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Islet Cell Transplantation Alone and CD34+ Enriched Donor Bone Marrow Cell Infusion in Patients With Type 1 Diabetes Mellitus; Steroid Free Regimen
This study is currently recruiting participants.
Verified by University of Miami, June 2008
Sponsors and Collaborators: University of Miami
National Institutes of Health (NIH)
Information provided by: University of Miami
ClinicalTrials.gov Identifier: NCT00315614
  Purpose

SPECIFIC AIMS:

  1. To reverse hyperglycemia and insulin dependency in patients with Type 1 diabetes mellitus by islet cell transplantation.
  2. To induce a state of donor specific tolerance and eliminate the need for continuous immunosuppressive therapy by simultaneous transplantation of donor bone marrow cells with islets and utilization of the monoclonal antibody Campath-1H for induction of Immunosuppression.
  3. To assess long-term 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 are altered following successful transplantation of islet

Condition Intervention Phase
Type 1 Diabetes Mellitus
Procedure: Islet Transplantation
Phase II

MedlinePlus related topics: Diabetes Diabetes Type 1 Islet Cell Transplantation
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: Islet Cell Transplantation Alone and CD34+ Enriched Donor Bone Marrow Cell Infusion in Patients With Type 1 Diabetes Mellitus; Steroid Free Regimen

Further study details as provided by University of Miami:

Primary Outcome Measures:
  • The achievement of persistent islet function following cessation of immunosuppression.
  • A reduction or absence of rejection episodes
  • The induction of multilineage chimerism

Secondary Outcome Measures:
  • Insulin independence or reduction in exogenous insulin requirements (partial graft function), as evidenced by basal C-peptide greater than 0.5 ng/ml prior to weaning of immunosuppression;
  • Improvement in metabolic control as evidenced by improvement in:
  • HbA1C (should be < 6.5%),
  • Mean amplitude of glycemic excursions (MAGE),
  • Mean glucose meter readings,
  • CGMS (continuous glucose monitoring system)
  • elimination or reduction in the incidence of hypoglycemic coma or unawareness;
  • Improvement in or decreased progression of microvascular, macrovascular and neuropathic complications of diabetes.

Estimated Enrollment: 6
Study Start Date: December 2000
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: Islet Transplantation
    Islet transplantation
Detailed Description:

In our current protocol (IRB #2000/0024) the immunosuppressive regimen, comprised of induction with daclizumab and maintenance therapy with sirolimus and tacrolimus, has been combined with the infusion of CD34+ enriched donor bone marrow stem cells in an attempt to create a chimeric state and hence induce donor tolerance. This strategy was tested by evaluating graft survival following the removal of all immunosuppressive medication after one year.

  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. Untreated proliferative diabetic retinopathy;
  2. HbA1C > 12%;
  3. Insulin requirement > 1.0u/kg/d
  4. Stimulated or basal C-peptide > 0.3 ng/ml
  5. Creatinine clearance < 60 and/or serum creatinine consistently > 1.5mg/dl;
  6. Macroalbuminuria > 300mg albumin in 24 hours
  7. Presence of panel reactive antibodies > 20%;
  8. Previous/concurrent organ transplantation (except failed islet cell transplantation);
  9. Any medical condition requiring chronic use of steroids;
  10. Malignancy or previous malignancy (except non-melanomatous skin cancer);
  11. X-ray evidence of pulmonary infection;
  12. Active infections;
  13. Positive tuberculin test (unless proof of adequate treatment for latent tuberculosis can be provided)
  14. Active peptic ulcer disease,
  15. Gall stones and/or portal hypertension and/or hemangioma on liver ultrasound;
  16. Serological evidence of HIV, HBV (HBsAg+ and/or HBcAb+ and/or HBsAb+ without evidence of vaccination), HTLV-1 or HCV;
  17. Negative serology for Epstein Barr virus (EBV) or evidence of acute infection (IgM>IgG);
  18. Abnormal liver function test;
  19. Anemia (hemoglobin <12.0 g/dl);
  20. Hyperlipidemia (fasting total cholesterol >240mg/dl and/or fasting triglycerides >200mg/dl and/or fasting LDL cholesterol>140mg/dl);
  21. Body Mass Index above 26 and/or weight >80kg;
  22. Prostate specific antigen (PSA) > 4 ng/ml;
  23. Unstable cardiovascular status (including positive stress echocardiography if >age 35);
  24. Active alcohol or substance abuse;
  25. 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);
  26. Positive pregnancy test or intent for future pregnancy, or male subject's intent to procreate.
  27. Any condition or any circumstances that makes it unsafe to undergo an islet cell transplant.
  28. History of previous transplant or previous bone marrow infusion.
  29. Persistent leucopenia (white blood cell count <3,000/mm3
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00315614

Contacts
Contact: Rodolfo Alejandro, MD 305-243-5324
Contact: Camillo Ricordi, MD 305-243-6913

Locations
United States, Florida
Diabetes Research Institute Recruiting
Miami, Florida, United States, 33136
Contact: Rodolfo Alejandro, MD     305-243-5324     ralejand@med.miami.edu or islet@med.miami.edu    
Contact: Camillo Ricordi, MD     305-243-6913     islet@med.miami.edu    
Sub-Investigator: Camillo Ricordi, MD            
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: Rodolfo Alejandro, MD Diabetes Research Institute University of Miami
  More Information

Diabetes Research Institute web site  This link exits the ClinicalTrials.gov site

Publications indexed to this study:
Responsible Party: Diabetes Research Insititute, University of Miami ( Rodolfo Alejandro, MD )
Study ID Numbers: 2000/0024
Study First Received: April 14, 2006
Last Updated: June 19, 2008
ClinicalTrials.gov Identifier: NCT00315614  
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
Islet Transplantation

Study placed in the following topic categories:
Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Diabetes Mellitus
Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders

Additional relevant MeSH terms:
Immune System Diseases

ClinicalTrials.gov processed this record on January 16, 2009