Delayed Mycophenolate Mofetil in Single-Donor Islet Allotransplantation in Type 1 Diabetes

Type 1 Diabetes Clinical Trial

Official title:

An Open-label Pilot Study of Delayed Mycophenolate Mofetil Instead of Tacrolimus Combined With Anti-thymocyte Globulin, Daclizumab, Etanercept, and Sirolimus in Single-donor, Solitary Islet Allograft Recipients With Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00285233
• Other study ID #: 0006M55241
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 30, 2006
• Last updated: July 31, 2012
• Start date: September 2000
• Est. completion date: March 2005

Study information

• Verified date: July 2012
• Source: University of Minnesota - Clinical and Translational Science Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to assess the safety and efficacy of islet allotransplantation for the reestablishment of stable glycemic control in patients with type 1 diabetes, using anti-thymocyte globulin induction immunosuppression with sirolimus, mycophenolate mofetil and low dose tacrolimus maintenance immunosuppression.

Description:

To assess the safety and efficacy of a new single-donor islet allotransplant protocol focusing on minimization of ischemic damage by the two-layer pancreas preservation technique, attenuation of posttransplant nonspecific inflammatory responses by etanercept and anti-thymocyte globulin, deletion/inactivation of autoreactive T cells by anti-thymocyte globulin and daclizumab induction immunotherapy, and potent yet non-diabetogenic maintenance immunosuppression with sirolimus and delayed mycophenolate mofetil instead of tacrolimus for the reestablishment of stable glycemic control in recipients with type 1 diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: March 2005
• Est. primary completion date: September 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Primary islet allotransplant

2. Type 1 diabetes mellitus, complicated by at least one of the following situations that persist despite intensive efforts in close cooperation with their diabetes care team:

1. Metabolic lability/instability;

2. Reduced awareness of hypoglycemia;

3. Persistently poor glucose control (as defined by HgbA1c>10% at the end of six months of intensive management efforts with the diabetes care team);

4. Progressive secondary complications.

3. Age 18 and older

4. Able to give written informed consent

Exclusion Criteria:

1. Known hypersensitivity to rabbit proteins.

2. Presence of history of panel-reactive anti-HLA antibodies (>10%).

3. Insufficient cardiovascular reserve.

4. Creatinine clearance <60 mL/min/m2.

5. Portal hypertension, abnormal liver enzyme tests, or history of significant liver disease.

6. History of malignancy within 5 years.

7. Active peptic ulcer disease.

8. Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications.

9. Pregnancy or breast-feeding.

10. Active infections.

11. Serological evidence of infection with HIV, or HBsAg or HCVAb positive within the previous 12 months prior to transplantation.

12. Negative screen for Epstein-Barr Virus (EBV) by an EBNA method

13. Evidence of infiltrate, cavitation, or consolidation on chest x-ray during pre-study screening.

14. Schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medications.

15. Ongoing substance abuse; drug or alcohol.

16. Recent history of noncompliance.

17. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Biological:
• Allogeneic islets of Langerhans transplant
Allogeneic islets of Langerhans transplant

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
University of Minnesota - Clinical and Translational Science Institute	Juvenile Diabetes Research Foundation, Roche Pharma AG

Country where clinical trial is conducted

United States, 

References & Publications (1)

Hering BJ, Kandaswamy R, Ansite JD, Eckman PM, Nakano M, Sawada T, Matsumoto I, Ihm SH, Zhang HJ, Parkey J, Hunter DW, Sutherland DE. Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. JAMA. 2005 Feb 16;293(7):830-5. Errat — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assess the incidence and severity of hypoglycemia in type 1 diabetic subjects receiving an islet allotransplant and immunotherapy during the first year posttransplant.		1 year	Yes
Primary	Assess liver laboratory tests during the first year following intraportal islet allotransplantation.		1 yr	Yes
Primary	Assess the incidence, type, and severity of islet transplant-related infectious complications during the first year posttransplant.		1 year	Yes
Primary	Assess the proportion of recipients who develop alloantibodies directed at donor alloantigens during the first year posttransplant.		1 year	Yes
Primary	Monitor the incidence, timing, and severity of adverse events as well as their relationship to the islet transplant procedure and additional protocol-regulated treatment products during the first year after islet transplantation.		1 year	Yes
Secondary	Assess the proportion of type 1 diabetic subjects receiving delayed mycophenolate mofetil instead of tacrolimus who achieve insulin independence in the first year after transplantation of allogeneic islets.		1 year	No
Secondary	Assess the proportion of type 1 diabetic islet allograft recipients with full and partial alloislet function at one year post transplant.		1 year	No
Secondary	Assess the glycemic control, insulin secretory responses, and the glucose disposal rate during the first year posttransplant.		1 year	No
Secondary	Effect of donor age, pretransplant islet insulin secretory response, # of transplanted islet equivalents, # of transplanted beta cells, pretransplant insulin action, recipient BMI and immunosuppressive therapy on safety and efficacy.		1 year	No
Secondary	Assess, in a selected group of islet allotransplant recipients, the autoimmune and alloimmune responses to transplanted islets at intervals during the first year posttransplant.		1 year	No