Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus
This study is enrolling participants by invitation only.
Sponsor:
University of Nebraska
Information provided by:
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00579371
First received: December 17, 2007
Last updated: June 25, 2010
Last verified: June 2010
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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 HLA screening and final crossmatching
| Condition | Intervention | Phase |
|---|---|---|
|
Islets of Langerhans Transplantation Diabetes Mellitus, Type 1 |
Other: Islets of Langerhans |
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: | Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus |
Resource links provided by NLM:
Further study details as provided by University of Nebraska:
Primary Outcome Measures:
- Incidence of insulin independence with a single islet transplant [ Time Frame: 1 year post-transplantation ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Islet mass resulting in insulin independence/reduced exogenous insulin requirement [ Time Frame: 1 year post-transplantation ] [ Designated as safety issue: No ]
- Graft survival [ Time Frame: 3 years post-transplantation ] [ Designated as safety issue: No ]
- Metabolic functional assessments of the islet graft [ Time Frame: 3 years post-transplantation ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 10 |
| Study Start Date: | January 2008 |
| Estimated Study Completion Date: | January 2013 |
| Estimated Primary Completion Date: | January 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: 1 |
Other: Islets of Langerhans
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.
|
Eligibility| Ages Eligible for Study: | 19 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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
Exclusion Criteria:
- 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
- Positive pregnancy test, intention of future pregnancy, or presently breast-feeding
- Evidence of sensitization on PRA
- Insulin requirement >0.7 IU/kg/day or HbA1c >15%
- Hyperlipidemia
- Under treatment for a medical condition requiring chronic use of steroids
- Use of Coumadin or other anticoagulant therapy (except aspirin) or PT-INR>1.5
- Diagnosis of Addison's disease
Additional Exclusion Criteria for Group 2 Subjects:
- Any history of organ transplantation other than kidney or pancreas
- Any previous graft lost to rejection
- Any history of early, multiple, or vascular renal allograft rejection
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00579371
Locations
| United States, Nebraska | |
| The Nebraska Medical Center | |
| Omaha, Nebraska, United States, 68198 | |
Sponsors and Collaborators
University of Nebraska
Investigators
| Principal Investigator: | R Brian Stevens, MD PhD | University of Nebraska |
More Information
No publications provided
| Responsible Party: | R Brian Stevens, MD, PhD, University of Nebraska Medical Center |
| ClinicalTrials.gov Identifier: | NCT00579371 History of Changes |
| Other Study ID Numbers: | 149-03-FB, BB IND 11397 |
| Study First Received: | December 17, 2007 |
| Last Updated: | June 25, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by University of Nebraska:
|
islet transplantation type 1 diabetes mellitus steroid-free immunosuppression rabbit anti-thymocyte globulin |
Additional relevant MeSH terms:
|
Diabetes Mellitus Diabetes Mellitus, Type 1 Glucose Metabolism Disorders Metabolic Diseases |
Endocrine System Diseases Autoimmune Diseases Immune System Diseases |
ClinicalTrials.gov processed this record on May 23, 2013