Islet Allotransplantation in Type 1 Diabetes

IRB 2006H0200

Islet transplantation can provide physiologic insulin replacement to patients with type 1 diabetes without the complications associated with whole pancreas transplantation. The purpose of this study is to achieve insulin-independence in patients with type 1 diabetes, thereby eliminating the need for exogenous insulin injections to maintain normal glucose levels, ameliorating severe hypoglycemia and potentially decreasing the development of diabetes-related complications. This study will investigate islet transplantation in subjects who have preserved renal function and subjects who have undergone cadaveric renal transplantation, since the latter subjects are already on immunosuppression. This is a single center, prospective trial of islet transplantation in subjects receiving islets alone or islets after kidney transplant. This is a phase I study investigating the use of islet transplantation for the treatment of type 1 diabetes. Subjects will be eligible for an islet transplant if they meet all of the inclusion criteria and none of the exclusion criteria outlined in the protocol. In brief, the aims of this study are to establish an islet transplant program at the Ohio State University, determine the safety of islet transplantation in islet alone and kidney transplant recipients, determine whether islet transplantation will reduce the frequency of severe hypoglycemic events, determine whether a novel steroid-free immunosuppressive protocol will prevent rejection in islet transplants and to achieve insulin independence at one year after the final islet transplant.

2006-11-01

2033-10-01

2033-10-01

Early phase I

20

Inclusion Criteria: 1. Type 1 diabetes \> 5 years 2. First islet transplant 3. Demonstrate intensive efforts to manage diabetes for last 6 months (≥4 SMBG/day, ≥3 injections of insulin/day or use of pump and ≥3 contacts with diabetes care team in last 12 months) 4. Metabolic complications: at least one of the following: •Reduced hypoglycemia awareness (inability to sense hypoglycemia until blood glucose falls to \< 54 mg/dl or \> one hypoglycemic episode in last 12 months requiring outside help and not explained by clear precipitant) •≥2 severe hypoglycemic events or ≥2 hospitalizations for diabetic ketoacidosis (DKA) in last year. 5. Ability to provide written informed consent 6. Age 18-65 7. Specific for group 2: All of above (1-6) with renal transplant at least 6 months previous Exclusion Criteria: 1. Age \< 18 years or \> 65 years 2. Inability to provide informed consent 3. Body Mass Index \> 29 kg/m2 4. Insulin requirement of \> 50 units/day 5. Stimulated C-peptide ≥ 0.2 ng/ml 6. Current panel reactive anti-HLA antibodies \>20% 7. Cardiovascular instability 8. Previous islet transplant 9. History of malignancy except squamous and basal cell skin cancer unless disease-free for \> 2 years determined by independent oncologist 10. Active peptic ulcer disease 11. Condition that may interfere with absorption of medications 12. Hemoglobin A1C \> 12% 13. Invasive aspergillus infection within one year 14. Varicella titer index \<1.0 15. Rubella titer \<10 IU/ml 16. Psychiatric disorder 17. Untreated hyperlipidemia: fasting total cholesterol \>240 mg/dl, low density lipoprotein\>130 mg/dl, or triglycerides \>200 mg/dl 18. Hemoglobin \<10 g/dl for females, and \<11 g/dl for males, white blood cell count \< 3,000/µL, platelet count of \<150,000/microliter, CD4+ count \<500/microliter 19. Liver function test abnormalities (if any value \> 1.5 times normal, candidate will be excluded. If 1-1.5 times normal, test will be repeated. If re-test value remains above normal, candidate will be excluded). 20. Prostate specific antigen \>4.0 ng/ml 21. Presence of gallstones, liver hemangioma, cirrhosis or evidence of portal hypertension 22. Untreated proliferative diabetic retinopathy 23. Females: positive pregnancy test, intent for future pregnancy, or any subject of reproductive age who is not surgically sterile and is unable or unwilling to use acceptable method of contraception 24. Female subjects who are breast-feeding 25. Adrenal insufficiency: 8am cortisol \>19 mcg/dl adequate. Values 19 mcg/dl will be followed by Adreno-Corticotropic Hormone stimulation test 26. Any disease or condition that requires use of chronic steroids 27. Coagulopathy or use of chronic anticoagulation 28. Hyperthyroidism unless treated with radioactive iodine or surgery 29. Thyroid function tests outside normal range 30. Active alcoholism or other substance abuse within the past six months 31. History of non-adherence. Questionable adherence requires agreement entered and compliance demonstrated for at least 3 months 32. Active infection including hepatitis B or C, human immunodeficiency virus positive, positive Mantoux test \[unless previously immunized with Bacillus Calmette-Guerin\], or X-ray evidence of pulmonary infection 33. Inability to reach hospital within 6 hours of notification 34. Failure to clear psychological or psychiatric screen 35. Medical condition or circumstance that investigator finds will interfere with safe completion of the study Exclusion criteria specific for group 1: 1. Receipt of previous transplant (excluding pancreas) 2. Creatinine clearance \<50 ml/minute for females and \<60 ml/minute for males or macroalbuminuria (\>500 mg/24h) Exclusion criteria specific for group 2: 1. Creatinine clearance \<40ml/minute 2. Renal transplant in last 6 months 3. Current use of corticosteroids

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 20, 'type': 'ESTIMATED'}}

2023-05-30