Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Islet Cell Transplantation Alone in Patients With Type 1 Diabetes Mellitus: Steroid-Free Immunosuppression

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by University of Miami.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Health Resources and Services Administration (HRSA)
Information provided by (Responsible Party):
Rodolfo Alejandro, University of Miami
ClinicalTrials.gov Identifier:
NCT00306098
First received: March 17, 2006
Last updated: November 26, 2013
Last verified: June 2012
  Purpose

SPECIFIC AIMS:

  1. To reverse hyperglycemia and insulin dependency in patients with Type 1 Diabetes Mellitus by islet cell transplantation;
  2. To eliminate the incidence of hypoglycemia coma and unawareness in patients with Type 1 Diabetes Mellitus by islet cell transplantation;
  3. To assess long-term safety and function of successful islet cell transplants in patients with Type 1 Diabetes Mellitus;
  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; and
  5. To assess the effect of infliximab in preventing early islet destruction, and thereby eliminating the need for a second donor's islet cells.
  6. To assess the effect of etanercept in preventing early islet destruction.
  7. To assess the effect of exenatide to improve islet graft function and survival in subjects that have returned to using exogenous insulin.
  8. To assess the ability of exenatide to improve islet survival at time of transplantation.

Condition Intervention Phase
Diabetes Mellitus, Type I
Drug: islets
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Islet Cell Transplantation Alone in Patients With Type 1 Diabetes Mellitus: Steroid-Free Immunosuppression

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • a1c less than 6.5 without severe hypoglycemia [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Secondary end-points will include: partial graft function, as evidenced by baseline C-peptide greater than 0.5 ng/ml [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • evidence for reduction in insulin requirements in those patients who do not achieve insulin independence [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • improvement in metabolic control as evidenced by improvement in: HbA1C (should be < 7), mean amplitude of glycemic excursions (MAGE), mean glucose meter readings, continuous glucose monitoring, OGTT, and acute C-peptide response to arginine challenge [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • elimination or reduction in the incidence of hypoglycemic coma or unawareness [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • improvement in or decreased progression of microvascular, macrovascular and neuropathic complications of diabetes [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • assessment of efficacy of infliximab in preventing early rejection - number of subjects achieving insulin independence with a single infusion [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • assessment of efficacy of etanercept in preventing early rejection - number of subjects achieving insulin independence with a single infusion [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • assessment of EXN to re-establish insulin independence or increase insulin secretion - reduction in insulin requirements with restoration of satisfactory glycemic control [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • assessment of EXN to improve islet survival at time of islet transplantation - number of subjects achieving insulin independence with a single infusion [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: December 2000
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Islet transplantation Drug: islets
Islet transplantation

Detailed Description:

This Phase II trial will have 3 groups: Group A will receive islets from 2 donors and will not receive infliximab. Group B will receive, in addition to Daclizumab, Sirolimus, and Tacrolimus, a dose of infliximab and islets from a single donor, as per the Edmonton protocol. Everything else about the clinical trial will be the same for both groups. The first 4 patients will be assigned to Group A, the next 4 patients to Group B, the next 4 patients to Group A, and the next 4 patients to Group B (total =16). Patients in Group A will receive 1-2 transplants with cells from 2 donors. If the second donor pancreas is received and satisfactory at the same time as the first pancreas, one islet infusion will be used to infuse cells from both donors. If the second pancreas is not received until after the first transplantation, a second islet infusion will be done. A second course of five doses of Daclizumab will be started on the day of the second islet infusion).

In order to determine if prolonged administration of etanercept, in combination with transplantation of cultured islets, will prevent TNF-α production and enhance engraftment, we have added Group C to the current protocol. Group C, in addition to Daclizumab, Sirolimus, and Tacrolimus, will receive Etanercept in the peri-transplant period and islets from one or more donors. The last 24 patients included in this Protocol will be in Group C if they are new, or in Group A and B Supplemental Infusion if they had previous transplants. Any Group A or B participants who are eligible for a supplemental infusion will receive etanercept but no infliximab.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients between 18 and 65 years of age
  2. Patients with type 1 diabetes mellitus for more than 5 years duration
  3. One or more of the following:

    • Hypoglycemia unawareness - judged by history of blood sugars <54 on glucometer without symptoms and/or hypoglycemic episodes requiring assistance from either family, glucagon administration or emergency services
    • Poor diabetes control (HbA1c>8% or >2 visits/yr to hospital for treatment of ketoacidosis) despite intensive insulin therapy
    • Progressive complications of type 1 diabetes mellitus
  4. Body Mass Index (BMI) ≤26

Exclusion Criteria:

  1. c-peptide > 0.3ng/ml basal or stimulated;
  2. untreated proliferative diabetic retinopathy;
  3. HbA1C >12%;
  4. creatinine clearance <60;
  5. serum creatinine consistently >1.6 mg/dl;
  6. macroalbuminuria >300mg albumin in 24 hours;
  7. presence of panel reactive antibodies (PRA) >20%;
  8. previous/concurrent organ transplantation (except previous unsuccessful islet cell transplant;
  9. malignancy or previous malignancy (except non-melanomatous skin cancer);
  10. x-ray evidence of pulmonary infection;
  11. active infections;
  12. active peptic ulcer disease, gall stones, hemangioma, or portal hypertension
  13. serological evidence of HIV, HbsAg or HCV; serological evidence of active EBV (IgM>IgG) or EBV negative serology;
  14. PPD conversion or positive PPD without historic completion of appropriate prophylactic treatment;
  15. abnormal liver function test;
  16. anemia (hemoglobin <12.0);
  17. hyperlipidemia (fasting serum triglycerides >200mg/dl and/or fasting serum cholesterol >240 mg/dl and/or fasting LDL cholesterol >140 mg/dl);
  18. BMI above 26;
  19. unstable cardiovascular status; prostate specific antigen (PSA) >4;
  20. pregnancy or breastfeeding;
  21. sexually-active females who are not: a) post-menopausal, b) surgically sterile, or c) not using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices are acceptable; condoms used alone are not acceptable);
  22. alcohol abuse, substance abuse or smoking within the previous 6 months; insulin requirement >1u/kg/day and any condition or any circumstance that makes it unsafe to undergo an islet cell transplant.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00306098

Locations
United States, Florida
University of Miami, Diabetes Research Institute
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
Health Resources and Services Administration (HRSA)
Investigators
Principal Investigator: Rodolfo Alejandro, M.D. University of Miami, Diabetes Research Institute
Principal Investigator: Camillo Ricordi, M.D. University of Miami, Diabetes Research Institute
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Rodolfo Alejandro, Professor of Medicine, University of Miami
ClinicalTrials.gov Identifier: NCT00306098     History of Changes
Other Study ID Numbers: 2000/0196, NIH #1U42 RR016603-01, HRSA # 1 R38OT01367-01-00
Study First Received: March 17, 2006
Last Updated: November 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
Transplantation, Islets of Langerhans

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on November 20, 2014