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Allogeneic Islet Cells Transplanted Onto the Omentum

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ClinicalTrials.gov Identifier: NCT02213003
Recruitment Status : Active, not recruiting
First Posted : August 11, 2014
Last Update Posted : January 28, 2021
Sponsor:
Collaborators:
Juvenile Diabetes Research Foundation
Diabetes Research Institute Foundation
Information provided by (Responsible Party):
Rodolfo Alejandro, University of Miami

Tracking Information
First Submitted Date  ICMJE August 7, 2014
First Posted Date  ICMJE August 11, 2014
Last Update Posted Date January 28, 2021
Study Start Date  ICMJE September 2014
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 29, 2014)
  • A1c </= 6.5% and no severe hypoglycemia [ Time Frame: 1 year ]
    composite outcome
  • procedural complications [ Time Frame: 1 year ]
    safety
Original Primary Outcome Measures  ICMJE
 (submitted: August 7, 2014)
  • A1c </= 6.5% and no severe hypoglycemia [ Time Frame: 1 year ]
  • procedural complications [ Time Frame: 1 year ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allogeneic Islet Cells Transplanted Onto the Omentum
Official Title  ICMJE Allogeneic Islet Cells Transplanted Onto the Omentum
Brief Summary Current islet transplantation into the portal vein of the liver has shown the unique ability of islets to stabilize blood glucose levels and prevent severe hypoglycemia in a selected group of subjects with Type 1 diabetes. The main limitations of islet transplantation are the need for systemic immunosuppression to maintain function and the loss of islet function over time. Additionally, many studies have demonstrated that the current site of transplantation in the liver is not an ideal site due to several factors. These factors include (1) significant liver inflammation following islet infusion; (2) potential for life-threatening procedure-related complications such as bleeding and thrombosis; (3) high levels of immunosuppressive drugs and GI toxins in the liver contributing to islet toxicity; (4) the inability to retrieve islets after infusion; and (5) development of graft dysfunction in a number of recipients of intrahepatic allogeneic and autologous islets. The implantation of islets into the omentum will allow adequate engraftment of islets onto the omentum and will lead to comparable or superior functional and clinical outcomes than in the traditional intrahepatic site.
Detailed Description Islet transplantation will be performed in subjects with unstable Type 1 diabetes mellitus under permanent immunosuppression. Islets are re-suspended in autologous plasma and distributed on the omental surface by a minimal invasive approach. Cell adherence is achieved by addition of clinical-grade recombinant human thrombin that reacts with plasma to create a biocompatible, degradable gel containing the islet graft. The primary efficacy endpoint is the proportion of subjects with HbA1c ≤6.5% at 1 year AND free of severe hypoglycemic events from Day 28 to Day 365, inclusive, after the islet transplant. The primary safety endpoint is to demonstrate patient safety throughout all stages of the trial.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Type 1 Diabetes Mellitus
  • Hypoglycemia
  • Hypoglycemia Unawareness
Intervention  ICMJE Biological: Islet transplantation
Transplantation of at least 5000 islet equivalents/kg of body weight onto the Omentum.
Study Arms  ICMJE Experimental: Islet transplantation
Transplantation of at least 5000 islet equivalents/kg of body weight onto the omentum.
Intervention: Biological: Islet transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 7, 2014)
6
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2024
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male and female patients age 18 to 65 years of age.
  2. Ability to provide written informed consent.
  3. Mentally stable and able to comply with the procedures of the study protocol.
  4. Type1 diabetes with onset of disease at <40 years of age, insulin-dependence for > 5 years at the time of enrollment
  5. Absent stimulated c-peptide (<0.3ng/mL) in response to a mixed meal tolerance test.
  6. Involvement in intensive diabetes management
  7. At least one episode of severe hypoglycemia in the 12 months prior to study enrollment.
  8. Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more OR A Hypoglycemia score greater than or equal to the 90th percentile (1047) during the screening period; OR Marked glycemic lability and defined by a lability index score greater than or equal to the 90th percentile (433 mmol/L2/h•wk-1) during the screening period; OR A composite of a Clarke score of 3 or less and a hypoglycemia score greater than or equal to the 75th percentile (423) and a lability index greater than or equal to the 75th percentile (329) during the screening period.
  9. Subjects screening data from 20053135 protocol will be accepted for subjects eligible for this study. If 20053135 visit was 12 months prior to enrollment, Visit 2 laboratory should be repeated.

Exclusion Criteria:

  1. Body Mass Index (BMI) >30 kg/m2 or patient weight ≤50 kg.
  2. Insulin requirement of >1.0 IU/kg/day or <15 U/day.
  3. HbA1c >10%.
  4. Untreated proliferative diabetic retinopathy.
  5. Blood Pressure: SBP >160 mmHg or DBP >100 mmHg.
  6. Glomerular filtration rate <80 mL/min/1.73 m2 (calculated).
  7. Presence or history of macroalbuminuria (>300mg/g creatinine).
  8. Presence or history of panel-reactive anti-HLA antibodies.
  9. For female subjects: Serum or urine Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation. For male subjects: intent to procreate during the duration of the study or within 4 months after discontinuation or unwillingness to use effective measures of contraception. If sexually active, subject must use at least two medically accepted methods of birth control.
  10. Presence or history of active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB).
  11. Negative screen for Epstein-Barr Virus (EBV) by IgG determination.
  12. Invasive aspergillus, histoplasmosis, and coccidioidomycosis infection within one year prior to study enrollment.
  13. Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
  14. Active alcohol or substance abuse.
  15. Hb below the lower limits of normal at the local laboratory; lymphopenia (<1,000/µL), neutropenia (<1,500/µL), or thrombocytopenia (platelets <100,000/µL).
  16. A history of Factor V deficiency.
  17. Any coagulopathy or medical condition requiring long-term anticoagulant therapy.
  18. Severe co-existing cardiac disease,

    1. recent myocardial infarction (within past 6 months)
    2. evidence of ischemia on functional cardiac exam within the last year) left ventricular ejection fraction <30%.
  19. Persistent elevation of liver function tests at the time of study entry.
  20. Symptomatic cholecystolithiasis.
  21. Acute or chronic pancreatitis.
  22. Symptomatic peptic ulcer disease.
  23. Gastrointestinal disorders potentially interfering with the ability to absorb oral medications.
  24. Hyperlipidemia despite medical therapy (fasting LDL cholesterol > 130 mg/dL, fasting triglycerides > 200 mg/dl).
  25. Chronic use of systemic steroids, except for the use of ≤5 mg prednisone daily, or an equivalent dose of hydrocortisone, for physiological replacement only.
  26. Treatment with any anti-diabetic medications other than insulin within 4 weeks of enrollment.

23. Use of any investigational agents within 4 weeks of enrollment. 24. Administration of live attenuated vaccine(s) within 2 months of enrollment. 25. Any medical condition that, in the opinion of the investigator, will interfere with the safe participation in the trial.

26. Treatment with any immunosuppressive regimen at the time of enrollment. 27. A previous islet transplant. 28. A previous pancreas transplant 29. Inflammatory bowel disease. 30. History of intestinal obstructions. 31. Previous major abdominal surgery. 32. History of peritonitis.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02213003
Other Study ID Numbers  ICMJE 20140144
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: undecided. This is a small phase 1/2 pilot trial.
Responsible Party Rodolfo Alejandro, University of Miami
Study Sponsor  ICMJE Rodolfo Alejandro
Collaborators  ICMJE
  • Juvenile Diabetes Research Foundation
  • Diabetes Research Institute Foundation
Investigators  ICMJE
Principal Investigator: Rodolfo Alejandro University of Miami
PRS Account University of Miami
Verification Date January 2021

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