To Sandy & Calvin
-Here is a page about the trials of what is called "The Edmonton
Protocol" for beta cell transplantation, developed by Dr. Shapiro in
Edmonton, Cananda…I first read about this a couple years ago when a
friend brought me a copy of the "Saturday Evening Post" magazine,
October, maybe, 2001, which had an extensive article about it. I was
still a non-computer person at the time, so I hand wrote a letter to
this organization (Immune Tolerance Network), asking to participate
(me and probably everybody else in the world with type-1
diabetes!)….Nothing came of it. I guess the current trials have
enough people in them. At least you can learn something about it on
this site (web address near the end)…Also, they mention a new
round of trials near the end…There may be other ways or places to
get involved…The U of Minnesota, Minneapolis has a very active
research/transplantation program…I don’t know what part of the
world you live in…I will keep looking. -Linda R PS I marked the
parts I mentioned above with *****’s and !!!!’s to make them easier
to find.
****************************************************************
Jun 2, 2003
Preliminary Results of ITN Multicenter Islet Transplant Trial Confirm
Potential Patient Benefits, Underscore Steep Learning Curve
The Immune Tolerance Network (ITN) today announced preliminary
results from its 36-patient multicenter clinical trial of the
Edmonton Protocol for islet transplantation, confirming in an early
analysis that the treatment for type 1 diabetes pioneered in
Edmonton, Canada, can be successfully replicated at other clinical
sites.
Of the 15 patients able to complete their transplants, 12 (80%) are
currently insulin-free, in some cases for up to one year. In the
course of the study, two patients voluntarily withdrew due to side
effects of the anti-rejection therapy and six graft failures were
reported following initial transplant. When these patients are
included in the analysis, the rate of insulin independence is 52% at
this point in the trial. The remaining patients, at various stages in
their treatment are currently exhibiting decreased insulin
requirements. Differences in success rates between individual
clinical centers were noted, which investigators say underscore the
challenges that lie ahead in the widespread adoption of the
technique.
Presenting their preliminary findings at the 2003 American Transplant
Congress held in Washington, DC, the investigators discussed the
results from the approximate midway point of the study that aims to
validate the success reported by the Edmonton transplant team in June
2000. With nine clinical centers participating in the trial, the ITN
study is the largest-scale clinical investigation of islet
transplantation to date. The ITN and the trial are supported by the
National Institute of Allergy and Infectious Diseases, with
additional funding from the National Institute of Diabetes and
Digestive and Kidney Diseases and the Juvenile Diabetes Research
Foundation.
Dr. James Shapiro, leader of the University of Alberta team that
developed the protocol and principal investigator of the ITN trial is
optimistic, although cautious, about the early results.
"Clearly, the ITN has confirmed that islet transplantation can be of
great benefit to patients with serious and unstable type 1 diabetes.
And importantly we have found that, with care, the technique can
indeed be applied successfully at multiple clinical facilities."
While 12 patients are currently insulin-free, 16 others at various
stages in their treatment continue to exhibit good islet function, as
measured by decreased insulin requirements and fewer hypoglycemic
events. Further transplants are required in some patients and
continued monitoring of patient and islet health are now planned
prior to the close of the trial. A complete analysis of the results
will then take place.
There was no clear explanation for graft failure in six of the
patients enrolled in the trial. In some cases, physicians were unable
to achieve adequate levels of immunosuppression to prevent rejection
and in others, the islets produced insufficient insulin following
transplantation.
According to investigators, differences in success rates were noted
between clinical centers. Significantly better results were obtained
at the three most experienced clinical centers, which together
reported over 90% of patients achieving insulin-free status, and
requiring fewer transplants to do so. The investigators believe that
this "experience factor" is particularly important in the islet
preparation procedures. "One of the keys to a successful islet
transplant is producing high quality islets," said Dr. Camillo
Ricordi, one of two co-principal investigators of the trial and
Scientific Director of the Diabetes Research Institute at the
University of Miami. "Islet preparation procedures are very complex
and require a large investment of time and effort to do well. It is
as much an art as it is a science."
The islet isolation procedure is a critical first-step in the
protocol, in which insulin-producing cells are physically separated
from the surrounding tissue of donor pancreas. Damage to the islets
during this process is not uncommon even at the most experienced
centers, and can result in impaired insulin production once
transplanted. The investigators are confident that as centers gain a
greater expertise with the islet preparation procedures, rates of
insulin independence will improve.
Dr. Robert Goldstein, Chief Scientific Officer of the Juvenile
Diabetes Research Foundation International (JDRF) believes this
underscores fundamental challenges that continue to impede islet
transplantation’s emergence into mainstream medicine: the shortage of
donor pancreases.
"Even with a perfect islet preparation method, we will still be faced
with a critical shortage of donor pancreases," said Goldstein. "So,
as we’ve known all along, a new, alternative source is needed that
provides islets in sufficient quantity and with consistent quality."
In the past several years, both the National Institutes of Health and
the JDRF have invested heavily in the development of alternative
islet sources, including adult stem cells and others.
An additional concern facing the islet transplant community is the
potential toxicity of the life-long immunosuppressive therapy
required to prevent rejection of the transplanted islets.
The anti-rejection drugs used in the ITN trial have, to date, been
relatively well tolerated with few serious adverse events and only
minor complications noted. While two patients voluntarily withdrew
from the trial due to side effects of the drugs, they have suffered
no ill effects of the procedure and remain on insulin therapy. Even
so, there are potential serious long-term risks associated with
immunosuppression that currently limit islet transplants to only the
most unstable diabetes patients, and make the procedure unsuitable
for children.
*****!!!!!The ITN will begin two additional single-center trials in
the coming months that will test new, short-term immune tolerance
therapies that are believed to provide a safer and more
immunologically targeted means of preventing transplant rejection.
"In some ways, the research community is already thinking beyond
Edmonton," said Dr. Bernhard Hering, co-principal investigator of the
trial and Director of the Islet Transplant Program at the University
of Minnesota. "Edmonton remains a remarkable success and an important
benchmark for the future, but at the same time, we are beginning to
move forward in addressing the remaining issues. The multicenter
trial is helping define these issues."
Dr. Shapiro, credited with defining the Edmonton Protocol, agrees
that the initial results from the ITN trial ultimately provide a
solid basis for advancing islet transplantation forward.
"We’re getting there. The multicenter trial is doing what we intended
it to do – to confirm that it can free patients from insulin, to
prove that it can work in different places and to define and address
the issues involved in making this viable treatment option for a
greater number of diabetes patients," said Shapiro.
The nine clinical sites participating in the trial are: University of
Alberta (Canada); University of Miami; University of Minnesota;
Harvard Medical School; Pacific Northwest Research Institute;
Washington University St. Louis; Justis-Liebig University (Germany);
University of Milan (Italy); and University Hospital of Geneva
(Switzerland).
The ITN investigators expect to complete the remaining transplants in
the multicenter trial by year’s end, with two additional years of
follow-up to assess the safety and efficacy of the technique.
The Immune Tolerance Network is an international research consortium
that aims to accelerate the clinical development of immune tolerance
therapies for use in transplantation, autoimmune diseases and allergy
and asthma. Headquartered at the University of California San
Francisco, the ITN is comprised of over 80 leading physicians and
scientists from over 40 institutions in 9 countries world-wide. The
ITN is sponsored by the National Institute of Allergy and Infectious
Diseases, with additional funds provided by the National Institute of
Diabetes and Digestive and Kidney Diseases and the Juvenile Diabetes
Research Foundation. Additional information on the Immune Tolerance
Network may be found at ***** www.immunetolerance.org. *****!!!
The ITN multicenter clinical trial of the Edmonton Protocol for islet
transplantation is closed for patient recruitment.