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

Type 1 Diabetes Mellitus Clinical Trial

Official title:

Islet Cell Transplantation Alone and CD34+ Enriched Donor Bone Marrow Cell Infusion in Patients With Type 1 Diabetes Mellitus; Steroid Free Regimen

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00315614
• Other study ID #: 2000/0024
• Secondary ID: R01DK056953
• Status: Terminated
• Phase: Phase 2
• First received: April 14, 2006
• Last updated: March 29, 2017
• Start date: December 2000
• Est. completion date: December 2010

Study information

• Verified date: March 2017
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Biological:
• Islet Transplantation and Bone Marrow
Islet transplantation and CD34 Bone Marrow infusion in subjects with type 1 diabetes.

Locations

Country	Name	City	State
United States	Diabetes Research Institute	Miami	Florida

Sponsors (3)

Lead Sponsor	Collaborator
University of Miami	Diabetes Research Institute Foundation, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Achievement of Persistent Islet Function Following Cessation of Immunosuppression.	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.	for the duration of islet graft function
Primary	A Reduction or Absence of Rejection Episodes	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.	for the duration of islet graft function
Secondary	Number of Subjects With Basal C-peptide Greater Than 0.5 ng/ml	Number of subjects with basal C-peptide greater than 0.5 ng/ml prior to weaning of immunosuppression;	for the duration of islet graft function
Secondary	Number of Subjects With Reduction of Severe Hypoglycemia and Improvement in Hypoglycemia Awareness	Number of subjects with reduction of episodes of severe hypoglycemia and the presence of awareness of hypoglycemia	for the duration of islet graft function

External Links

•   Diabetes Research Institute web site