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Prevention of Autoimmune Destruction and Rejection of Human Pancreatic Islets Following Transplantation for Insulin Dependent Diabetes Mellitus

Primary Purpose

Type 1 Diabetes

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Belatacept and Raptiva
Sponsored by
University of California, San Francisco
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 SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Type 1 Diabetes
  • Metabolic lability/instability characterized by hypoglycemia or ketoacidosis(>2 hospital admissions in the previous year), erratic glucose profiles(MAGE >120mg/dL), or disruption in lifestyle(danger to life, self or others). Reduced awareness of hypoglycemia or > 1 episode in the last 1.5 years of severe hypoglycemia.
  • Persistently poor glucose control (as defined by HgbA1c>10% at the end of six months of intensive management efforts with diabetes care team.

  • Progressive secondary complications as defined by

    • a new diagnosis by an ophthalmologist of proliferative retinopathy or clinically significant macular edema or therapy with photocoagulation during the last year; or
    • urinary albumin excretion rate >300mg/day but proteinuria <3g/day; or
    • symptomatic autonomic neuropathy (as defined by postural hypotension in the setting of euvolemia, gastroparesis or diarrhea attributed to diabetic neuropathy, or neuropathic bladder as diagnosed by an urologist)

Exclusion Criteria:

  • Patient weighs more than 80kg or body mass index BMI>28
  • Patient's insulin requirement is >55 Units/day.
  • Current use of immunosuppressive agents.
  • History of malignancy within 10 years (except for adequately treated basal or squamous cell CA of the skin).
  • Active peptic ulcer disease.
  • Severe unremitting diarrhea or other GI disorders potentially interfering with the ability to absorb oral medications.
  • Untreated proliferative retinopathy.
  • Pregnancy or breastfeeding.
  • Female subjects not post-menopausal or surgically sterile, or not using an acceptable method or contraception.
  • Active infections.
  • Major ongoing psychiatric illness.
  • Ongoing substance abuse, drug or alcohol; or recent history of noncompliance.
  • Portal hypertension or history of significant liver disease.
  • Lymphopenia (<1000/ul) or leukopenia (<3000 total leukocytes/ul) or an absolute CD4 count <500/ul.
  • Presence or history of panel-reactive anti-HLA antibody >20%.
  • Evidence of acute EBV infection (IgM>IgG) OR no serologic evidence of previous exposure to EBV (IgG>IgM).
  • Serologic evidence of infection with HIV or HbsAg or HCV Ab positive.
  • Creatinine clearance <60ml/min/m2.
  • Positive lymphocytoxic cross-match using donor lymphocytes and serum

Sites / Locations

  • University of California, San Francisco

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

Allogenic pancreatic islet transplant using belatacept and raptiva

Outcomes

Primary Outcome Measures

lnsulin independence
improved glycemic control

Secondary Outcome Measures

Full Information

First Posted
July 12, 2007
Last Updated
April 30, 2020
Sponsor
University of California, San Francisco
Collaborators
Juvenile Diabetes Research Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00501709
Brief Title
Prevention of Autoimmune Destruction and Rejection of Human Pancreatic Islets Following Transplantation for Insulin Dependent Diabetes Mellitus
Official Title
Prevention of Autoimmune Destruction and Rejection of Human Pancreatic Islets Following Transplantation for Insulin Dependent Diabetes Mellitus
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
February 2007 (Actual)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Juvenile Diabetes Research Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Pancreatic islets are the part of the pancreas that produce insulin and help control the blood sugar. This study aims to improve islet transplantation as a treatment for Type 1 Diabetes by using a new combination of immunosuppressive drugs that have been successful in treating other autoimmune diseases and in preventing kidney transplant rejection.
Detailed Description
The primary objective of these studies is to assess the efficacy and safety of allogeneic pancreatic islet transplantation in the treatment of type I diabetes mellitus. A secondary study objective is to evaluate the efficacy of various immunosuppressive protocols and agents in preventing autoimmune destruction and rejection of allogeneic islet transplants. A tertiary objective is to determine the safety and efficacy of allogeneic pancreatic islet transplantation in patients who have received another organ transplant such as a kidney or liver.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
Allogenic pancreatic islet transplant using belatacept and raptiva
Intervention Type
Drug
Intervention Name(s)
Belatacept and Raptiva
Other Intervention Name(s)
immunosuppressant
Intervention Description
immunosuppressant agent to prevent rejection in transplant recipients
Primary Outcome Measure Information:
Title
lnsulin independence
Description
improved glycemic control
Time Frame
monthly

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Type 1 Diabetes Metabolic lability/instability characterized by hypoglycemia or ketoacidosis(>2 hospital admissions in the previous year), erratic glucose profiles(MAGE >120mg/dL), or disruption in lifestyle(danger to life, self or others). Reduced awareness of hypoglycemia or > 1 episode in the last 1.5 years of severe hypoglycemia. Persistently poor glucose control (as defined by HgbA1c>10% at the end of six months of intensive management efforts with diabetes care team. Progressive secondary complications as defined by a new diagnosis by an ophthalmologist of proliferative retinopathy or clinically significant macular edema or therapy with photocoagulation during the last year; or urinary albumin excretion rate >300mg/day but proteinuria <3g/day; or symptomatic autonomic neuropathy (as defined by postural hypotension in the setting of euvolemia, gastroparesis or diarrhea attributed to diabetic neuropathy, or neuropathic bladder as diagnosed by an urologist) Exclusion Criteria: Patient weighs more than 80kg or body mass index BMI>28 Patient's insulin requirement is >55 Units/day. Current use of immunosuppressive agents. History of malignancy within 10 years (except for adequately treated basal or squamous cell CA of the skin). Active peptic ulcer disease. Severe unremitting diarrhea or other GI disorders potentially interfering with the ability to absorb oral medications. Untreated proliferative retinopathy. Pregnancy or breastfeeding. Female subjects not post-menopausal or surgically sterile, or not using an acceptable method or contraception. Active infections. Major ongoing psychiatric illness. Ongoing substance abuse, drug or alcohol; or recent history of noncompliance. Portal hypertension or history of significant liver disease. Lymphopenia (<1000/ul) or leukopenia (<3000 total leukocytes/ul) or an absolute CD4 count <500/ul. Presence or history of panel-reactive anti-HLA antibody >20%. Evidence of acute EBV infection (IgM>IgG) OR no serologic evidence of previous exposure to EBV (IgG>IgM). Serologic evidence of infection with HIV or HbsAg or HCV Ab positive. Creatinine clearance <60ml/min/m2. Positive lymphocytoxic cross-match using donor lymphocytes and serum
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter G Stock, M.D., Ph.D.
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Andrew Posselt, M.D., Ph.D.
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Prevention of Autoimmune Destruction and Rejection of Human Pancreatic Islets Following Transplantation for Insulin Dependent Diabetes Mellitus

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