Islet Transplantation for Type 1 Diabetes Mellitus

This study has been terminated.
(The study was terminated early due to difficulty in recruiting subjects, and ran short of funds.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Yogish C. Kudva, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00437398
First received: February 20, 2007
Last updated: April 18, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes Mellitus
Biological: Islet Transplant
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Islet Transplantation for Type 1 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Mean Number of Hypoglycemic Events After Transplant [ Time Frame: 3, 6, 9, and 12 months since islet transplantation ] [ Designated as safety issue: Yes ]
    Hypoglycemia is an abnormally diminished content of glucose in the blood.


Secondary Outcome Measures:
  • Mean Glycated Hemoglobin (HbA1c) Since Transplant [ Time Frame: 3, 6, 9, and 12 months since islet transplantation ] [ Designated as safety issue: Yes ]
    HbA1c is a lab test that shows the average level of blood sugar (glucose) over the previous 3 months. It shows how well the subject is controlling his/her diabetes.


Enrollment: 2
Study Start Date: July 2006
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Islet Transplant
Subjects will receive standard intraportal transplantation or portal venous system infusion via laparotomy of purified pancreatic islets.
Biological: Islet Transplant
Purified pancreatic islets

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00437398

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Yogish C. Kudva, M.B.B.S. Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Yogish C. Kudva, MBBS, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00437398     History of Changes
Other Study ID Numbers: 06-003564, UL1RR024150
Study First Received: February 20, 2007
Results First Received: March 5, 2013
Last Updated: April 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
hypoglycemic unawareness

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on October 29, 2014