Overview

This trial has been completed.

Condition diabetes mellitus, type 1
Treatment islet transplantation
Phase phase 2
Sponsor Rodolfo Alejandro
Collaborator National Institutes of Health (NIH)
Start date December 2000
End date May 2014
Trial size 7 participants
Trial identifier NCT00315588, 2000/0329

Summary

The purpose of this study is to reverse hyperglycemia and insulin dependency, by islet cell transplantation, in patients with type 1 diabetes mellitus who have a stable kidney allograft.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
islet transplantation
Islet transplantation

Primary Outcomes

Measure
The endpoint of this clinical trial will be the functional capability of the islet allograft to normalize glucose metabolism in the absence of insulin therapy.
time frame: 3 years

Secondary Outcomes

Measure
Partial graft function, as evidenced by basal C-peptide greater than 0.5 ng/ml
time frame: 3 years
Reduction in insulin requirements in those patients who do not achieve insulin independence
time frame: 3 years
Elimination or reduction in the incidence of hypoglycemic coma or unawareness
time frame: 3 years

Eligibility Criteria

Male or female participants from 18 years up to 60 years old.

Inclusion Criteria: 1. Patients between 18 and 60 years of age. 2. Patients with type 1 diabetes mellitus. 3. Patients with a renal transplant that is more than 6 months old. 4. Patients with stable renal graft function for the preceding 6 months, i.e. no episodes of rejection and changes in serum creatinine no more than 0.5 mg/dl from baseline. 5. Patients who are taking tacrolimus, sirolimus +/- steroids for maintenance immunosuppression for at least 6 months and are tolerating levels satisfactory for islet transplantation without severe complications. 6. Patients with a body mass index (BMI) of less than or equal to 26. Exclusion Criteria: 1. Stimulated or basal C-peptide > 0.3 ng/ml. 2. Patients with unstable renal function - serum creatinine greater than 0.5 mg/dl above baseline. 3. Patients with proteinuria (albuminuria > 300 mg in 24 hours +/- protein) of new onset since kidney transplantation. If proteinuria or albuminuria is thought to originate from the native kidney(s) this will not be an exclusion criterion. 4. Patients with corrected creatinine clearance of less than 40. 5. Patients weighing more than 80 kg. 6. Patients with a body mass index (BMI) of greater than 26. 7. Insulin requirement > 1.0 U/kg/d. 8. Anemia (hemoglobin: males < 11.0 g/dl; females < 10.0 g/dl). 9. Abnormal liver function tests (consistently > 1.5 x normal range). 10. Unstable diabetic retinopathy. 11. Evidence of acute or chronic active Epstein-Barr virus (EBV) infection (IgM ≥ IgG). Patients will be eligible if serological testing becomes consistent with previous exposure (i.e. IgG > IgM). 12. Patients with history of malignancy or current malignancy other than non-melanomatous skin cancer, or finding of any lesions or symptoms during screening that are suspicious for malignancy, until properly investigated and ruled out. 13. Patients with elevation of prostate-specific antigen > 4 unless malignancy has been excluded. 14. Patients with unstable cardiovascular status. 15. Patients with active infections until adequately treated, unless treatment is not judged as necessary by the investigators (including, but not limited to, mild skin and nail fungal infections). 16. Patients with serological evidence of infection with HIV, human t cell lymphotropic virus 1 (HTLV 1), HTLV 2, or hepatitis B (patients with serology consistent with previous vaccination and a history of vaccination are acceptable). 17. Patients with history and/or serological evidence of hepatitis C (those patients with hepatitis C, already transplanted in this protocol will continue in this trial). 18. Positive tuberculin test (unless proof of adequate treatment for latent tuberculosis can be provided). 19. Patients with active peptic ulcer disease, gallstones, hepatic hemangioma, or portal hypertension. 20. Patients who are pregnant or breastfeeding, or who intend to procreate. 21. Patients who are sexually active females who are not: - post-menopausal, - surgically sterile, or - using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices combined with spermicidal gel are acceptable; condoms used alone are not acceptable). 22. Active alcohol or substance abuse; smoking in the last 6 months. 23. Patients with evidence of sensitization, i.e. panel reactive antibody (PRA) testing greater than 20%. 24. Lack of updated immunizations per current Centers for Disease Control (CDC) guidelines, as well as immunization against hepatitis B, pneumococcus, and influenza (during season), unless medically contraindicated. 25. Patients with psychogenic factors, which are judged at psychological evaluation, which make it unsafe to undergo islet transplantation, or which preclude therapeutic compliance. 26. Patients with any condition or any circumstance that would make it unsafe to undergo an islet transplant.

Additional Information

Official title Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation
Principal investigator Rodolfo Alejandro, M.D.
Description 1. To reverse hyperglycemia and insulin dependency by islet cell transplantation, in patients with Type 1 Diabetes Mellitus who have a stable kidney allograft; 2. To eliminate the incidence of hypoglycemic coma and unawareness by islet cell transplantation; 3. To assess long-term function of successful islet cell transplants; 4. To determine whether the natural history of the microvascular, macrovascular and neuropathic complications of Diabetes Mellitus are altered following successful transplantation of islet cells. 5. To assess the effect of exenatide to improve islet graft function and survival in subjects that demonstrate partial graft loss and have returned to using exogenous insulin. 6. To assess the ability of exenatide to improve islet survival at time of islet transplantation
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by University of Miami.