehensive donor and recipient data from NHSBT which are invaluable for research studies and multivariate analyses. Samples are used to analyse pathways involved in organ injury and repair and to identify novel bio-makers. Interventions performed in the donor and ex-vivo, to allow organ preservation, will be correlated with organ outcomes in the recipient. Biological samples, stored in a central biobank, are accessible to researchers to allow analysis.

www.nds.ox.ac.uk/research/quod

 

COPE Consortium

The COPE Consortium is funded by a European Commission FP7 Award, and is the official organ preservation task force of the European Society for Organ Transplantation (ESOT). The Consortium brings together academic institutions, clinical and scientific experts and SMEs from across Europe to work together on advancing organ preservation techniques and is being led by Professor Rutger Ploeg in Oxford.

The COPE Consortium aims to advance and develop organ preservation technologies by performing clinical and translational studies with on-going experimental refinement. Through testing the quality and safety, increasing the efficiency and refining preservation strategies we aim to bring technologies from the bench to the bedside.

Focusing on four clinical trials across Europe the Consortium will be working on improving preservation and reconditioning strategies for kidney and liver organs procured for transplantation. By exploiting collaborations between industry and academic institutions we aim to introduce organ preservation technologies that will increase the number and quality of grafts used for transplantation.

The four strategic objectives of the programme are:

  1. To test in clinical trials a number of novel clinical approaches to repairing and preserving high-risk donor organs.
  2. To investigate in experimental models a number of novel scientific approaches to organ repair and regeneration.
  3. To develop new objective methods to measure and predict the viability and outcome of donated organs.
  4. To develop an integrated network of academic clinicians and scientists in Europe that, in collaboration with SMEs and ESOT, will develop and implement new medical therapies and devices in organ transplantation.

 

www.nds.ox.ac.uk/research/cope

 

 

Surgical Specialty Lead in Clinical Research – Royal College of Surgeons of England

The Royal College of Surgeons of England is working with partners to develop a nationwide research infrastructure to develop and expand the surgical trials portfolio over the next five years. This programme is being overseen by an independent steering committee.

This initiative seeks to establish at least three centrally funded surgical clinical research centres based within existing clinical trials units of international standing. Speciality based trials development is being supported by surgical specialty leads who have responsibility both for the development of clinical networks to deliver multi-centre studies as well as ensuring that the studies are relevant to their sub-specialty and their patients.

Professor Friend is the Surgical Specialty Lead for Transplantation and the key objectives of his role is to establish two new trials over his first three year tenure, to train up at least one new surgical chief investigator and twenty new principal investigators within transplantation. He will also develop clinical networks that involve both consultants and registrars.

 

 

 

 

 

3C Study

CAMPATH, Calcineurin inhibitor reduction and Chronic allograft nephropathy trial.

The study is called 3C. It aims to test new ways to improve kidney transplants and make them more effective.

Kidney transplantation is a very good treatment for people whose kidneys no longer function sufficiently to keep them alive. Unfortunately, kidney transplant function inevitably declines over time. On average, after about 10 years the transplant “fails” and the recipient either receives another transplant or returns to dialysis.

The aim of 3C is to test two ways to prevent this failure – and help transplant patients now and in the future live longer with better quality of lives. All people who receive a kidney transplant need drugs to prevent their body from “rejecting” the new kidney. Standard medications to prevent rejection may also cause long-term damage to the kidney. The 3C Study is testing two new treatments which might avoid this long-term damage. No one knows which of the two treatments, if any, are better than existing medication.

The treatments being tested relate to immediate treatment after transplant, and long-term care, starting about six months after transplant. The immediate treatment is referred to as ‘induction treatment’ and the longer term care as ‘maintenance treatment’.

We do not know which method of treatments, or combinations of treatment, is best. Patients will be put into different treatment groups, selected by chance (randomly), like the toss of a coin. At the end of the study scientists will analyse which treatment produces the best result. It may be that there is no clear cut answer.

At the time of transplant (‘induction’ treatment)

A patient will be allocated a treatment group at the time of the transplant operation. A computer will decide by chance (like the flicking of a coin) which induction treatment they will receive. This will either be:

  • Standard treatment: basiliximab followed by standard medications. These will include steroids for at least 3 months, after which time they may be stopped if the doctor wishes to do so.
  • New treatment: CAMPATH treatment followed by lower doses of standard medications.
  • Patients treated with CAMPATH will not need steroids.

Six months later (‘maintenance’ treatment)

Once again, the long-term treatment will be chosen at random by a computer. This will either be:

  • Standard maintenance treatment; or
  • New treatment: the patient will be switched to the new drug being tested. This new drug is called sirolimus (Rapamune).

The Principle Investigator for this study is Professor Peter Friend, Professor of Transplantation at the University of Oxford, Consultant Transplant Surgeon and Director of the Oxford Transplant Centre.

Changes in clot structure following kidney-pancreas transplantation

This study is being organised by the Oxford Transplant Centre in collaboration with researchers into blood clotting in Leeds.

It is known that patients with diabetes are at increased risk of developing abnormal blood vessels leading to clots that may cause heart attacks and stroke. These blood clots are abnormal in patients with diabetes, which may be one reason for the increased complications involving blood vessels in diabetics. Previous research suggests that improving diabetes control makes clotting in the blood less likely to happen.

One way to improve blood sugar control is to transplant the pancreas: the organ responsible for controlling blood sugar. We know that having a pancreas transplant can affect clotting of blood for the first few weeks after the operation. However we do not know if the effect on clotting lasts more than a few weeks and affects the risk of heart attacks or strokes in the future.

After a pancreas transplant it is essential to take drugs permanently to prevent the body rejecting the new transplant. These drugs affect the immune system but we do not know if they affect the risk of clotting in the long-term.

The purpose of this study is to investigate the role of improving blood sugar control and commencing anti-rejection drugs on blood clot structure in people with diabetes who have a pancreas transplant. We will be asking people with type 1 diabetes who are due to undergo pancreas transplantation to participate in this study.

ONE Study – Reference Group

After organ transplantation one of the most important problems that can occur is that the body may reject the transplanted organ because of the powerful reaction of the body’s immune system. In order to prevent rejection the patient has to take a number of different drugs for the lifetime of the transplanted organ. These drugs can have side-effects and some patients will still experience rejection episodes in spite of taking the drugs. In recent years we have found out that as well as cells that can damage a transplant, the body makes other cells that control the rejection response. We hope that it may be possible to use these cells grown in the laboratory under very carefully controlled conditions as a new treatment to prevent transplant rejection.

The Reference Group study will involve small volumes of blood and urine being taken at standard clinic visits for extra laboratory tests. 12 weeks following transplantation a sample of kidney tissue (a transplant biopsy) will be taken to look for any signs of transplant rejection.

Chief Investigator is Professor Peter Friend and the Principle Investigator is Dr Paul Harden. This study is being carried out by an EU/USA collaborative group.

BART Study updated May 2015

Biomarker analysis to detect rejection after kidney, pancreas or kidney/pancreas transplant

One of the problems that can occur after someone has a transplant is that the body rejects the graft. In order to prevent this, transplant recipients will have to take several drugs for as long as the transplant is working. All these drugs have side effects which could cause discomfort. Some patients will experience a rejection episode in spite of taking medication to prevent this. It is known that having rejection of the graft can cause damage which can shorten how long the graft lasts.

Results of other studies have shown that it may be possible to detect signs of rejection in the blood of recipients. If this is the case then it would not be necessary to carry out a biopsy. Rejection could be detected by a simple blood test and treated before any damage is done to the graft.

The purpose of this study is to find out if it is possible to detect (or predict) rejection by carrying out detailed tests on the blood of transplant patients before there are any signs, such as a rise in the creatinine levels in the blood and also to look at the genetic make-up of individuals which may affect how the various immunosuppressive drugs are dealt with in the body.

There are differences in the genetic make- up of individuals which may affect how they respond to the drugs needed to prevent rejection of the transplant. By looking at and comparing these variations it may be possible to ensure that immunosuppression is tailored for the individual thus preventing some of the problems arising from using too much or too little immunosuppression.

Up to two sets of blood samples will be taken from kidney donors before the operation. These will be used to compare with the blood of the recipients to see if there are any changes over time that may happen before there are any other signs of graft rejection and to look at the genetic make-up of individuals.

These tests will only be used to detect specific genetic variations which may be related to how the body copes with immunosuppressive drugs and have no clinical significance. They will not be used for any other type of genetic testing.

The Principle Investigator for this study is Professor Peter Friend, Professor of Transplantation at the University of Oxford, Consultant Transplant Surgeon and Director of the Oxford Transplant Centre.

Sentinel Skin Flaps study

One of the main causes of medium term pancreas graft failure is rejection. In many cases we are currently not able to detect rejection early enough to prevent it causing irreversible damage. This is due to a lack of sensitive or specific tests for pancreas graft dysfunction and rejection. We have noticed from our intestinal transplant programme that transplanted skin will often reject before other organs and it is also easily diagnosed by a rash and painless biopsy.

We are setting up a study that will investigate the use of a small donor-derived skin flap that will be transplanted onto the forearm of a patient at the same time as pancreas transplantation. This small patch of skin will then act as a constant visual ‘barometer’ of possible rejection in the pancreas. We hope this will enable much earlier diagnosis and treatment of rejection and thereby significantly improve graft survival for our patients.

Urinary C-peptide study

This study is investigating whether a urine test can help to monitor how well the transplanted pancreas is functioning. It is hoped that this could also be developed into a simple test that could even be sent from home. If we can identify poor pancreas graft function then it may be possible to investigate and treat the causes earlier than is currently possible. This study is a collaboration between the Oxford Transplant Centre, Oxford Centre for Diabetes Endocrinology and Metabolism, and Prof Hattersley’s group at the University of Exeter.

Randomised controlled trial of a GLP-1 drug in pancreas transplantation

Approximately 30% of patients that have a pancreas transplant will experience ‘impaired glucose’ tolerance in the first few weeks after surgery. These patients have a higher chance of the pancreas failing in the medium term and therefore we would like to target these patients with a drug that could potentially help to improve the pancreas function and long term survival. GLP-1 based drugs are currently used in patients with diabetes to help control blood sugar and there is anecdotal evidence that they may help in pancreas and islet transplantation.

We are therefore establishing a trial to study the effects of a GLP-1 drug in our pancreas transplant patients – this will be a multicentre trial run by the surgical trials unit in Oxford but involving all 8 pancreas transplant units in the UK.

Centre for Evidence in Transplantation

The Centre for Evidence in Transplantation (CET) was established by Sir Peter Morris in 2005.  It was based entirely at the Royal College of Surgeons of England initially but also associated with the London School of Hygiene and Tropical Medicine.  However, it now also has a foothold in Oxford and may well move there entirely in due course depending on available space. 

The Centre is devoted to evaluating the quality of evidence in organ transplantation (kidney, heart, lung, pancreas, liver, etc.) and defines gaps in our knowledge in these different areas.  This particularly relates to the use of current immunosuppressant drugs and many of the newer ones have been evaluated over the last ten years.  The Centre produces systematic reviews based in general on randomised control trials, remembering that systematic reviews are Level 1 evidence in the medical field.  Many contributions have been made in kidney, liver and cardiac transplantation by the Research Fellows and Research Associates working in the unit. Doctor Liset Pengel, who started as the first Senior Research Associate in the CET, is now Chief Executive Officer of the Centre and Mr. Simon Knight, who was one of the first Research Fellows and is on the Oxford Training Programme for transplantation, is the Deputy Director.

The Centre has also produced an electronic library of all randomised control trials carried out in organ transplantation and this has been created to  be easy and quick to search.  This is proving extremely popular and for example is taken for all members of the European Society of Organ Transplantation and also or all members of the British Transplant Society.  In addition, the Canadian Transplant Society, the Texas Transplant Society and the Brazilian Transplant Society are amongst some of the other major groups that provide access to the library for their members.  There are also numerous Institutions who also take the Transplant Library as one of their electronic data basis.

The Centre has now also agreed a Centre Network (CETN) which so far involves the Rotterdam Transplant Unit and the Newcastle Unit and negotiations are ongoing with Sydney.  It is expected that the CETN will expand considerably over the next few years.

The CET also produces the Transplant Trial Watch (TTW) which is freely available as an app on both an I-phone and an Android phone. The TTW summarises ten interesting trials in Transplantation that have been added to the Library in the past month.  This is also proving to be a very popular site.

www.nds.ox.ac.uk/research/centre-for-evidence-in-transplantation

 

Transplant Immunology

The Transplant Immunology and Immunogenetics Laboratory provides consultant-lead specialist regional services for clinical transplantation within the Oxford Transplant Centre and for haematopoietic stem cell transplants performed within the OUH. Currently these services include HLA typing to the DNA sequence level, antibody screening and specification and crossmatching.  The laboratory provides a 24-hour on-call service for transplantation and post-transplant monitoring.  Immunogenetics services are also provided to clinicians to define disease susceptibility genes as an aid to patient diagnosis and treatment. The laboratory is accredited by the UK Accreditation Service (UKAS) and the European Federation for Immunogenetics (EFI). Referrals are received from within the OUH and externally from Primary Care Trusts and other Trusts and Institutions.  In order to maintain the highest standards of the services in a continually developing field, the laboratory supports research and development in histocompatibility and immunogenetics testing and in the broader field of clinical transplantation.

Raising funds for the sole benefit of the Oxford Transplant Centre....
We need everyone's help. Turn good intentions into action and sign up today by visiting the
Raising funds for the sole benefit of the Oxford Transplant Centre....