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Islet Allotransplantation in Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT01705899
Recruitment Status : Enrolling by invitation
First Posted : October 12, 2012
Last Update Posted : March 20, 2019
Sponsor:
Information provided by (Responsible Party):
Amer Rajab, Ohio State University

Brief Summary:

Islet transplantation can provide physiologic insulin replacement to patients with type 1 diabetes without the complications associated with whole pancreas transplantation. The purpose of this study is to achieve insulin-independence in patients with type 1 diabetes, thereby eliminating the need for exogenous insulin injections to maintain normal glucose levels, ameliorating severe hypoglycemia and potentially decreasing the development of diabetes-related complications. This study will investigate islet transplantation in subjects who have preserved renal function and subjects who have undergone cadaveric renal transplantation, since the latter subjects are already on immunosuppression.

This is a single center, prospective trial of islet transplantation in subjects receiving islets alone or islets after kidney transplant. This is a phase I study investigating the use of islet transplantation for the treatment of type 1 diabetes. Subjects will be eligible for an islet transplant if they meet all of the inclusion criteria and none of the exclusion criteria outlined in the protocol. In brief, the aims of this study are to establish an islet transplant program at the Ohio State University, determine the safety of islet transplantation in islet alone and kidney transplant recipients, determine whether islet transplantation will reduce the frequency of severe hypoglycemic events, determine whether a novel steroid-free immunosuppressive protocol will prevent rejection in islet transplants and to achieve insulin independence at one year after the final islet transplant.


Condition or disease Intervention/treatment Phase
Type 1 Diabetes Drug: Human Pancreatic Islets Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Islet Allotransplantation in Type 1 Diabetes
Study Start Date : November 2006
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : October 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: Subjects with preserved kidney function
Subjects with preserved renal function that have not previously received a kidney transplant will be treated with Human Pancreatic Islets (in the form of islets alone - IA).
Drug: Human Pancreatic Islets
Pancreatic islet tissue suspended in 150 - 300 ml of phenol red-free CMRL-1066 Transplant Media supplemented with 4% (w/v) HSA and 16mM HEPES in a 600ml transfer pack. Heparin will be administered at 70 IU/kg recipient body weight. Administered by intra-portal vein infusion. To be administered once, however, if full graft function is not achieved, a second or third dose of Pancreatic Islets may be given within 18 months of the first transplant.

Experimental: Subjects with prior kidney transplant
Subjects with renal failure secondary to diabetes who have received a prior kidney transplant at least 6 months previously and have stable renal function on a steroid-free immunosuppressive regimen will receive Human Pancreatic Islets (in the form of islets after kidney - IAK).
Drug: Human Pancreatic Islets
Pancreatic islet tissue suspended in 150 - 300 ml of phenol red-free CMRL-1066 Transplant Media supplemented with 4% (w/v) HSA and 16mM HEPES in a 600ml transfer pack. Heparin will be administered at 70 IU/kg recipient body weight. Administered by intra-portal vein infusion. To be administered once, however, if full graft function is not achieved, a second or third dose of Pancreatic Islets may be given within 18 months of the first transplant.




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant ]
  2. Incidence of serious adverse events [ Time Frame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant ]

    Serious adverse events will be defined (in accordance with FDA Title 21 CFR 312.32) as the following:

    • Death
    • Life-threatening and placing the subject at immediate risk of death
    • Hospitalization
    • Persistent or significant disability or incapacity
    • Congenital abnormal/birth defects
    • Requiring medical or surgical intervention to prevent permanent damage

  3. Incidence of infectious complications [ Time Frame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant ]
  4. Incidence of procedural-related events [ Time Frame: Day 1 post-transplant ]
    Ex. Bleeding or portal vein thrombosis

  5. Incidence of elevated liver function tests [ Time Frame: Day 1 post-transplant ]
  6. Incidence of hypoglycemia [ Time Frame: Day 1 post-transplant ]
  7. Incidence of procedural-related events [ Time Frame: Day 2 post-transplant ]
    Ex. Bleeding or portal vein thrombosis

  8. Incidence of elevated liver function tests [ Time Frame: Day 2 post-transplant ]
  9. Incidence of hypoglycemia [ Time Frame: Day 2 post-transplant ]
  10. Incidence of procedural-related events [ Time Frame: Day 3 post-transplant ]
    Ex. Bleeding or portal vein thrombosis

  11. Incidence of elevated liver function tests [ Time Frame: Day 3 post-transplant ]
  12. Incidence of hypoglycemia [ Time Frame: Day 3 post-transplant ]
  13. Incidence of elevated liver function tests [ Time Frame: Day 5 post-transplant ]
  14. Incidence of hypoglycemia [ Time Frame: Day 5 post-transplant ]
  15. Incidence of elevated liver function tests [ Time Frame: Day 7 post-transplant ]
  16. Incidence of hypoglycemia [ Time Frame: Day 7 post-transplant ]
  17. Incidence of elevated liver function tests [ Time Frame: Day 10 post-transplant ]
  18. Incidence of hypoglycemia [ Time Frame: Day 10 post-transplant ]
  19. Incidence of elevated liver function tests [ Time Frame: Day 14 post-transplant ]
  20. Incidence of hypoglycemia [ Time Frame: Day 14 post-transplant ]
  21. Incidence of elevated liver function tests [ Time Frame: Day 21 post-transplant ]
  22. Incidence of hypoglycemia [ Time Frame: Day 21 post-transplant ]
  23. Incidence of abnormalities in lipids [ Time Frame: Day 28 post-transplant ]
  24. Incidence of elevated liver function tests [ Time Frame: Day 28 post-transplant ]
  25. Incidence of donor-specific antibody development [ Time Frame: Day 28 post-transplant ]
  26. Incidence of hypoglycemia [ Time Frame: Day 28 post-transplant ]
  27. Incidence of elevated liver function tests [ Time Frame: Day 42 post-transplant ]
  28. Incidence of hypoglycemia [ Time Frame: Day 42 post-transplant ]
  29. Incidence of elevated liver function tests [ Time Frame: Day 56 post-transplant ]
  30. Incidence of hypoglycemia [ Time Frame: Day 56 post-transplant ]
  31. Incidence of elevated liver function tests [ Time Frame: Day 90 post-transplant ]
  32. Incidence of hypoglycemia [ Time Frame: Day 90 post-transplant ]
  33. Incidence of abnormalities in lipids [ Time Frame: Day 90 post-transplant ]
  34. Incidence of donor-specific antibody development [ Time Frame: Day 90 post-transplant ]
  35. Incidence of elevated liver function tests [ Time Frame: Day 120 post-transplant ]
  36. Incidence of hypoglycemia [ Time Frame: Day 120 post-transplant ]
  37. Incidence of elevated liver function tests [ Time Frame: Day 180 post-transplant ]
  38. Incidence of hypoglycemia [ Time Frame: Day 180 post-transplant ]
  39. Incidence of abnormalities in lipids [ Time Frame: Day 180 post-transplant ]
  40. Incidence of donor-specific antibody development [ Time Frame: Day 180 post-transplant ]
  41. Incidence of elevated liver function tests [ Time Frame: Day 270 post-transplant ]
  42. Incidence of hypoglycemia [ Time Frame: Day 270 post-transplant ]
  43. Incidence of abnormalities in lipids [ Time Frame: Day 270 post-transplant ]
  44. Incidence of donor-specific antibody development [ Time Frame: Day 270 post-transplant ]
  45. Incidence of elevated liver function tests [ Time Frame: Day 365 post-transplant ]
  46. Incidence of abnormalities in lipids [ Time Frame: Day 365 post-transplant ]
  47. Incidence of hypoglycemia [ Time Frame: Day 365 post-transplant ]
  48. Incidence of donor-specific antibody development [ Time Frame: Day 365 post-transplant ]
  49. Change in microalbumin level [ Time Frame: Days 180 and 365 post-transplant ]
  50. Change in measured creatinine clearance [ Time Frame: Days 180 and 365 post-transplant ]

Secondary Outcome Measures :
  1. Amount of daily insulin units required [ Time Frame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant ]
  2. Measurement of C-peptide [ Time Frame: Days 1, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant ]
  3. Change in c-peptide level from fasting following administration of mixed meal [ Time Frame: Days 180 and 365 post-transplant ]
    Patients fasting c-peptide will be measured, then patient will be given a mixed meal of Ensure. The c-peptide level will be checked again at 90 minutes after administration of mixed meal.

  4. Change in acute insulin response to glucose [ Time Frame: Days 180 and 365 post-transplant ]
    As determined by oral glucose tolerance test and/or intravenous glucose tolerance test

  5. Incidence of blood glucose level <140mg/dl two hours after oral glucose tolerance tests [ Time Frame: Days 180 and 365 post-transplant ]
  6. Change in Quality of Life [ Time Frame: Days 180 and 365 post-transplant ]
  7. Change in hypoglycemia score [ Time Frame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant ]
  8. Change in glycemic lability score [ Time Frame: Days 1, 2, 3, 5, 7, 10, 14, 21, 28, 42, 56, 90, 120, 180, 270 and 365 days post-transplant ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Type 1 diabetes > 5 years
  2. First islet transplant
  3. Demonstrate intensive efforts to manage diabetes for last 6 months (≥4 SMBG/day, ≥3 injections of insulin/day or use of pump and ≥3 contacts with diabetes care team in last 12 months)
  4. Metabolic complications: at least one of the following:

    •Reduced hypoglycemia awareness (inability to sense hypoglycemia until blood glucose falls to < 54 mg/dl or > one hypoglycemic episode in last 12 months requiring outside help and not explained by clear precipitant)

    •≥2 severe hypoglycemic events or ≥2 hospitalizations for diabetic ketoacidosis (DKA) in last year.

  5. Ability to provide written informed consent
  6. Age 18-65
  7. Specific for group 2: All of above (1-6) with renal transplant at least 6 months previous

Exclusion Criteria:

  1. Age < 18 years or > 65 years
  2. Inability to provide informed consent
  3. Body Mass Index > 29 kg/m2
  4. Insulin requirement of > 50 units/day
  5. Stimulated C-peptide ≥ 0.2 ng/ml
  6. Current panel reactive anti-HLA antibodies >20%
  7. Cardiovascular instability
  8. Previous islet transplant
  9. History of malignancy except squamous and basal cell skin cancer unless disease-free for > 2 years determined by independent oncologist
  10. Active peptic ulcer disease
  11. Condition that may interfere with absorption of medications
  12. Hemoglobin A1C > 12%
  13. Invasive aspergillus infection within one year
  14. Varicella titer index <1.0
  15. Rubella titer <10 IU/ml
  16. Psychiatric disorder
  17. Untreated hyperlipidemia: fasting total cholesterol >240 mg/dl, low density lipoprotein>130 mg/dl, or triglycerides >200 mg/dl
  18. Hemoglobin <10 g/dl for females, and <11 g/dl for males, white blood cell count < 3,000/µL, platelet count of <150,000/microliter, CD4+ count <500/microliter
  19. Liver function test abnormalities (if any value > 1.5 times normal, candidate will be excluded. If 1-1.5 times normal, test will be repeated. If re-test value remains above normal, candidate will be excluded).
  20. Prostate specific antigen >4.0 ng/ml
  21. Presence of gallstones, liver hemangioma, cirrhosis or evidence of portal hypertension
  22. Untreated proliferative diabetic retinopathy
  23. Females: positive pregnancy test, intent for future pregnancy, or any subject of reproductive age who is not surgically sterile and is unable or unwilling to use acceptable method of contraception
  24. Female subjects who are breast-feeding
  25. Adrenal insufficiency: 8am cortisol >19 mcg/dl adequate. Values 19 mcg/dl will be followed by Adreno-Corticotropic Hormone stimulation test
  26. Any disease or condition that requires use of chronic steroids
  27. Coagulopathy or use of chronic anticoagulation
  28. Hyperthyroidism unless treated with radioactive iodine or surgery
  29. Thyroid function tests outside normal range
  30. Active alcoholism or other substance abuse within the past six months
  31. History of non-adherence. Questionable adherence requires agreement entered and compliance demonstrated for at least 3 months
  32. Active infection including hepatitis B or C, human immunodeficiency virus positive, positive Mantoux test [unless previously immunized with Bacillus Calmette-Guerin], or X-ray evidence of pulmonary infection
  33. Inability to reach hospital within 6 hours of notification
  34. Failure to clear psychological or psychiatric screen
  35. Medical condition or circumstance that investigator finds will interfere with safe completion of the study

Exclusion criteria specific for group 1:

  1. Receipt of previous transplant (excluding pancreas)
  2. Creatinine clearance <50 ml/minute for females and <60 ml/minute for males or macroalbuminuria (>500 mg/24h)

Exclusion criteria specific for group 2:

  1. Creatinine clearance <40ml/minute
  2. Renal transplant in last 6 months
  3. Current use of corticosteroids

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01705899


Locations
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United States, Ohio
The Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University
Investigators
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Principal Investigator: Amer Rajab, MD, PhD Ohio State University

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Responsible Party: Amer Rajab, Associate Professor of Surgery; Director of Pancreas and Islet Transplantation, Ohio State University
ClinicalTrials.gov Identifier: NCT01705899     History of Changes
Other Study ID Numbers: IRB 2006H0200
First Posted: October 12, 2012    Key Record Dates
Last Update Posted: March 20, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual participant data for patients who agree is entered into a multi-center islet transplant data registry (no personally identifiable information will be shared). Upon completion of the study, results may also be published in a peer-reviewed journal.

Keywords provided by Amer Rajab, Ohio State University:
Type 1 Diabetes
Islet transplant
Kidney transplant

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases