We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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:
ClinicalTrials.gov Identifier:
NCT00315614
First Posted: April 18, 2006
Last Update Posted: April 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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
  Purpose

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

Condition Intervention Phase
Type 1 Diabetes Mellitus Biological: Islet Transplantation and Bone Marrow Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Islet Cell Transplantation Alone and CD34+ Enriched Donor Bone Marrow Cell Infusion in Patients With Type 1 Diabetes Mellitus; Steroid Free Regimen

Resource links provided by NLM:


Further study details as provided by Rodolfo Alejandro, University of Miami:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 3
Study Start Date: December 2000
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00315614


Locations
United States, Florida
Diabetes Research Institute
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Diabetes Research Institute Foundation
Investigators
Principal Investigator: Rodolfo Alejandro, MD Diabetes Research Institute University of Miami
  More Information

Additional Information:
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: NCT00315614     History of Changes
Other Study ID Numbers: 2000/0024
R01DK056953 ( U.S. NIH Grant/Contract )
First Submitted: April 14, 2006
First Posted: April 18, 2006
Results First Submitted: December 20, 2013
Results First Posted: February 10, 2014
Last Update Posted: April 4, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Single arm few subjects.

Keywords provided by Rodolfo Alejandro, University of Miami:
Islet Transplantation

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