Clinical trial NCT00501709: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Type 1 Diabetes
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Juvenile Diabetes Research Foundation
First posted: 2007-07-16
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: lnsulin independence
timeFrame: monthly
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Peter G Stock, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Andrew Posselt, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: