Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

Cadaveric Islet Transplantation in Patients With Insulin-Dependent Diabetes Mellitus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00579371
• Other study ID #: 0149-03-XX
• Secondary ID: BB IND 11397
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: March 17, 2004
• Est. completion date: March 2011

Study information

• Verified date: December 2023
• Source: University of Nebraska
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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

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, and transplanting the best combination of donor and recipient possible after HLA screening and final crossmatching.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 70 Years

Eligibility

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 panel reactive antibodies (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 a prothrombin time/international normalized ratio (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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Islets of Langerhans Transplantation

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	The Nebraska Medical Center	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
University of Nebraska

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Islet mass resulting in insulin independence/reduced exogenous insulin requirement	Insulin independence or reduced exogenous insulin required measured at one year post-transplantation.	1 year post-transplantation
Secondary	Graft survival	The survival of the Islets of Langerhans graft as measured at three years post-transplantation.	3 years post-transplantation
Secondary	Metabolic functional assessments of the islet graft	An assessment of the metabolic function of the islet of Langerhans graft as measured three years post-transplantation.	3 years post-transplantation