Clinical trial NCT00315588: Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation
Official title: Islet Cell Transplantation in Patients With Type I Diabetes With Previous Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: Islet Transplantation
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Health Resources and Services Administration (HRSA)
name: Diabetes Research Institute Foundation
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2006-04-18
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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

Eligibility criteria: 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.

Primary outcomes:
measure: Insulin Independence.
timeFrame: 1 year
Secondary outcomes:
measure: Stimulated C-peptide Greater Than 0.5 ng/ml
timeFrame: 1 year
measure: Reduction of Insulin Requirements
timeFrame: 1year
measure: Reduction in Severe Hypoglycemia, Improvement in Hypoglycemia Awareness
timeFrame: 1 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: Diabetes Research Institute
state: Florida
Study officials:
affiliation: University of Miami
name: Rodolfo Alejandro, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cure P, Pileggi A, Froud T, Messinger S, Faradji RN, Baidal DA, Cardani R, Curry A, Poggioli R, Pugliese A, Betancourt A, Esquenazi V, Ciancio G, Selvaggi G, Burke GW 3rd, Ricordi C, Alejandro R. Improved metabolic control and quality of life in seven patients with type 1 diabetes following islet after kidney transplantation. Transplantation. 2008 Mar 27;85(6):801-12. doi: 10.1097/TP.0b013e318166a27b.
citation: Faradji RN, Froud T, Messinger S, Monroy K, Pileggi A, Mineo D, Tharavanij T, Mendez AJ, Ricordi C, Alejandro R. Long-term metabolic and hormonal effects of exenatide on islet transplant recipients with allograft dysfunction. Cell Transplant. 2009;18(10):1247-59. doi: 10.3727/096368909X474456.
citation: Tharavanij T, Betancourt A, Messinger S, Cure P, Leitao CB, Baidal DA, Froud T, Ricordi C, Alejandro R. Improved long-term health-related quality of life after islet transplantation. Transplantation. 2008 Nov 15;86(9):1161-7. doi: 10.1097/TP.0b013e31818a7f45.