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

This study has been terminated.
(We did not achieve a tolerogenic profile. Subjects withdrew from protocol and enrolled in other islet transplant trials.)
Sponsor:
Collaborators:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Diabetes Research Institute Foundation
Information provided by (Responsible Party):
Rodolfo Alejandro, University of Miami
ClinicalTrials.gov Identifier:
NCT00315614
First received: April 14, 2006
Last updated: March 29, 2017
Last verified: March 2017
April 14, 2006
March 29, 2017
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 ]
    Immunosuppression was never discontinued. Patients elected to move to other trials to receive additional islet infusions. Since immunosuppression was never discontinued we were not able to evaluate the primary endpoint.
  • A Reduction or Absence of Rejection Episodes [ Time Frame: for the duration of islet graft function ]
    Number of rejection episodes after transplantation. Immunosuppression was never discontinued. Patients elected to move to other trials to receive additional islet infusions. Since immunosuppression was never discontinued we were not able to evaluate the primary endpoint.
  • 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
  • Number of Subjects With Basal C-peptide Greater Than 0.5 ng/ml [ Time Frame: for the duration of islet graft function ]
    Number of subjects with basal C-peptide greater than 0.5 ng/ml prior to weaning of immunosuppression;
  • Number of Subjects With Reduction of Severe Hypoglycemia and Improvement in Hypoglycemia Awareness [ Time Frame: for the duration of islet graft function ]
    Number of subjects with reduction of episodes of severe hypoglycemia and the presence of awareness of hypoglycemia
  • 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
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Type 1 Diabetes Mellitus
Biological: Islet Transplantation and Bone Marrow
Islet transplantation and CD34 Bone Marrow infusion in subjects with type 1 diabetes.
Other Names:
  • Islet
  • type 1 DM
  • Bone marrow
Experimental: Islet Transplantation and Bone Marrow
Administration of islets and infusion of CD34 enriched Bone Marrow cells in subjects with type 1 diabetes, impaired awareness of hypoglycemia and severe hypoglycemia.
Intervention: Biological: Islet Transplantation and Bone Marrow
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
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
Sexes Eligible for Study: All
18 Years to 65 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00315614
2000/0024
R01DK056953 ( US NIH Grant/Contract Award Number )
Yes
Not Provided
No
Single arm few subjects.
Rodolfo Alejandro, University of Miami
University of Miami
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Diabetes Research Institute Foundation
Principal Investigator: Rodolfo Alejandro, MD Diabetes Research Institute University of Miami
University of Miami
March 2017

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