Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus

NCT00579371 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 0149-03-XXBB IND 11397
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

We hypothesize that the following improvements to islet transplantation will increase the islet mass successfully isolated and allow for engraftment from a single pancreas. The improvements are:

• Using Two-Layer method preservation to improve pancreas quality before islet isolation
• Maintaining isolated islets in culture before transplantation
• Using a steroid-free immunosuppression regimen
• Transplanting the best combination of donor and recipient possible after human leukocyte antigens (HLA) screening and final crossmatching

Conditions

Islets of Langerhans Transplantation; Diabetes Mellitus, Type 1

Keywords

islet transplantation; type 1 diabetes mellitus; steroid-free immunosuppression; rabbit anti-thymocyte globulin

Outcome Measures

Primary Outcomes (1)

• Incidence of insulin independence with a single islet transplant

  Incidence of insulin independence with a single transplantation measured at one year post-transplantation.

  1 year post-transplantation

Secondary Outcomes (3)

• Islet mass resulting in insulin independence/reduced exogenous insulin requirement

  1 year post-transplantation

• Graft survival

  3 years post-transplantation

• Metabolic functional assessments of the islet graft

  3 years post-transplantation

Study Arms (1)

Transplantation of Islets of Langerhans

EXPERIMENTAL

Subjects will receive islets isolated from one donor pancreas per transplantation event. Subjects will receive a cumulative dose of 8,000 International Units/kg. Islets will be infused intraportally. If necessary, additional transplantation events will be performed.

Drug: Islets of Langerhans

Interventions

Islets of Langerhans DRUG

Subjects will receive islets isolated from one donor pancreas per transplantation event. Subjects will receive a cumulative dose of 8,000IE/kg. Islets will be infused intraportally. If necessary, additional transplantation events will be performed.

Also known as: transplanted islets of Langerhans

Transplantation of Islets of Langerhans

Eligibility Criteria

• Age: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Group 1: Diagnosis of Type-1 diabetes mellitus for more than 5 years with at least one of the following complications:
• Metabolic lability/instability (two or more episodes of severe hypoglycemia) or two or more hospital visits for diabetic ketoacidosis during the previous year
• Progression of secondary complications of diabetes as determined by The Nebraska Medical Center/University of Nebraska Medical Center staff endocrinologists
• Group 2: Diagnosis of Type-1 diabetes with successful renal transplant on steroid-free, FK506/rapamycin-based immunosuppression

You may not qualify if:

• Severe co-existing cardiac disease
• Active alcohol or substance abuse, including cigarette smoking
• Psychiatric disorder making the subject not a suitable candidate for transplantation
• History of medical non-compliance
• Active infection, including hepatitis C and B, HIV, and tuberculosis (or suspected tuberculosis)
• Any history of malignancy except squamous or basal cell skin cancer
• BMI \>28 kg/meter-squared, or body weight \>80kg at screening visit, or \>85kg on the day of transplantation (due to the difficulty of obtaining a sufficiently large islet mass to adequately treat either large patients or those whose obesity elevates their insulin needs)
• Positive C-peptide response to intravenous glucose tolerance test and Mixed Meal glucose tolerance test: any C-peptide \>0.3 ng/mL post infusion
• Inability to provide informed consent
• Age less than 19 or greater than 70 years
• Creatinine clearance \<60 mL/min/1.73 meter-squared for Group 1 and creatinine clearance \<40 mL/min/1.73 meter-squared for Group 2 (those subjects currently on immunosuppression due to previous kidney transplant)
• Macroalbuminuria (urinary albumin excretion rate \>300 mg/24h) for Group 1 and macroalbuminuria (urinary albumin excretion rate \>600mg/24h) for Group 2
• Baseline Hb \<10 gm/dL
• Baseline liver function tests outside of normal range
• Presence of gallstones or hemangioma in liver on baseline ultrasound exam

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

The Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Islets of Langerhans Transplantation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Endocrine Surgical Procedures; Surgical Procedures, Operative; Transplantation

Study Officials

• R Brian Stevens, MD PhD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2007
• First Posted: December 24, 2007
• Study Start: March 17, 2004
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: December 21, 2023

Record last verified: 2023-12

Locations

US (1)