Study of Islet Transplantation in Type 1 Diabetic Kidney Transplant Recipients

Islet Transplantation in Type 1 Diabetic Kidney Allograft Recipients

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

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type I
• Intervention / Treatment: Biological: Purified Pancreatic Islets; Drug: Etanercept

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Islet transplant; 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 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment.

Biological: Purified Pancreatic Islets; Islet after kidney transplant in patients with type I diabetes.; Drug: Etanercept; Given as induction for islet cell transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	1 year after the subject's first islet transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Decrease in HbA1c	Subjects will have a decrease in HbA1c of at least >1%	1 year after subject's first islet transplant
Stable or Decrease in Urinary Albumin and Creatinine Ratio and Serum Creatinine	Proteinuria and serum creatinine will be stable or decreased as compared to pre-transplant values	1 year after subjects initial islet transplant
An Absence Cardiovascular Events, Cerebral Vascular Accident, and Myocardial Infarction		1 year after the subject's first islet transplant
Impact on Vision	Improvement of frequency of interventions and from changes in reported visual acuity with optical refraction and severity of diabetic retinopathy	1 year after the subject's first islet transplant
Absence of Negative Renal Impact Measures	Loss of allograft survivial (return to dialysis, retransplant, death) and Renal allograft function meausred by SCr	1 year after the subject's first islet transplant
Improvement of Metabolic Control	Whether there is an improvement in metabolic control in IAK will be evaluated based on improvement in; basal c-peptide levels,; MMTT,; insulin requirements, and; c-peptide to glucose, creatinine ratio (CPGCR).	1 year after the subject's first islet transplant
Number of Participants With a Decrease of Severe Hypoglycemic Events	Subjects will have a decrease in severe hypoglycemic events	1 year after subject's first transplant
Reduction of Insulin Requriements	Evidence of partial success will be considered for subjects who have a reduction in insulin requirements but who are not insulin independent. This will be assessed by comparing the pre-transplant insulin requirement expressed as insulin units per kg per day with the requirement preceding subsequent islet transplants and the insulin requirements at 6 months and 1, 2, and 3 years after the first and last transplant.	1 year after the subject's first islet transplant

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Boston Area Diabetes Endocrinology Research Center (funded by NIDDK)
• Investigators: Principal Investigator: James F Markmann, MD, PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: April 23, 2009
• First Submitted That Met QC Criteria: April 24, 2009
• First Posted (Estimate): April 27, 2009

Study Record Updates

• Last Update Posted (Actual): November 29, 2017
• Last Update Submitted That Met QC Criteria: October 24, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Type I diabetes; Islet transplantation; Islet after Kidney Transplant
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept
• Other Study ID Numbers: IAK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO