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Islet Cell Transplantation Alone and CD34+ Donor Bone Marrow Cell Infusion in Type 1 Diabetes Mellitus

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Rodolfo Alejandro, University of Miami
ClinicalTrials.gov Identifier:
NCT00315614
First received: April 14, 2006
Last updated: April 16, 2014
Last verified: March 2014

April 14, 2006
April 16, 2014
December 2000
December 2010   (final data collection date for primary outcome measure)
  • The Achievement of Persistent Islet Function Following Cessation of Immunosuppression. [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • A Reduction or Absence of Rejection Episodes [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • The Induction of Multilineage Chimerism [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • The achievement of persistent islet function following cessation of immunosuppression.
  • A reduction or absence of rejection episodes
  • The induction of multilineage chimerism
Complete list of historical versions of study NCT00315614 on ClinicalTrials.gov Archive Site
  • 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; [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • Improvement in Metabolic Control as Evidenced by Improvement in: [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • HbA1C (Should be < 6.5%), [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • Mean Amplitude of Glycemic Excursions (MAGE), [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • Mean Glucose Meter Readings, [ Time Frame: for the duration of islet graft function ] [ Designated as safety issue: No ]
  • CGMS (Continuous Glucose Monitoring System) [ 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 ]
  • 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.
Not Provided
Not Provided
 
Islet Cell Transplantation Alone and CD34+ Donor Bone Marrow Cell Infusion in Type 1 Diabetes Mellitus
Islet Cell Transplantation Alone and CD34+ Enriched Donor Bone Marrow Cell Infusion in Patients With Type 1 Diabetes Mellitus; Steroid Free Regimen

SPECIFIC AIMS:

  • To reverse hyperglycemia and insulin dependency in patients with Type 1 diabetes mellitus by islet cell transplantation.
  • 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.
  • To assess long-term function of successful islet cell transplants in patients with Type 1 diabetes mellitus.
  • To determine whether the natural history of the microvascular, macrovascular and neuropathic complications are altered following successful transplantation of islet

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Type 1 Diabetes Mellitus
Drug: Islet Transplantation
Islet transplantation
Other Names:
  • Islet
  • type 1 DM
  • Bone marrow
Experimental: islet transplant and CD34 Bone Marrow
islet transplantation and infusion of CD34 enriched Bone Marrow cells.
Intervention: Drug: Islet Transplantation
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
3
December 2010
December 2010   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00315614
2000/0024, R01DK056953
Yes
Rodolfo Alejandro, University of Miami
University of Miami
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Rodolfo Alejandro, MD Diabetes Research Institute University of Miami
University of Miami
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP