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Study of Islet Transplantation in Type 1 Diabetic Kidney Transplant Recipients

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ClinicalTrials.gov Identifier: NCT00888628
Recruitment Status : Completed
First Posted : April 27, 2009
Results First Posted : January 27, 2017
Last Update Posted : November 29, 2017
Sponsor:
Collaborator:
Boston Area Diabetes Endocrinology Research Center (funded by NIDDK)
Information provided by (Responsible Party):
James F. Markmann, MD, PhD, Massachusetts General Hospital

April 23, 2009
April 27, 2009
May 13, 2015
January 27, 2017
November 29, 2017
May 2009
August 2014   (Final data collection date for primary outcome 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. [ Time Frame: 1 year after the subject's first islet transplant ]
The safety of islets isolated at Massachusetts General Hospital (MGH) and the proportion of insulin independent subjects [ Time Frame: 1 year after the subject's first islet transplant ]
Complete list of historical versions of study NCT00888628 on ClinicalTrials.gov Archive Site
  • Number of Participants With a Decrease in HbA1c [ Time Frame: 1 year after subject's first islet transplant ]
    Subjects will have a decrease in HbA1c of at least >1%
  • Stable or Decrease in Urinary Albumin and Creatinine Ratio and Serum Creatinine [ Time Frame: 1 year after subjects initial islet transplant ]
    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 [ Time Frame: 1 year after the subject's first islet transplant ]
  • Impact on Vision [ Time Frame: 1 year after the subject's first islet transplant ]
    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 [ Time Frame: 1 year after the subject's first islet transplant ]
    Loss of allograft survivial (return to dialysis, retransplant, death) and Renal allograft function meausred by SCr
  • Improvement of Metabolic Control [ Time Frame: 1 year after the subject's first islet transplant ]

    Whether there is an improvement in metabolic control in IAK will be evaluated based on improvement in

    1. basal c-peptide levels,
    2. MMTT,
    3. insulin requirements, and
    4. c-peptide to glucose, creatinine ratio (CPGCR).
  • Number of Participants With a Decrease of Severe Hypoglycemic Events [ Time Frame: 1 year after subject's first transplant ]
    Subjects will have a decrease in severe hypoglycemic events
  • Reduction of Insulin Requriements [ Time Frame: 1 year after the subject's first islet transplant ]
    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.
  • HbA1c and Number of Hypoglycemic Events [ Time Frame: 1 year after subject's first islet transplant ]
  • Urinary Albumin and Creatinine Ratio and Serum Creatinine [ Time Frame: 1 year after subjects initial islet transplant ]
  • Cardiovascular events, CVA, and MI [ Time Frame: 1 year after the subject's first islet transplant ]
  • Impact on Vision [ Time Frame: 1 year after the subject's first islet tranplant ]
  • Renal Impact Measures Including Renal Allograft Survival [ Time Frame: 1 year after the subject's first islet transplant ]
  • Measures of Metabolic Control [ Time Frame: 1 year after the subject's first islet transplant ]
Not Provided
Not Provided
 
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

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.

Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Diabetes Mellitus, Type I
  • Biological: Purified Pancreatic Islets
    Islet after kidney transplant in patients with type I diabetes.
  • Drug: Etanercept
    Given as induction for islet cell transplant
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.

Interventions:
  • Biological: Purified Pancreatic Islets
  • Drug: Etanercept
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
7
8
August 2016
August 2014   (Final data collection date for primary outcome measure)

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.

Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00888628
IAK
Yes
Not Provided
Plan to Share IPD: No
James F. Markmann, MD, PhD, Massachusetts General Hospital
Massachusetts General Hospital
Boston Area Diabetes Endocrinology Research Center (funded by NIDDK)
Principal Investigator: James F Markmann, MD, PhD Massachusetts General Hospital
Massachusetts General Hospital
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP