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Islet Cell Transplant for Type 1 Diabetes (TCD)

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ClinicalTrials.gov Identifier: NCT01909245
Recruitment Status : Recruiting
First Posted : July 26, 2013
Last Update Posted : January 30, 2019
Sponsor:
Collaborator:
University of California, Los Angeles
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:

City of Hope National Medical Center, located in Duarte, CA, is hosting a clinical study on islet cell transplantation, an experimental procedure being evaluated as a treatment for patients with type 1 diabetes. Islet cell transplantation involves taking insulin-producing cells from organ donors and transplanting them into the liver of a patient with diabetes. Once transplanted, the islets produce insulin, which can improve blood sugar control and eliminate the need to inject insulin or use an insulin pump.

Anti-thymocyte globulin (ATG) and alemtuzumab (Campath) are anti-rejection medications that work by decreasing a patient's T-cells. T-cells are special white blood cells that recognize and destroy unwanted things like infections but can also attack transplanted cells and organs. Reducing the number of T-cells at the time of transplant may protect islets and improve long-term transplant success. In previous research studies, islet transplantation has been successful in reducing low blood sugar episodes, improving overall blood sugar control, and in some cases, allowing patients with type 1 diabetes to stop taking insulin.

The purpose of this study is to determine if islet cell transplantation using ATG or alemtuzumab, along with additional medications to prevent the body from rejecting the transplanted cells, is a safe and effective treatment for type 1 diabetes. Study participants may receive up to three islet transplants and will be followed for five years to monitor blood sugar control, islet transplant function, and changes in quality of life.


Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Biological: Allogenic Human Islet Cells Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Islet Transplantation Using a T-Cell Depleting Immunosuppression Induction Regimen
Study Start Date : October 2013
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021


Arm Intervention/treatment
Experimental: Single Arm Study Biological: Allogenic Human Islet Cells
Intraportal (into the liver) infusion of islet cells, with a maximum of three islet transplants.
Other Name: Islet transplant, islet transplantation




Primary Outcome Measures :
  1. Proportion of subjects who are insulin independent, hypoglycemia free, AND with hemoglobin A1c < 6.5% at 1 year post-transplant [ Time Frame: 1 year post-transplant ]
  2. Proportion of subjects who are insulin independent, hypoglycemia free, AND with hemoglobin A1c < 6.5% at 2 years post-transplant [ Time Frame: 2 years post-transplant ]
  3. Proportion of subjects who are insulin independent, hypoglycemia free, AND with hemoglobin A1c < 6.5% at 5 years post-transplant [ Time Frame: 5 years post-transplant ]

Secondary Outcome Measures :
  1. Proportion of subjects who are free of severe hypoglycemic episodes AND have a hemoglobin A1c < 7.0% [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]

Other Outcome Measures:
  1. Proportion of subjects experiencing reduction/elimination of hypoglycemic episodes [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]
  2. Duration of insulin independence [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]
  3. Proportion of subjects who maintain a positive c-peptide secretion response to glucose/glucagon stimulation [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]
  4. Change in average daily insulin use compared to baseline [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]
  5. Decline in insulin intake/100,000 IEQ infused [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]
  6. Insulin secretion during Intravenous Glucose Tolerance Test (IVGTT) and/or Mixed Meal Tolerance Test (MMTT) [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]
  7. Rate of alloimmune rejection [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]
  8. Rate of autoimmune reactivation [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]
  9. Incidence and severity of adverse events related to islet transplant procedure [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]
  10. Incidence and severity of adverse events related to immunosuppression [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]
  11. Incidence of change in immunosuppression drug regimen [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]
  12. Incidence of immune sensitization defined by presence of anti-HLA antibodies post-transplant that were absent pre-transplant [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]
  13. Incidence of discontinuation of immunosuppression [ Time Frame: +75 days, +6 months, +12 months, and +2, +3, +4 and +5 years post islet transplant ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 68 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Three different categories of patients with Type 1 Diabetes will be considered for study participation:

  • Naïve islet transplant alone (nITA) candidates: T1D patients complicated by frequent/severe hypoglycemia, hypoglycemia unawareness, AND/OR otherwise unstable blood glucose control who have not received a previous transplant (except for a failed pancreas more than 6 months prior to screening)
  • Repeat transplant (RT) candidates: T1D patients who have received two or fewer previous islet transplants > 1 month prior to screening, but continue to require exogenous insulin treatment or have an HbA1c > 6.5%
  • Islet after kidney transplant (IAK) candidates: T1D patients with a history of successful renal transplant > 3 months prior to screening

Inclusion criteria for all candidates:

  1. Age 18-68 years
  2. Type 1 diabetes mellitus for at least 5 years
  3. Ability and willingness to comply with post-transplant regimen, including taking anti-rejection medications, use of reliable contraception, frequent clinic visits, lab tests, careful recording of blood glucose values, insulin doses and medications, and completing detailed follow-up studies

    Additional Inclusion Criteria nITA Candidates Only

  4. Unstable blood sugar control characterized by:

    Frequent hypoglycemia (blood glucose ≤ 54 mg/dl more than once per week) -AND/OR- Hypoglycemia unawareness (Clarke score of 4 or more) -AND/OR- One or more severe hypoglycemic episodes in 12 months preceding enrollment. -AND/OR- Erratic blood glucose levels that interfere with daily activities -AND/OR- One or more hospital visits for diabetic ketoacidosis in the 12 months preceding enrollment

    Additional Inclusion Criteria for RT Candidates Only

  5. One or two or previous islet transplants > 1 month prior to screening with continuing insulin requirements and/or HbA1c > 6.5%

    Additional Inclusion Criteria for IAK Candidates Only

  6. Successful kidney transplant > 3 months prior to screening
  7. Stable maintenance immunosuppression consisting of tacrolimus alone or in conjunction with sirolimus, mycophenolate mofetil, myfortic or azathoprine; or cyclosporine in conjunction with sirolimus, mycophenolate mofetil, or myfortic +/- ≤ 10 mg/day corticosteroids
  8. No history of acute rejection related to kidney graft in last 12 months and low risk of rejection
  9. Under continuing care of physician for kidney graft, who has provided letter in support of candidate's consideration for study participation

Exclusion Criteria:

  1. Body Mass Index (BMI) > 33
  2. Insulin requirements > 1.2 units/kg/day
  3. Known sensitization to both rATG -and- alemtuzumab
  4. Significant kidney dysfunction
  5. Significant liver/gall bladder disease
  6. Significant cardiovascular disease
  7. Active proliferative retinopathy
  8. High blood pressure despite appropriate treatment
  9. High cholesterol/triglycerides despite appropriate treatment
  10. Anemia or other blood disorders that require medical treatment
  11. WBC <3,000/ul
  12. Increased risk of bleeding, other chronic hemostasis disorders, or treatment with chronic anticoagulant therapy
  13. Recent unresolved acute infection (except for mild skin infection or nail fungal infection), or chronic infection
  14. Epstein-Barr Virus (EBV) IgG negative
  15. Any history of malignancy, except for completely resected squamous or basal cell carcinoma of the skin or in situ cancer of the cervix
  16. Recent history of non-adherence to medical treatment, or inability to demonstrate capacity to comply with strict blood glycemic control and insulin therapy
  17. Psychiatric illness that is untreated, or likely to interfere significantly with study compliance despite treatment
  18. Previous organ/tissue transplant, except as noted above
  19. Administration of live attenuated vaccines within 2 months of enrollment
  20. Presence of a chronic disease that must be chronically treated with a contraindicated agent
  21. Use of investigational agents within four weeks of enrollment
  22. Active alcohol or substance abuse, including cigarette smoking
  23. Pregnant women, women intending future pregnancy, women of reproductive potential who are unable or unwilling to follow effective contraceptive measures prior to study entry and for as long as they are on immunosuppression medication, and women presently breast feeding are excluded
  24. Individuals without health insurance
  25. History of gastric bypass
  26. Any medical condition that in the opinion of the investigator will interfere with safe participation in the trial

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): NCT01909245


Contacts
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Contact: Islet Cell Transplant Program 1-866-44-ISLET (1-866-444-7538 islets@coh.org

Locations
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United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Islet Cell Transplant Program    866-444-7538    islets@coh.org   
Principal Investigator: Fouad Kandeel, MD, PhD         
Sponsors and Collaborators
City of Hope Medical Center
University of California, Los Angeles
Investigators
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Principal Investigator: Fouad Kandeel, MD, PhD City of Hope Medical Center

Additional Information:
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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01909245     History of Changes
Other Study ID Numbers: 12446
First Posted: July 26, 2013    Key Record Dates
Last Update Posted: January 30, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by City of Hope Medical Center:
Islet cells
hypoglycemia
hypoglycemia unawareness
islet after kidney transplantation
islet transplant
insulin independence
insulin dependence
labile diabetes

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