Allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus (interventional procedures consultation)

NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE

Interventional Procedure Consultation Document

Allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus

Type 1 diabetes mellitus occurs when the body does not produce enough insulin (a substance that helps control sugar balance in the body). Although treatable with insulin injections, it is associated with an increased risk of other health problems, such as vascular disease. Allogeneic pancreatic islet cell transplantation involves the removal of islet cells, which are responsible for the production of insulin, from human donors. These cells are inserted into the patient's liver to restart insulin production within the body. Patients who have this procedure take medications so their body's immune system does not reject the cells. It is associated with some serious risks and is only considered in special circumstances.


The National Institute for Health and Clinical Excellence is examining allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. The Institute's Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

  • comments on the preliminary recommendations
  • the identification of factual inaccuracies
  • additional relevant evidence.

Note that this document is not the Institute's formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that the Institute will follow after the consultation period ends is as follows.

  • The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
  • The Advisory Committee will then prepare draft guidance which will be the basis for the Institute's guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.

For further details, see the Interventional Procedures Programme manual, which is available from the Institute's website (www.nice.org.uk/ipprogrammemanual).

NICE is committed to promoting through its guidance race and disability equality and equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our guidance on interventional procedures. In particular, we aim to encourage people and organisations from groups in the population who might not normally comment on our guidance to do so. We also ask consultees to highlight any ways in which draft guidance fails to promote equality or tackle discrimination and how it might be improved.

Closing date for comments: 30 January 2008
Target date for publication of guidance: April 2008


Note that this document is not the Institute's guidance on this procedure. The recommendations are provisional and may change after consultation.


1 Provisional recommendations
1.1 The evidence on allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus shows short-term efficacy with some evidence of long-term efficacy. The evidence on safety shows that serious complications may occur as a result of the procedure. The long-term immunosuppression required is also associated with a risk of adverse events. In units with established experience in allogeneic pancreatic islet cell transplantation, the procedure may be used with normal arrangements for clinical governance (see also section 2.5.2).
1.2 During consent, clinicians should ensure that patients understand the potential complications of the procedure and the uncertainty about its efficacy in the long term. They should provide patients with clear, written information. In addition, use of the Institute's information for patients ('Understanding NICE guidance') is recommended (available from www.nice.org.uk/IPGXXXpublicinfo). [[details to be completed at publication]]
1.3 Patient selection for this procedure should involve a multidisciplinary team. Selection criteria should take into account that the procedure is particularly indicated for patients with hypoglycaemia unawareness and/or those already on immunosuppressive therapy because of renal transplantation.
1.4 Further audit and research should address the effect of the procedure on quality of life and its long-term efficacy particularly in relation to the complications of diabetes (see section 3.1).
     
2 The procedure
2.1 Indications and current treatments
2.1.1 Type 1 diabetes mellitus is characterised by insufficient secretion of insulin. It is associated with increased risk of vascular disease (including retinal, renal and coronary heart disease). The mainstay of treatment is the administration of exogenous insulin but this may result in hypoglycaemic episodes. Such episodes are usually easily recognisable and treatable. However, a small group of patients cannot recognise hypoglycaemia (hypoglycaemia unawareness), which can have life-threatening consequences.
 
2.2 Outline of the procedure
2.2.1 Islet cells are obtained from the pancreases of brain-dead adult donors (often two donors are required). Immunosuppressive therapy is initiated before the procedure and is a long-term requirement. The procedure is performed under local anaesthesia and sometimes with sedation. Using image guidance, a catheter is inserted percutaneously into the portal vein and the isolated islet cells are infused into the liver. More than one infusion may be required. After transplantation, insulin therapy may be reduced or stopped.
 
Sections 2.3 and 2.4 describe efficacy and safety outcomes which were available in the published literature and which the Committee considered as part of the evidence about this procedure. For more details, refer to the sources of evidence (see appendix).    
2.3 Efficacy
2.3.1 A registry study of 112 patients reported that a severe hypoglycaemic episode was experienced by 5% of patients in the year following transplantation compared with 82% in the year prior to transplantation (no numbers provided). In a case series of 36 patients, there were no hypoglycaemic episodes in any of the patients who had residual graft function during follow-up ranging from 1 to 12 months. A case series of 65 patients reported significantly improved scores in hypoglycaemic unawareness and diabetic control compared with baseline for up to 4 years after transplantation (no numbers provided).
2.3.2 In the registry study of 112 patients, 67% achieved insulin independence at 6 months after transplantation and 58% were insulin independent after 1 year (no numbers provided). In patients who remained insulin dependent, insulin requirements were reduced from baseline by a mean of 57% at 6 months and 69% at 1 year. In this study, 13% (15/112) had complete graft failure. In the case series of 36 patients, 58% (21/36) achieved insulin independence during a median follow-up period of 41 months. However, 76% (16/21) of these were insulin dependent again at 2 years.
2.3.3 The Specialist Advisers considered key efficacy outcomes to include insulin independence, improved glycaemic control, reduction in hypoglycaemic episodes and normalised C-peptide levels (indicating graft function).
 
2.4 Safety
2.4.1 Three case series including 65, 51 and 36 patients reported procedure-related intraperitoneal bleeding complications in 23% (15/65) of patients, 8% (4/51) of patients (7 complications total), and 9% (7/77) of infusions, respectively; portal (or branch) vein thrombosis in 8% (5/65), 4% (2/51) and 3% (2/36) of patients, respectively; and gall bladder puncture requiring laparotomy in 3% (2/65) and 3% (1/36) of patients.
2.4.2 In the registry study of 112 patients, 77 serious adverse events were reported; 22% (17/77) were considered life-threatening, 58% (45/77) required hospitalisation and 95% (73/77) resolved without residual effects. Of these events, 27% were judged to be probably or definitely related to immunosuppression; 17% were judged to be probably or definitely related to the infusion procedure (numbers not reported).
2.4.3 A case report described a patient who died because of West Nile virus encephalitis - an infection that can be fatal in any patient treated with immunosuppression.    
2.4.4 The Specialist Advisers considered theoretical adverse events to include haemorrhage, portal vein thrombosis, portal hypertension, complications related to immunosuppression, and transmission of donor material containing infectious agents or neoplastic cells.    
 
2.5 Other comments
2.5.1 The Committee noted that immunosuppressant regimens and the technology for harvesting islet cells both continue to evolve.
2.5.2 The Committee noted that the National Commissioning Group (NCG), which has a remit to commission highly specialised national services for very rare conditions or treatments for the population of England, has developed service standards for pancreatic islet cell transplantation which are used as the basis for designation and commissioning of these services. Scottish residents also have access to the service under an agreement between the NCG and the National Services Division, Scotland. Health Commission Wales has a separate agreement with the provider for Welsh residents. The Regional Medical Services Consortium (RMSC) commissions specialist regional services for the population of Northern Ireland. The RMSC will commission outside the region, on an individual basis, in cases for which services are not available in Northern Ireland.
 
3 Further information
3.1 This guidance requires that clinicians or units undertaking the procedure for the first time make special arrangements for audit. The Institute has identified relevant audit criteria and is developing an audit tool (which is for use at local discretion), which will be available when the guidance is published.
3.2 The Institute has issued a clinical guideline on type 1 diabetes (cg015) and technology appraisals guidance on insulin pump therapy for type 1 diabetes (ta057) and long-acting insulin analogues for type 1 and 2 diabetes (ta053).
   

Bruce Campbell
Chairman, Interventional Procedures Advisory Committee
January 2008

Appendix: Sources of evidence
 

The following document, which summarises the evidence, was considered by the Interventional Procedures Advisory Committee when making its provisional recommendations.

  • 'Interventional procedure overview of allogeneic pancreatic islet cell transplantation for type 1 diabetes mellitus', August 2007.

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