Gender
All
Age Group
18 Years to 65 Years
Accepting Healthy Volunteers
No
Inclusion Criteria:
1. Male and female patients 18 to 65 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. Clinical history compatible with Type 1 Diabetes Mellitus (T1DM) with onset of disease
at <40 years of age, insulin-dependence for ≥5 years at the time of consent, and a sum
of patient age and insulin dependent diabetes duration of ≥28.
5. Absent stimulated c-peptide (<0.3 ng/mL) in response to a mixed meal tolerance test
(MMTT; measured during the 4 hour test).
6. Involvement in intensive diabetes management defined as self-monitoring of glucose
values no less than a mean of three times each day averaged over each week and by the
administration of three or more insulin injections each day or insulin pump therapy.
Such management must be under the direction of an endocrinologist, diabetologist, or
diabetes specialist with at least 3 clinical evaluations during the 12 months prior to
study consent.
7. At least one episode of severe hypoglycemia in the 12 months prior to study consent.
8. Reduced awareness of hypoglycemia. More information about this criterion, including
specific definitions of hypoglycemia unawareness, is in the protocol.
Exclusion Criteria:
1. Body mass index (BMI) >30 kg/m2
2. Insulin requirement >1.0 IU/kg/day
3. Glycated Haemoglobin (HbAlc) >13%.
4. Untreated proliferative diabetic retinopathy.
5. Blood Pressure: Systolic blood pressure (SBP) >160 mmHg or Diastolic Blood Pressure
(DBP) >100 mmHg.
6. Measured glomerular filtration rate <70 mL/min/1.73m2 (More information about this
criterion is in the protocol
7. Presence or history of macroalbuminuria (>300 mg/g creatinine).
8. Presence or history of panel-reactive anti-HLA antibodies >30%
9. For female subjects of child bearing potential: Positive pregnancy test, presently
breast-feeding, or unwillingness to use effective contraceptive measures for the
duration of the study and 4 months after discontinuation. For male subjects: intent to
procreate during the duration of the study or within 4 months after discontinuation or
unwillingness to use effective measures of contraception. More information about this
criterion is in the protocol.
10. Presence or history of active infection including hepatitis B, hepatitis C, HIV, or
tuberculosis (TB). Subjects with laboratory evidence of active infection are excluded
even in the absence of clinical evidence of active infection.
11. Patients with negative screen for Epstein Barr Virus by Immunoglobulin G (IgG)
determination. More information about this criterion is in the protocol,
12. Invasive aspergillus, histoplasmosis, or coccidioidomycosis infection within one year
prior to study consent.
13. Any history of malignancy except for completely resected squamous or basal cell
carcinoma of the skin.
14. Known active alcohol or substance abuse.
15. Baseline Hb below the lower limits of normal at the local laboratory for patients
initially being enrolled into study.
16. Severe co-existing cardiac disease, characterized by any one of these conditions:
- Recent myocardial infarction (within past 6 months).
- Left ventricular ejection fraction <30%.
- Uncontrolled coronary artery disease.
- Known hypercoagulative state or
- International Normalized Ratio > 1.8
17. Uncontrolled hyperlipidemia (fasting LDL cholesterol >130mg/dL and/or fasting
triglycerides >200mg/dL).
18. Persistent elevation of liver function tests. More information on this criterion is in
the protocol
19. Severe unremitting diarrhea, vomiting or other gastrointestinal disorders potentially
interfering with the ability to absorb oral medications (for example untreated celiac
disease).
20. Untreated Graves' disease
21. Portal hypertension
22. Receiving treatment for a medical condition requiring chronic use of systemic
steroids, except for the use of ≤ 5 mg prednisone daily, or an equivalent dose of
hydrocortisone, for physiological replacement only.
23. Treatment with any anti-diabetic medication other than insulin within 4 weeks of
transplant, More information on this criterion is in the protocol
24. Use of any investigational agents within 4 weeks of consent
25. Administration of live attenuated vaccine(s) within 2 months of consent.
26. Any medical condition that, in the opinion of the study investigator, will interfere
with safe participation in the trial.
27. Treatment with any immunosuppressive regimen at the time of consent.
28. A previous islet transplant.
29. A previous pancreas transplant. More information on this criterion is in the protocol
30. Known allergy or hypersensitivity to polymers More information on this criterion is in
the protocol
31. Islets from non-heart beating donors will be excluded as well as from CDC high-risk
donors.
32. Presence of colostomy/ileostomy, incisional hernia or other deformity of the abdominal
wall precluding implantation of the Cell Pouch.
33. History of malignant hypertension or other conditions precluding general anesthesia.
34. Use of coumadin or other anticoagulant therapy (except aspirin) or subject with
prothrombin time (PT-INR) > 1.5.
