Clinical trial NCT00437398: Islet Transplantation for Type 1 Diabetes Mellitus
Official title: Islet Transplantation for Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Type 1 Diabetes Mellitus
Keywords: hypoglycemic unawareness
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Center for Research Resources (NCRR)
First posted: 2007-02-21
Enrollment: 2
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: The complex program of insulin replacement for type 1 diabetes that is current clinical standard of care is difficult to implement for long periods of time, associated with an increased risk of severe hypoglycemia and implemented by less than 50 % of the population of such patients. Outcomes of transplantation of isolated human islets have substantially improved and been performed at about 40 institutions around the world. We are proposing a clinical phase 1/phase 2 study of islet transplantation alone evaluating safety and efficacy in five patients with type 1 diabetes. Islet isolation from deceased donor pancreases will be performed at the Mayo Rochester Islet Isolation facility and islets infused by Interventional Radiology into the portal venous system. Following islet infusion, patients will be hospitalized for 48 hours in the General Clinical Research Center (GCRC) or at the Rochester Methodist Hospital. Multiple safety and efficacy outcomes will be followed on multiple occasions during the first year and periodically thereafter.


Eligibility criteria: Inclusion Criteria:

* Duration of diabetes: 5 years or more
* Type 1 diabetes with C-peptide \< 200 pmol/L and a simultaneous plasma glucose between 60 and 250 mg/dl
* Complex insulin program supervised by an endocrinologist for at least 6 months
* Hypoglycemic unawareness diagnosed using Clarke Awareness Questionnaire
* Body weight \< 70 kg
* Body Mass Index \< 30 kg/m\^2
* Insulin requirement \< 40 units/day by multiple daily injections or \< 30 units /day by external insulin pump or \< 0.6 unit/kg/day with a HbA1c \< 7.0 % ( Normal \< 6 %)
* No overt cardiovascular disease
* No laser treatment for retinopathy
* Retinopathy diagnosed by ophthalmologist to be stable and requiring no further evaluation for at least one year
* Women of child bearing age will have a negative pregnancy test at screening and time of trial initiation
* Women enrolled in the trial should be willing to practice birth control while on immunosuppression
* No psychologic issues that would interfere with adherence to safe clinical practice
* Blood type (ABO) compatibility
* No evidence of chronic liver disease (aspartate aminotransferase (AST) \< 2.5 times normal, alanine aminotransferase (ALT) \< 2.5 times normal, international normalized ratio (INR) \< 1.4, No evidence of fatty liver on abdominal ultrasound.

Exclusion Criteria:

* Ongoing infection
* Ongoing alcohol or drug abuse
* Clinical portal hypertension
* Gall stones
* Liver hemangioma on ultrasound interfering with islet infusion
* Lack of updated immunization
* Unstable cardiovascular status as defined by:

  1. Myocardial infarction/acute coronary syndrome in last year
  2. Significant coronary atherosclerosis on angiography
  3. Active ischemia at evaluation
* Pre-trial low-density lipoprotein (LDL) cholesterol \> 100 and triglycerides \> 200 mg/dl with or without lipid lowering therapy
* Active peptic ulcer disease
* Previous organ transplantation except islet transplantation
* Negative serology for Epstein-Barr Virus (EBV) or ongoing acute EBV infection
* Previous malignancy unless

  1. 5 years ago
  2. basal cell cancer
  3. squamous cell cancer
* Requiring steroid therapy for any reason
* Positive Purified Protein Derivative (PPD - Tuberculosis Skin Test)
* Serological evidence of HIV, Hepatitis C or Hepatitis B
* Chronic anemia
* Single Antigen B (SAB) normalized value \>1500
* Renal disease

  1. Iothalamate clearance \< 70 cc/min
  2. 24 hour urine protein \> 500 mg/24 hours

Primary outcomes:
measure: Mean Number of Hypoglycemic Events After Transplant
timeFrame: 3, 6, 9, and 12 months since islet transplantation
Secondary outcomes:
measure: Mean Glycated Hemoglobin (HbA1c) Since Transplant
timeFrame: 3, 6, 9, and 12 months since islet transplantation
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Yogish C. Kudva, M.B.B.S.
role: PRINCIPAL_INVESTIGATOR
References: