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Study of Islet Transplantation in Type 1 Diabetic Kidney Transplant Recipients

Primary Purpose

Diabetes Mellitus, Type I

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Purified Pancreatic Islets
Etanercept
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type I focused on measuring Type I diabetes, Islet after Kidney Transplant, Islet transplantation

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Islet transplant

Arm 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 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of Participants With a Decrease in HbA1c
Subjects will have a decrease in HbA1c of at least >1%
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
An Absence Cardiovascular Events, Cerebral Vascular Accident, and Myocardial Infarction
Impact on Vision
Improvement of frequency of interventions and from changes in reported visual acuity with optical refraction and severity of diabetic retinopathy
Absence of Negative Renal Impact Measures
Loss of allograft survivial (return to dialysis, retransplant, death) and Renal allograft function meausred by SCr
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).
Number of Participants With a Decrease of Severe Hypoglycemic Events
Subjects will have a decrease in severe hypoglycemic events
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.

Full Information

First Posted
April 23, 2009
Last Updated
October 24, 2017
Sponsor
Massachusetts General Hospital
Collaborators
Boston Area Diabetes Endocrinology Research Center (funded by NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT00888628
Brief Title
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

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Boston Area Diabetes Endocrinology Research Center (funded by NIDDK)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type I
Keywords
Type I diabetes, Islet after Kidney Transplant, Islet transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Islet transplant
Arm Type
Experimental
Arm 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 2 doses of basiliximab. All patients will receive Etanercept to promote engraftment.
Intervention Type
Biological
Intervention Name(s)
Purified Pancreatic Islets
Intervention Description
Islet after kidney transplant in patients with type I diabetes.
Intervention Type
Drug
Intervention Name(s)
Etanercept
Intervention Description
Given as induction for islet cell transplant
Primary Outcome Measure Information:
Title
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.
Time Frame
1 year after the subject's first islet transplant
Secondary Outcome Measure Information:
Title
Number of Participants With a Decrease in HbA1c
Description
Subjects will have a decrease in HbA1c of at least >1%
Time Frame
1 year after subject's first islet transplant
Title
Stable or Decrease in Urinary Albumin and Creatinine Ratio and Serum Creatinine
Description
Proteinuria and serum creatinine will be stable or decreased as compared to pre-transplant values
Time Frame
1 year after subjects initial islet transplant
Title
An Absence Cardiovascular Events, Cerebral Vascular Accident, and Myocardial Infarction
Time Frame
1 year after the subject's first islet transplant
Title
Impact on Vision
Description
Improvement of frequency of interventions and from changes in reported visual acuity with optical refraction and severity of diabetic retinopathy
Time Frame
1 year after the subject's first islet transplant
Title
Absence of Negative Renal Impact Measures
Description
Loss of allograft survivial (return to dialysis, retransplant, death) and Renal allograft function meausred by SCr
Time Frame
1 year after the subject's first islet transplant
Title
Improvement of Metabolic Control
Description
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).
Time Frame
1 year after the subject's first islet transplant
Title
Number of Participants With a Decrease of Severe Hypoglycemic Events
Description
Subjects will have a decrease in severe hypoglycemic events
Time Frame
1 year after subject's first transplant
Title
Reduction of Insulin Requriements
Description
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.
Time Frame
1 year after the subject's first islet transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James F Markmann, MD, PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Study of Islet Transplantation in Type 1 Diabetic Kidney Transplant Recipients

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