Islet Transplantation for Type 1 Diabetes Mellitus

NCT00437398 | Terminated Phase 1 Results DMC

• 2 other identifiers: 06-003564UL1RR024150
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes Mellitus

Keywords

hypoglycemic unawareness

Outcome Measures

Primary Outcomes (1)

• Mean Number of Hypoglycemic Events After Transplant

  Hypoglycemia is an abnormally diminished content of glucose in the blood.

  3, 6, 9, and 12 months since islet transplantation

Secondary Outcomes (1)

• Mean Glycated Hemoglobin (HbA1c) Since Transplant

  3, 6, 9, and 12 months since islet transplantation

Study Arms (1)

Islet Transplant

EXPERIMENTAL

Subjects will receive standard intraportal transplantation or portal venous system infusion via laparotomy of purified pancreatic islets.

Biological: Islet Transplant

Interventions

Islet Transplant BIOLOGICAL

Purified pancreatic islets

Islet Transplant

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Myocardial infarction/acute coronary syndrome in last year
• Significant coronary atherosclerosis on angiography
• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

The study was terminated early due to difficulty in recruiting subjects, and ran short of funds. The sample size (n=2) was too small to perform a meaningful analysis.

Results Point of Contact

• Title: Dr. Yogish Kudva
• Organization: Mayo Clinic

kudva.yogish@mayo.edu

507-284-3964

Study Officials

• Yogish C. Kudva, M.B.B.S.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MBBS

Study Record Dates

• First Submitted: February 20, 2007
• First Posted: February 21, 2007
• Study Start: July 1, 2006
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: April 25, 2013
• Results First Posted: April 16, 2013

Record last verified: 2013-03

Locations

US (1)