Delayed Mycophenolate Mofetil in Single-Donor Islet Allotransplantation in Type 1 Diabetes

This study has been completed.
Sponsor:
Collaborators:
Roche Pharma AG
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT00285233
First received: January 30, 2006
Last updated: July 31, 2012
Last verified: July 2012
  Purpose

The objective of this study is to assess the safety and efficacy of islet allotransplantation for the reestablishment of stable glycemic control in patients with type 1 diabetes, using anti-thymocyte globulin induction immunosuppression with sirolimus, mycophenolate mofetil and low dose tacrolimus maintenance immunosuppression.


Condition Intervention Phase
Type 1 Diabetes
Hypoglycemia
Biological: Allogeneic islets of Langerhans transplant
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Pilot Study of Delayed Mycophenolate Mofetil Instead of Tacrolimus Combined With Anti-thymocyte Globulin, Daclizumab, Etanercept, and Sirolimus in Single-donor, Solitary Islet Allograft Recipients With Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • Assess the incidence and severity of hypoglycemia in type 1 diabetic subjects receiving an islet allotransplant and immunotherapy during the first year posttransplant. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Assess liver laboratory tests during the first year following intraportal islet allotransplantation. [ Time Frame: 1 yr ] [ Designated as safety issue: Yes ]
  • Assess the incidence, type, and severity of islet transplant-related infectious complications during the first year posttransplant. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Assess the proportion of recipients who develop alloantibodies directed at donor alloantigens during the first year posttransplant. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Monitor the incidence, timing, and severity of adverse events as well as their relationship to the islet transplant procedure and additional protocol-regulated treatment products during the first year after islet transplantation. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assess the proportion of type 1 diabetic subjects receiving delayed mycophenolate mofetil instead of tacrolimus who achieve insulin independence in the first year after transplantation of allogeneic islets. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Assess the proportion of type 1 diabetic islet allograft recipients with full and partial alloislet function at one year post transplant. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Assess the glycemic control, insulin secretory responses, and the glucose disposal rate during the first year posttransplant. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Effect of donor age, pretransplant islet insulin secretory response, # of transplanted islet equivalents, # of transplanted beta cells, pretransplant insulin action, recipient BMI and immunosuppressive therapy on safety and efficacy. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Assess, in a selected group of islet allotransplant recipients, the autoimmune and alloimmune responses to transplanted islets at intervals during the first year posttransplant. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: September 2000
Study Completion Date: March 2005
Primary Completion Date: September 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Biological: Allogeneic islets of Langerhans transplant
Allogeneic islets of Langerhans transplant
Other Name: Islet transplant

Detailed Description:

To assess the safety and efficacy of a new single-donor islet allotransplant protocol focusing on minimization of ischemic damage by the two-layer pancreas preservation technique, attenuation of posttransplant nonspecific inflammatory responses by etanercept and anti-thymocyte globulin, deletion/inactivation of autoreactive T cells by anti-thymocyte globulin and daclizumab induction immunotherapy, and potent yet non-diabetogenic maintenance immunosuppression with sirolimus and delayed mycophenolate mofetil instead of tacrolimus for the reestablishment of stable glycemic control in recipients with type 1 diabetes.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Primary islet allotransplant
  2. Type 1 diabetes mellitus, complicated by at least one of the following situations that persist despite intensive efforts in close cooperation with their diabetes care team:

    1. Metabolic lability/instability;
    2. Reduced awareness of hypoglycemia;
    3. Persistently poor glucose control (as defined by HgbA1c>10% at the end of six months of intensive management efforts with the diabetes care team);
    4. Progressive secondary complications.
  3. Age 18 and older
  4. Able to give written informed consent

Exclusion Criteria:

  1. Known hypersensitivity to rabbit proteins.
  2. Presence of history of panel-reactive anti-HLA antibodies (>10%).
  3. Insufficient cardiovascular reserve.
  4. Creatinine clearance <60 mL/min/m2.
  5. Portal hypertension, abnormal liver enzyme tests, or history of significant liver disease.
  6. History of malignancy within 5 years.
  7. Active peptic ulcer disease.
  8. Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications.
  9. Pregnancy or breast-feeding.
  10. Active infections.
  11. Serological evidence of infection with HIV, or HBsAg or HCVAb positive within the previous 12 months prior to transplantation.
  12. Negative screen for Epstein-Barr Virus (EBV) by an EBNA method
  13. Evidence of infiltrate, cavitation, or consolidation on chest x-ray during pre-study screening.
  14. Schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medications.
  15. Ongoing substance abuse; drug or alcohol.
  16. Recent history of noncompliance.
  17. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00285233

Locations
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Roche Pharma AG
Juvenile Diabetes Research Foundation
Investigators
Principal Investigator: Bernhard J. Hering, M.D. University of Minnesota - Clinical and Translational Science Institute
  More Information

Additional Information:
Publications:
Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT00285233     History of Changes
Other Study ID Numbers: 0006M55241
Study First Received: January 30, 2006
Last Updated: July 31, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Mycophenolate mofetil
Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014