Allogeneic Islet Cells Transplanted Onto the Omentum
| Status: | Recruiting |
|---|---|
| Conditions: | Endocrine, Diabetes, Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 12/13/2018 |
| Start Date: | September 2014 |
| End Date: | May 2022 |
| Contact: | Rodolfo Alejandro, MD |
| Email: | ralejand@med.miami.edu |
| Phone: | 3052435324 |
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.
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.
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.
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.
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.
We found this trial at
1
site
Miami, Florida 33136
Principal Investigator: Rodolfo Alejandro, MD
Phone: 305-243-5324
Click here to add this to my saved trials
