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[IP] interesting clinical trial...

hi all,
it's been a long time since i've visited, and i'm enjoying catching up. i
don't think any of you remember me, but i'm the over eager one who went on
the pump one month after being diagnosed-thanks to many of you! i've been
pumping for 9 months
now....um, maybe i'll get the hang of this someday..sigh.. but that's
another letter...
ran across this trial and since "compliance" was part of the criteria, i
figure anyone on this list is good! since i've only had this for 10 months
i don't qualify, but thought some of you might benefit.

leann marcucci
email @ redacted

from http://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_01-DK-0036.html

Protocol Number: 01-DK-0036 


Title: Solitary Islet Transplantation for Type 1 Diabetes Mellitus Using
Steroid Sparing Immunosuppression 
Number: 01-DK-0036 
Summary: This study will test whether a new islet transplant procedure
will enable patients with type 1 diabetes mellitus to stop insulin
therapy. Islets are cell clusters in the pancreas that contain
insulin-producing cells. The new procedure features three important
advances, first developed by a group in Edmonton, Canada, over the way
islet transplants have traditionally been performed: 1) the islets are
transplanted immediately after they are removed from the donor; 2) islets
are transplanted from two different donors in order to obtain the number
of islets in a normal pancreas; and 3) the anti-rejection drug regimen is
designed to reduce the harmful side effects of "conditioning"
chemotherapy. (In the standard transplant procedure, patients receive
intensive chemotherapy following the transplant. This study will use no
radiation and lower-dose chemotherapy.)

Patients between the ages of 18 and 65 with the diagnosis of type 1
diabetes mellitus for at least 5 years may be eligible for this study.
Candidates will be screened with a medical history and physical
examination, blood tests, chest X-ray and tuberculin skin test,
electrocardiogram and exercise test for heart function, abdominal
ultrasound, psychological evaluation, and an arginine stimulated c-peptide
test. The latter test determines if the patient is producing any insulin.
Eligibility is restricted to patients who make no insulin at all. 

The study has an active phase lasting 15 months and follow-up that
continues indefinitely. Patients will receive 10,000 "islet equivalents"
per kilogram (2.2 pounds) of body weight. This will likely require two
separate transplant procedures from two donors. Before the first surgery,
patients will be given anti-rejection (immune suppressing) drugs,
including FK506 and rapamycin (orally) and daclizumab (intravenously). The
islets will be infused through a tube placed in the portal vein (the large
vein that feeds the liver). After surgery, patients will receive insulin
intravenously for 24 hours. They will then have an abdominal ultrasound
and blood tests to determine liver function. If fewer than 10,000 islets
were transplanted, patients will continue insulin treatment, with the
dosages adjusted to account for the transplanted islets. They will take
Daclizumab every 2 weeks, and FK506 and rapamycin daily. Blood tests to
follow how much of these drugs are in the blood stream will be performed
daily at first and then weekly after blood levels of these drugs
stabilize. They will be given antibiotics to prevent infections. The
arginine test will be repeated 2 weeks after the transplant and
periodically thereafter. Blood will be drawn weekly to check drug levels,
and monthly for other tests. The investigators will track daily insulin
requirements, and these will be recorded monthly.

Patients who require a second transplant to achieve the required amount of
islets will return for the procedure when a compatible organ is donated.
The second procedure will be done as described above. As before, insulin
will be infused for 24 hours following surgery. It will then be stopped,
however, and will not be resumed unless blood glucose levels reach above
180 milligrams/deciliter. Patients will continue taking FK506 and
rapamycin indefinitely. Daclizumab will be given every 2 weeks for 4 doses
following the second transplant, and then stopped. Patients will take an
antiviral called gancyclovir for 14 weeks and another antibiotic for 1
year following surgery. For the first year after surgery, patients will
have frequent blood tests to monitor drug levels and immune function. They
will return to NIH for a complete history and physical examination 2 and 3
years after the final islet transplant and will be contacted yearly by
phone to ascertain their general health status and whether they remain
insulin independent.

Sponsoring Institute: 
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
Recruitment Detail 
Type: Active Accrual Of New Subjects 
Gender: Male & Female 
Referral Letter Required: No 
Population Exclusion(s): None

Eligibility Criteria: 
Patients with T1DM for at least 5 years will be eligible for the study
provided they exhibit one of the following: 1) hypoglycemic unawareness,
as defined by inability to sense hypoglycemia until the blood glucose
falls to less than 54 mg/dl or greater than one hypoglycemic reaction in
the preceding 20 months and that required outside help and was not
explained by a clear precipitant; 2) metabolic instability, as defined by:
a) recurrent hypoglycemic or ketoacidotic events requiring more than two
hospitalization within the preceding 12 months, b) disruption in quality
of life or direct potential danger to the patient or others around them,
with more than two hospital admissions or more than four weeks off school
or work, or where the individual is no longer able to provide essential
care for others; 3) evidence of early but progressive secondary diabetic
complications but which have not progressed to end-stage renal failure; 4)
failure of intensive insulin management, as judged by an endocrinologist
independent of study investigators.

Patients must not have significant cardiac disease as defined by: a) a
history of a myocardial infarction with the past 6 months, b) coronary
angiographic evidence of non-correctable arteriopathy, c) evidence of
ischemia on a functional cardiac examination.

Patients must not have active alcoholism or other substance abuse
(including cigarette smoking) within the past 6 months.

Patients must not fail to clear a psychological or psychiatric screen (as
assessed by psychological or psychiatric consultation).

Patients must not have a history of non-adherence. If adherence has been
questionable, then an adherence agreement must be entered and compliance
demonstrated for at least 3 months.

Patients must not have active infection including hepatitis B or C, HIV
positivity, a positive Mantoux test (unless previously immunized with
BCG), or any X-ray evidence of pulmonary infection.

Patients must not have a history of malignancy except squamous and basal
cell skin cancer, unless disease free for at least 5 years, and cleared by
an independent oncological consultation.

Patients must not have obesity (defined by a body mass index of greater
than 28).

Patients must not have C-peptide values greater than or equal to 0.3 pm/ml
following a 5.0 gram intravenous arginine infusion.

Patients must have the ability to provide informed consent.

Patients must not be aged less then 18 or more than 65 years.

Patients must not have a creatine clearance of less than 60 ml/min/m2, or
macroalbuminuria of greater than 300 mg/24h.

Patients must not have a baseline Hb of less than 12 g/dl in women, or
less than 13 g/dl in men.

Patients must not have a WBC count of less than 3,000/mm(3).

Patients must not have a platelet count of less than 100,000/mm(3).

Patients must not have baseline LFTs outside of normal range.

Patients must not have the presence of gallstones, liver hemangioma, or
evidence of portal hypertension on baseline U/S.

Patients must not have untreated proliferative retinopathy.

Female patients must not : have a positive pregnancy test, intent for
future pregnancy, or any subject of reproductive age unable or unwilling
to use an acceptable method of contraception.

Female subjects must not be breastfeeding.

Patients must not have had a previous transplant, or evidence of known
previous or current anti-HLA antibody.

Patients must not have an insulin requirement of greater than 0.7

Patients must not have an HbA1C of greater than 12 percent.

Patients must be able to reach the hospital for transplantation within 6
hours of notification.

Patients must not have untreated hyperlipidemia.

Special Instructions: Currently Not Provided 
Islet Isolation 
Recruitment Keywords: 
Insulin Dependent Diabetes Mellitus 
Investigational Drug(s): 
Investigational Device(s): 

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:email @ redacted

Ballinger. 1972. Transplantaion of intact pancreatic islets in rats,
Surgery, Vol. 72, p. 175 

Kemp. 1973. Transplantation of isolated pancreatic islets into the portal
vein of diabetic rats, Nature, Vol. 244, p. 447 

Anonymous. 1993. The effect of intensive treatment of diabetes on the
development and progression of long-term complications in
insulin-dependent diabetes mellitus, N Engl J Med, Vol. 329, p. 977 
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