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

• ClinicalTrials.gov Identifier: NCT00501709
• Recruitment Status: Completed
• First Posted: July 16, 2007
• Last Update Posted: May 6, 2020
• Sponsor: University of California, San Francisco
• Collaborator: Juvenile Diabetes Research Foundation
• Information provided by (Responsible Party): University of California, San Francisco

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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Drug: Belatacept and Raptiva	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prevention of Autoimmune Destruction and Rejection of Human Pancreatic Islets Following Transplantation for Insulin Dependent Diabetes Mellitus
• Actual Study Start Date: February 2007
• Actual Primary Completion Date: December 2016
• Actual Study Completion Date: December 2016

Arms and Interventions

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 Name: immunosuppressant

Outcome Measures

Primary Outcome Measures :

1. lnsulin independence [ Time Frame: monthly ]
   improved glycemic control

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, California

University of California, San Francisco

San Francisco, California, United States, 94143

Sponsors and Collaborators

University of California, San Francisco

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

More Information

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00501709
• Other Study ID Numbers: 39-42C
• First Posted: July 16, 2007
• Last Update Posted: May 6, 2020
• Last Verified: April 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Abatacept; Immunosuppressive Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents