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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Belatacept and Raptiva

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Allogenic pancreatic islet transplant using belatacept and raptiva	Drug: Belatacept and Raptiva; immunosuppressant agent to prevent rejection in transplant recipients; Other Names: immunosuppressant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lnsulin independence	improved glycemic control	monthly

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Juvenile Diabetes Research Foundation
• Investigators: Principal Investigator: Peter G Stock, M.D., Ph.D., University of California, San Francisco; Principal Investigator: Andrew Posselt, M.D., Ph.D., University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2007
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: July 12, 2007
• First Submitted That Met QC Criteria: July 13, 2007
• First Posted (Estimate): July 16, 2007

Study Record Updates

• Last Update Posted (Actual): May 6, 2020
• Last Update Submitted That Met QC Criteria: April 30, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept; Immunosuppressive Agents
• Other Study ID Numbers: 39-42C

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No