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

Primary Purpose

Type 1 Diabetes, Hypoglycemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allogeneic islets of Langerhans transplant
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Primary islet allotransplant 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: Metabolic lability/instability; Reduced awareness of hypoglycemia; Persistently poor glucose control (as defined by HgbA1c>10% at the end of six months of intensive management efforts with the diabetes care team); Progressive secondary complications. Age 18 and older Able to give written informed consent Exclusion Criteria: Known hypersensitivity to rabbit proteins. Presence of history of panel-reactive anti-HLA antibodies (>10%). Insufficient cardiovascular reserve. Creatinine clearance <60 mL/min/m2. Portal hypertension, abnormal liver enzyme tests, or history of significant liver disease. History of malignancy within 5 years. Active peptic ulcer disease. Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications. Pregnancy or breast-feeding. Active infections. Serological evidence of infection with HIV, or HBsAg or HCVAb positive within the previous 12 months prior to transplantation. Negative screen for Epstein-Barr Virus (EBV) by an EBNA method Evidence of infiltrate, cavitation, or consolidation on chest x-ray during pre-study screening. Schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medications. Ongoing substance abuse; drug or alcohol. Recent history of noncompliance. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.

Sites / Locations

  • University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Outcomes

Primary Outcome Measures

Assess the incidence and severity of hypoglycemia in type 1 diabetic subjects receiving an islet allotransplant and immunotherapy during the first year posttransplant.
Assess liver laboratory tests during the first year following intraportal islet allotransplantation.
Assess the incidence, type, and severity of islet transplant-related infectious complications during the first year posttransplant.
Assess the proportion of recipients who develop alloantibodies directed at donor alloantigens during the first year posttransplant.
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.

Secondary Outcome Measures

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.
Assess the proportion of type 1 diabetic islet allograft recipients with full and partial alloislet function at one year post transplant.
Assess the glycemic control, insulin secretory responses, and the glucose disposal rate during the first year posttransplant.
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.
Assess, in a selected group of islet allotransplant recipients, the autoimmune and alloimmune responses to transplanted islets at intervals during the first year posttransplant.

Full Information

First Posted
January 30, 2006
Last Updated
July 31, 2012
Sponsor
University of Minnesota
Collaborators
Roche Pharma AG, Juvenile Diabetes Research Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00285233
Brief Title
Delayed Mycophenolate Mofetil in Single-Donor Islet Allotransplantation in Type 1 Diabetes
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
September 2000 (undefined)
Primary Completion Date
September 2004 (Actual)
Study Completion Date
March 2005 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
Collaborators
Roche Pharma AG, Juvenile Diabetes Research Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes, Hypoglycemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Allogeneic islets of Langerhans transplant
Other Intervention Name(s)
Islet transplant
Intervention Description
Allogeneic islets of Langerhans transplant
Primary Outcome Measure Information:
Title
Assess the incidence and severity of hypoglycemia in type 1 diabetic subjects receiving an islet allotransplant and immunotherapy during the first year posttransplant.
Time Frame
1 year
Title
Assess liver laboratory tests during the first year following intraportal islet allotransplantation.
Time Frame
1 yr
Title
Assess the incidence, type, and severity of islet transplant-related infectious complications during the first year posttransplant.
Time Frame
1 year
Title
Assess the proportion of recipients who develop alloantibodies directed at donor alloantigens during the first year posttransplant.
Time Frame
1 year
Title
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
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.
Time Frame
1 year
Title
Assess the proportion of type 1 diabetic islet allograft recipients with full and partial alloislet function at one year post transplant.
Time Frame
1 year
Title
Assess the glycemic control, insulin secretory responses, and the glucose disposal rate during the first year posttransplant.
Time Frame
1 year
Title
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.
Time Frame
1 year
Title
Assess, in a selected group of islet allotransplant recipients, the autoimmune and alloimmune responses to transplanted islets at intervals during the first year posttransplant.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Primary islet allotransplant 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: Metabolic lability/instability; Reduced awareness of hypoglycemia; Persistently poor glucose control (as defined by HgbA1c>10% at the end of six months of intensive management efforts with the diabetes care team); Progressive secondary complications. Age 18 and older Able to give written informed consent Exclusion Criteria: Known hypersensitivity to rabbit proteins. Presence of history of panel-reactive anti-HLA antibodies (>10%). Insufficient cardiovascular reserve. Creatinine clearance <60 mL/min/m2. Portal hypertension, abnormal liver enzyme tests, or history of significant liver disease. History of malignancy within 5 years. Active peptic ulcer disease. Severe unremitting diarrhea or other gastrointestinal disorders potentially interfering with the ability to absorb oral medications. Pregnancy or breast-feeding. Active infections. Serological evidence of infection with HIV, or HBsAg or HCVAb positive within the previous 12 months prior to transplantation. Negative screen for Epstein-Barr Virus (EBV) by an EBNA method Evidence of infiltrate, cavitation, or consolidation on chest x-ray during pre-study screening. Schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medications. Ongoing substance abuse; drug or alcohol. Recent history of noncompliance. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bernhard J. Hering, M.D.
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
15713772
Citation
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. doi: 10.1001/jama.293.7.830. Erratum In: JAMA. 2005 Apr 6;293(13):1594.
Results Reference
result
Links:
URL
http://www.diabetesinstitute.org
Description
Diabetes Institute for Immunology and Transplantation - U of M

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

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