Clinical trial NCT00888628: Study of Islet Transplantation in Type 1 Diabetic Kidney Transplant Recipients
Official title: Islet Transplantation in Type 1 Diabetic Kidney Allograft Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diabetes Mellitus, Type I
Keywords: Type I diabetes
Islet after Kidney Transplant
Islet transplantation
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Boston Area Diabetes Endocrinology Research Center (funded by NIDDK)
First posted: 2009-04-27
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to learn if islet transplantation is an effective treatment for Type 1 diabetes in people who have had a kidney transplant.

The primary objectives of the study are:

- To set up islet transplantation in patients who have had a kidney transplant and who are using an immunosuppressive regimen that works

The Secondary objective of the study is:

* To find out if successful islet transplantation leads to improved metabolic control and reduced renal complication from diabetes

Detailed description: Patients will receive (an) infusion(s) of in vitro cultured islets with the goal of achieving insulin independence. For the first islet transplant, patients will receive induction therapy with rabbit anti-thymocyte globulin (ATG, 5 doses) and will remain on their maintenance immunosuppression regimen already in place for their renal allograft. Induction therapy for subsequent transplants will be 2doses of basiliximab.

All patients will receive Etanercept to promote engraftment.

Eligibility criteria: Inclusion Criteria:

* Male and female subjects
* Age 18 to 70 years of age
* Have insulin dependent Diabetes Mellitus Type 1
* Are post-renal transplant on maintenance immunosuppression with stable renal function
* HbA1c \> 7.5% or \< 7.5% and hypoglycemia unawareness

Exclusion Criteria:

* Weight more than 90 kg
* Insulin requirement \> 60 Units/day
* Other (non-kidney) organ transplants except prior failed pancreatic graft.
* Untreated or unstable proliferative diabetic retinopathy
* Presence of de novo antibody production since the renal allograft or either Class I or Class II panel-reactive anti-HLA antibodies
* Active infection
* Negative screen for Epstein-Barr virus (EBV)
* Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin
* History of Factor V Leiden mutation
* Any coagulopathy or medical condition requiring long-term anticoagulant therapy (e.g. warfarin) after transplantation (low-dose aspirin treatment is allowed) or subjects with international normalized ratio (INR) \> 1.5
* Severe co-existing cardiac disease
* Persistent elevation of liver function tests at the time of study entry
* Acute or chronic pancreatitis
* Male subjects with elevation of prostate specific antigen
* Pregnancy
* Positive screen for polyoma (BK) virus
* Untreated hyperlipidemia
* Recent hemorrhagic stroke
* Factors associated with an increased risk of bleeding

Contact PI for complete Incl-Excl criteria list.

Primary outcomes:
measure: Insulin Independence With Both an HbA1c ≤ 6.5% and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant or a Reduction in HbA1c of at Least 1 Point and no Severe Hypoglycemic Events at 1 Year After the First Islet Transplant.
timeFrame: 1 year after the subject's first islet transplant
Secondary outcomes:
measure: Number of Participants With a Decrease in HbA1c
timeFrame: 1 year after subject's first islet transplant
measure: Stable or Decrease in Urinary Albumin and Creatinine Ratio and Serum Creatinine
timeFrame: 1 year after subjects initial islet transplant
measure: An Absence Cardiovascular Events, Cerebral Vascular Accident, and Myocardial Infarction
timeFrame: 1 year after the subject's first islet transplant
measure: Impact on Vision
timeFrame: 1 year after the subject's first islet transplant
measure: Absence of Negative Renal Impact Measures
timeFrame: 1 year after the subject's first islet transplant
measure: Improvement of Metabolic Control
timeFrame: 1 year after the subject's first islet transplant
measure: Number of Participants With a Decrease of Severe Hypoglycemic Events
timeFrame: 1 year after subject's first transplant
measure: Reduction of Insulin Requriements
timeFrame: 1 year after the subject's first islet transplant
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: James F Markmann, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: