The purpose of this study is to evaluate the safety and efficacy of islet transplantsfrom human cadaver donors into type 1 or surgical diabetes mellitus patients whoexperience frequent acute or advanced chronic complications but do not qualify for otherislet transplant trials. Under this protocol, patients may receive intraportal alloislettransplant under one of the following scenarios: 1. islet transplant alone 2. simultaneous islet-kidney transplant, or 3)islet after kidney transplant.
The overall objective of this study is to evaluate the efficacy of islet allotransplants
for labile diabetes mellitus in patients who do not meet standard inclusion/exclusion
criteria for any other islet transplant trials in the US and are not good candidates for
a pancreas transplant. We expect that this will include patients who have surgical
diabetes (total pancreatectomy) rather than type 1 diabetes, patients who are highly
sensitized (PRA>20%), and patients who have had prior failed pancreas transplantation.
These patients may have equally severe hypoglycemia, glucose lability, and/or severe
microvascular complications, but are excluded from standard islet transplant trials
currently available in the U.S.
Biological: Allogeneic islets of Langerhans
Up to 3 intraportal infusions of cadaveric pancreatic islets of Langerhans. Each infusion
to contain at least 5,000 islet equivalents/kg body weight.
Other Name: Islets
Inclusion Criteria:
1. Male and female patients age 18 to 70 years of age.
2. Ability to provide written informed consent.
3. Mentally stable and able to comply with the procedures of the study protocol.
4. Insulin-dependent diabetes mellitus
5. Not otherwise eligible for an existing alloislet transplant protocol for type 1
diabetes mellitus
6. Involvement in intensive diabetes management, defined by at least 3 injections daily
or insulin pump therapy.
7. Meets at least one of the following criteria despite intensive efforts made in close
cooperation with their diabetic care team:
- Significant hypoglycemia unawareness or glycemic lability on conventional
insulin therapy, as evidenced by at least one of the following at screening:
- Clarke score > 4
- HYPO score >90th percentile (1047)
- Lability index (LI) >90th percentile (433 mM2/h/wk)
- A composite of a Clarke score of 4 or more and a HYPO score greater than or
equal to the 75th percentile (423) and a LI greater than of equal to the 75th
percentile (329)
- Progressive secondary complications as defined by end-stage renal disease
necessitating dialysis or renal transplantation (eligible for islet after
kidney or simultaneous islet kidney transplant) AND islet transplant appears to
provide a more satisfactory benefit to risk ratio compared to pancreas
transplantation (eg high surgical risk)
Exclusion Criteria:
1. HbA1c >10%.
2. Untreated proliferative diabetic retinopathy.
3. Uncontrolled Hypertension (SBP>160 or DBP>100)
4. For female participants: Positive pregnancy test, presently breast-feeding, or
unwillingness to use effective contraceptive measures for the duration of the study.
5. Active infection including hepatitis B, hepatitis C, HIV, or TB as determined by a
positive skin test or clinical presentation, or under treatment for suspected TB.
6. Any history of malignancy except for completely resected squamous or basal cell
carcinoma of the skin.
7. Receiving treatment for a medical condition requiring chronic use of systemic
steroids, except for use of prednisone <5 mg per day for kidney transplant
recipients or physiologic hydrocortisone replacement.
8. Persistent elevation of liver function tests at the time of study entry. Persistent
SGOT (AST), SGPT (ALT), Alk Phos or total bilirubin, with values >1.5 times normal
upper limits will exclude a patient.
9. Severe co-existing cardiac disease, characterized by any one of these conditions:
- recent myocardial infarction (within past 6 months).
- evidence of ischemia on functional cardiac exam within the last year.
- left ventricular ejection fraction <30%.
10. If diabetes is secondary to total pancreatectomy, participants will be considered
only if >1 year out from surgery, medically stable, without severe issues with bowel
function or pain management that may interfere with safe completion of the trial.
11. History of alcoholism
12. Any medical condition that, in the opinion of the investigator, will interfere with
the safe completion of the trial.
University of Minnesota
Minneapolis, Minnesota, United States
Investigator: Alisha Albrecht
Contact: 612-624-8402
albre441@umn.edu
Melena Bellin, MD
612-625-4686
bell0130@umn.edu
Bernhard J Hering, M.D., Principal Investigator
University of Minnesota