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

NCT00285233 | Completed Phase 1 DMC

• 1 other identifier: 0006M55241
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes; Hypoglycemia

Outcome Measures

Primary Outcomes (5)

• 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

• Assess liver laboratory tests during the first year following intraportal islet allotransplantation.

  1 yr

• Assess the incidence, type, and severity of islet transplant-related infectious complications during the first year posttransplant.

  1 year

• Assess the proportion of recipients who develop alloantibodies directed at donor alloantigens during the first year posttransplant.

  1 year

• 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

Secondary Outcomes (5)

• 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

• Assess the proportion of type 1 diabetic islet allograft recipients with full and partial alloislet function at one year post transplant.

  1 year

• Assess the glycemic control, insulin secretory responses, and the glucose disposal rate during the first year posttransplant.

  1 year

• 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

• 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

Study Arms (1)

1

EXPERIMENTAL

Biological: Allogeneic islets of Langerhans transplant

Interventions

Allogeneic islets of Langerhans transplant BIOLOGICAL

Allogeneic islets of Langerhans transplant

Also known as: Islet transplant

1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Minnesota: lead
• Roche Pharma AG: collaborator
• Juvenile Diabetes Research Foundation: collaborator

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related 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. doi: 10.1001/jama.293.7.830.

  PMID: 15713772 RESULT

Related Links

• Diabetes Institute for Immunology and Transplantation - U of M

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Bernhard J. Hering, M.D.

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2006
• First Posted: February 1, 2006
• Study Start: September 1, 2000
• Primary Completion: September 1, 2004
• Study Completion: March 1, 2005
• Last Updated: August 2, 2012

Record last verified: 2012-07

Locations

US (1)