Islet Cell Transplant for Type 1 Diabetes (TCD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by City of Hope Medical Center
Sponsor:
Collaborators:
University of California, Los Angeles
Benaroya Research Institute
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01909245
First received: July 22, 2013
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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) is an anti-rejection medication that works 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 is expected to protect islets and improve long-term transplant results. Transplant programs around the world have seen improved islet transplant results using T-cell depleting medications. Approximately 5-6 out of every 10 patients remain off insulin five years after transplant. These results are similar to those achieved with whole pancreas transplant without requiring major surgery, and therefore, may be an option for patients who are not eligible for a whole pancreas transplant.

The purpose of this study is to determine if islet cell transplantation using ATG, 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 Intervention Phase
Type 1 Diabetes Mellitus
Biological: Allogenic Human Islet Cells
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Islet Transplantation Using a T-Cell Depleting Immunosuppression Induction Regimen

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Proportion of subjects who are insulin independent, hypoglycemia free, AND with hemoglobin A1c ≤ 6.5% [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Reduction/Elimination of hypoglycemia [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Duration of insulin independence [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
  • Positive Stimulated C-peptide [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
  • Reduction in daily insulin requirement [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
  • Decline in insulin intake/100,000 IEQ infused [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
  • Insulin secretion during Intravenous Glucose Tolerance Test (IVGTT) and/or Mixed Meal Tolerance Test (MMTT) [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
  • Rate of alloimmune rejection [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
  • Rate of autoimmune reactivation [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
  • Incidence and severity of adverse events related to islet transplant procedure [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: Yes ]
  • Incidence and severity of adverse events related to immunosuppression [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: Yes ]
  • Incidence of change in immunosuppression drug regimen [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: Yes ]
  • Incidence of immune sensitization defined by presence of anti-HLA antibodies post-transplant that were absent pre-transplant [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: Yes ]
  • Incidence of discontinuation of immunosuppression [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: October 2013
Estimated Study Completion Date: July 2021
Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 68 Years
Genders Eligible for Study:   Both
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 hypoglycemia AND/OR hypoglycemia unawareness who have not received a previous transplant of any kind.
  • 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% -OR- T1D patients with a history of failed pancreas transplant > 6 months prior to screening.
  • 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
  3. Ability and willingness to comply with post-transplant regimen

    Additional Inclusion Criteria nITA Candidates Only

  4. Frequent hypoglycemia (blood glucose ≤ 54 mg/dl more than once per week) -OR- Hypoglycemia unawareness (Clarke score of 4 or more) -OR- One or more severe hypoglycemic episodes in 12 months preceding enrollment.

    Additional Inclusion Criteria for RT Candidates Only

  5. Failed pancreas transplant > 6 months prior to screening -OR- Two or fewer previous islet transplants > 1 month prior to screening with continuing exogenous insulin requirements and/or HbA1c > 6.5%

    Additional Inclusion Criteria for IAK Candidates Only

  6. Successful renal 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 renal graft in last 12 months and low risk of rejection
  9. Under continuing care of transplant nephrologist or surgeon

Exclusion Criteria:

  1. Body Mass Index (BMI) > 30
  2. Insulin requirements > 1.2 units/kg/day
  3. Known sensitization to both rATG -and- ATGAM
  4. Significant renal dysfunction
  5. Significant hepatobiliary disease
  6. Significant cardiovascular disease
  7. Hypertension despite appropriate treatment
  8. Hyperlipidemia despite appropriate treatment
  9. Anemia or other hematologic disorders that require medical treatment.
  10. WBC <3,000/ul
  11. Increased risk of bleeding, other chronic hemostasis disorders, or treatment with chronic anticoagulant therapy
  12. Recent unresolved acute infection (except for mild skin infection or nail fungal infection), or chronic infection
  13. Epstein-Barr Virus (EBV) IgG negative
  14. Any history of malignancy, except for completely resected squamous or basal cell carcinoma or in situ cancer of the cervix
  15. Recent history of non-compliance, or inability to demonstrate capacity to comply with strict blood glycemic control and insulin therapy
  16. Psychiatric illness that is untreated, or likely to interfere significantly with study compliance despite treatment
  17. Presence of preformed antibodies on panel reactive antibody screening > 25%
  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. Any medical condition that in the opinion of the investigator will interfere with safe participation in the trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01909245

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

Locations
United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Islet Cell Transplant Program    1-866-44-ISLET (1-866-444-7538    islets@coh.org   
Principal Investigator: Fouad Kandeel, MD, PhD         
Sponsors and Collaborators
City of Hope Medical Center
University of California, Los Angeles
Benaroya Research Institute
Investigators
Principal Investigator: Fouad Kandeel, MD, PhD City of Hope Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01909245     History of Changes
Other Study ID Numbers: 12446
Study First Received: July 22, 2013
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on July 23, 2014