NIH Announces New Clinical Trials of Promising Transplant Therapy for Diabetes

NIAID Office of Communications and Public Liaison, GRoa@niaid.nih.gov NIDDK Office of Communications and Public Liaison

Ten research centers will soon begin testing a promising technique for transplanting insulin-producing pancreas cells that may one day allow people with type 1 diabetes to stop their insulin shots. Known as the "Edmonton protocol," the experimental technique is among the first to be carried out in the $144 million Immune Tolerance Network (ITN), an international consortium of clinical researchers dedicated to developing approaches to induce immune "tolerance." If successful, these approaches will selectively modulate the immune system to inhibit harmful immune responses while keeping protective ones intact.

The ITN is a seven-year effort spearheaded by the National Institute of Allergy and Infectious Diseases (NIAID) and co-funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the Juvenile Diabetes Foundation International (JDFI). Both NIAID and NIDDK are components of the U.S. government's National Institutes of Health (NIH).

Starting this fall, the ITN will spend $5 million dollars to expand studies of the Edmonton protocol in centers located in Edmonton, Alberta (Canada), Miami, Minneapolis, Boston, St. Louis, Seattle, and Bethesda, Maryland. Additional European sites are planned in Geneva, Switzerland, Giessen, Germany, and Milan, Italy. Approximately 40 patients-18 to 65 year-olds who have type 1 (juvenile) diabetes and are unable to control their blood sugar with even the most rigid insulin schedule-will receive transplants of the insulin-producing pancreas cells, known as islets, in the next 18 months.

"This trial will serve as a platform for future ITN studies to investigate new 'tolerance therapies,' treatments that may replace the life-long immunosuppressive drugs that transplant recipients currently require to maintain functioning islets," says NIAID Director Dr. Anthony S. Fauci.

The Edmonton protocol was developed by Dr. James Shapiro and colleagues at the University of Alberta. In a journal article last month, Dr. Shapiro and his colleagues reported reversing dependence on insulin injection in seven diabetic patients. The ITN will expand those studies to larger numbers of patients and investigate the underlying immunologic mechanisms at work following islet transplantation.

"While we have known for nearly a decade that tight control of blood glucose delays or prevents diabetes complications, many people have great difficulty achieving optimal control with current treatment methods. Islet transplantation offers the potential for gaining such control and arresting complications," says NIDDK Director Dr. Allen Spiegel.

NIH, which participates in the ITN, will be attempting to duplicate the Edmonton results. Rather than suppressing the body's entire immune system, tolerance therapies specifically block just those immune responses that destroy a person's own tissues or cause them to reject transplanted tissues. Several promising tolerogenic approaches are now under investigation.

"The ITN clinical trials represent a very significant step forward in diabetes research, and we hope to someday make this approach available to all people with diabetes," says Dr. Jeffrey Bluestone, director of the ITN.

Patient Enrollment Criteria and Procedures

Males and females between the ages of 18 to 65 who were diagnosed with type I diabetes at least five years ago and who:

cannot control their blood sugar even with intensive insulin therapy

do not adequately sense the onset of hypoglycemia (low blood sugar)

have had a least one hypoglycemic reaction in the last 1.6 years that cannot be otherwise explained and required medical attention

have secondary complications of diabetes, such as progressive vision, kidney, nerve or vascular problems despite efforts to optimize control of blood sugar

More information for patients wishing to participate is available on the ITN Web site at http://www.immunetolerance.org or from the ITN Patient Referral Hotline at (773) 834-5341 in the United States. Canadian residents may phone (780) 407-1501. Referral forms are to be completed, signed by the patient's physician and returned by January 1, 2001. Patients who appear to meet all the criteria will be contacted for further consultation prior to a final evaluation.

Participating Centers

University of Alberta Clinical Islet Transplantation Program, Edmonton, Alberta, Canada

Diabetes Research Institute, University of Miami, Miami, Florida

Diabetes Institute for Immunology and Transplantation, University of Minnesota, Minneapolis, Minnesota

Juvenile Diabetes Foundation Center for Islet Transplantation, Harvard Medical School, Boston, Massachusetts

Diabetes Research Training Center, Washington University, St. Louis, Missouri

Pacific Northwest Research Institute, Seattle, Washington

Organ/Tissue Transplant Research Center, National Institutes of Health, Bethesda, Maryland

Islet Transplant Centre, Justis-Liebig University, Giessen, Germany

San Raffaele Scientific Institute, University of Milan, Milan, Italy

University Hospital, Geneva, Switzerland

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

The National Institute of Allergy and Infectious Diseases is a component of the National Institutes of Health, U.S. Department of Health and Human Services.