Studies Test New Approaches to Islet Transplantation
Researchers from 11 medical centers in the United States,
Canada, Sweden, and Norway have begun testing new approaches to
transplanting clusters of insulin-producing islets in adults with
difficult-to-control type 1 diabetes. The clinical studies,
funded by the National Institutes of Health (NIH), will determine
whether changes to current methods of islet transplantation lead
to improved, long-lasting control of blood glucose with fewer side
effects.
In islet transplantation, clusters of islets are extracted from
a donor pancreas and infused into the recipient's liver. In
a successful transplant, the islets become embedded in the liver
and begin producing insulin.
"A major goal of the NIH research program in type 1 diabetes
is to develop therapies that replace the insulin-producing cells
destroyed by the autoimmune process," said NIH Director Elias
A. Zerhouni, M.D. "These studies, which build on advances
in immunology and transplantation research, may open the door to
more widespread use of islet transplantation for patients with
severe type 1 diabetes."
About 5 percent to 10 percent of the nearly 21 million people
with diabetes have type 1, formerly known as juvenile onset diabetes
or insulin-dependent diabetes. In type 1 diabetes, a person's
own immune cells attack and destroy pancreatic beta cells, which
produce the hormone insulin needed for survival. Beta cells,
along with several other types of cells that work together to balance
blood glucose, reside in islets, also known as islets of Langerhans,
in the pancreas. Three or more insulin injections a
day or treatment with an insulin pump are often needed to maintain
blood glucose control, but most people with type 1 diabetes still
develop complications, including damage to the heart and blood
vessels, eyes, nerves, and kidneys. Despite steady improvements
in managing the disease, type 1 diabetes cuts lives short by about
15 years, with early deaths due mainly to heart attacks and strokes.
In 2000, a research team led by Dr. James Shapiro at the University
of Alberta in Edmonton, Canada, reported sustained insulin independence
in seven patients transplanted with islets from two to four donor
pancreases and treated with an immunosuppressive regimen that omitted
glucocorticoids, thought to be toxic to islets. In the next
few years, other researchers replicated the "Edmonton protocol," and
most centers adopted this approach to islet transplantation.
The protocol greatly benefits some patients with severe type 1
diabetes, but two or more infusions of islets are usually needed,
and the islets tend to lose their insulin-producing function over
time. Participating in an islet transplant study is appropriate
for people with severe hypoglycemia (dangerously low levels
of blood sugar) and for those with type 1 diabetes who have had
a kidney transplant to treat kidney failure, a complication of
diabetes.
Since the Edmonton advance, scientists have been working to lengthen
the survival of donor islets and reduce the side effects — such
as anemia, nerve and kidney damage, and vulnerability to infection — of
drugs that prevent the body's destruction of donor islets. In
the new studies, the researchers will culture islets before transplantation
to enhance their viability. They will also compare specific
anti-rejection drugs for the ability to maximize islet survival
while reducing toxicity. As the procedure becomes safer and new
sources of beta cells become available, more people are likely
to benefit.
The researchers are conducting pilot, or phase 1/2, studies of
experimental agents as well as phase 3 studies that modify the
Edmonton protocol. If the phase 3 studies succeed in safely
controlling blood glucose levels, the investigators may ask the
Food and Drug Administration to approve the procedure for people
with poorly controlled type 1 diabetes. (For information
about the phases of clinical trials, see http://www.fda.gov/fdac/features/2003/503_trial.html.)
"If these approaches are successful in prolonging islet
function with less drug toxicity, type 1 diabetes patients with
severe problems controlling their blood glucose may have another
treatment option for controlling their diabetes," said study
chair Dr. Camillo Ricordi of the University of Miami.
The studies are enrolling individuals with type 1 diabetes who
have serious difficulty controlling their blood glucose despite
intensive medical therapy and who suffer from episodes of severe
hypoglycemia (dangerously low levels of blood glucose). Also
eligible are patients with severe hypoglycemia and hypoglycemia
unawareness, who cannot sense a drop in blood glucose and may lose
consciousness without warning. In addition, researchers are
accepting type 1 diabetes patients who have had a kidney transplant
and are already taking immunosuppressive drugs. For more
information about the studies, call 1-877-IsletStudy (1-877-475-387-8839)
or see http://www.citisletstudy.org/index.html.
The following researchers are conducting the studies:
- Dr. Camillo Ricordi, study chair
University
of Miami
- Dr. Christian Larsen
Emory University,
Atlanta
- Dr. Dixon Kaufman
Northwestern
University, Chicago
- Dr. Bernhard Hering
University
of Minnesota, Minneapolis
- Dr. Ali Naji
University
of Pennsylvania, Philadelphia
- Dr. Peter Stock
University
of California, San Francisco
- Dr. James Shapiro
University
of Alberta, Edmonton, Canada
- Dr. Jose Oberholzer
University
of Illinois at Chicago
- Dr. Aksel Foss
University
Hospital Rikshospitalet, Oslo, Norway
- Dr. Olle Korsgren
Uppsala University
Hospital, Uppsala, Sweden
- Dr. Annika Tibell
Karolinska
University Hospital, Stockholm, Sweden
Dr. William Clarke oversees the Consortium's Data Coordinating
Center at the University of Iowa.
The National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) and the National Institute of Allergy and Infectious Diseases
(NIAID), components of the NIH, are sponsoring the studies. The
studies are funded by a special Congressional funding program for
type 1 diabetes research, recently extended through fiscal year
2009, which supplements the regular NIH appropriation for diabetes
research.
The NIDDK conducts and supports research in diabetes and other
endocrine and metabolic diseases; digestive diseases, nutrition,
and obesity; and kidney, urologic, and hematologic diseases. Spanning
the full spectrum of medicine and afflicting people of all ages
and ethnic groups, these diseases encompass some of the most common,
severe, and disabling conditions affecting Americans. For more
information about NIDDK and its programs, see www.niddk.nih.gov.
NIAID supports basic and applied research to prevent, diagnose
and treat infectious diseases such as HIV/AIDS and other sexually
transmitted infections, influenza, tuberculosis, malaria and illness
from potential agents of bioterrorism. NIAID also supports research
on basic immunology, transplantation and immune-related disorders,
including autoimmune diseases, asthma and allergies. For
more information about NIAID and its programs, see www.niaid.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
|