Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
The treatment in this trial consists of intraocular islet transplantation. A single dose of
1000 - 2000 Islet Equivalents (IEQ)/kg recipient body weight (BW) will be infused into the
anterior chamber of the eye through a self-sealing incision of the peripheral cornea. The
procedure is projected to take approximately 20-30 minutes. Subject will remain flat on their
back for 1-3 hours after islet infusion to maximize adhesion of the islets to the iris.
Phase
Phase 1/Phase 2
Funding Agency/Sponsor
Other
Disease
Diabetes (Type I)
Enrollment Eligibility
Patients who meet all of the following criteria are eligible for participation in the
study:
Ophthalmic inclusion criteria:
1. Patient with at least one eye with extensive loss of vision from hand motion to no
light perception.
2. No evidence of advanced or uncontrolled diabetic retinopathy (i.e., proliferative
D.R).
3. Phakic or pseudophakic with a stable intraocular lens in the blind eye.
4. Normal cornea with good visualization of the anterior segment.
5. Normal anterior segment anatomy including the iris bed.
General and metabolic inclusion criteria:
1. Male and female subjects ages 18 to 70 years of age and no history of non-compliance.
2. Stable kidney function with or without a kidney transplant if applicable.
3. Ability to provide written informed consent.
4. Mentally stable and able to comply with the procedures of the study protocol.
5. Clinical history compatible with T1D with onset of disease at <40 years of age,
insulin-dependence for >5 years at the time of enrollment, and a sum of subject age
and insulin-dependent diabetes duration of ≥23.
6. Absent stimulated c-peptide (<0.3 ng/mL) in response to a mixed meal tolerance test
(MMTT; Boost®Plus 6 mL/kg body weight to a maximum of 360 mL; another product with
equivalent caloric and nutrient content may be substituted for Boost®Plus) measured at
60 and 90 min after the start of consumption.
7. Involvement in intensive diabetes management, defined as self-monitoring of glucose
values no less than a mean of three times each day averaged over each week or by CGM
(continuous glucose monitoring) and by the administration of three or more insulin
injections each day or insulin pump therapy. Such management must be under the
direction of an endocrinologist, diabetologist, or diabetes specialist, with at least
3 clinical evaluations during the 12 months prior to study enrollment.
8. Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more..
9. For islet transplant alone, at least 1 (one) episode of severe hypoglycemia in the 12
months prior to study enrollment; OR time in hypoglycemia range (< 70mg/dL) ≥ 8%
during 24 h as assessed by continuous glucose monitoring.
Patients who meet any of these criteria are not eligible for participation in the study:
Ophthalmic exclusion criteria (only in surgical eye):
1. Poor visualization of the anterior chamber (corneal opacity, corneal edema, Herpes
Keratitis).
2. Aphakic status (no lens).
3. Narrow angle of iris anatomy: Spade Scale IV.
4. History of glaucoma that had required surgical intervention (trabeculectomy, shunting
devices), and uncontrolled glaucoma or neovascularization.
5. History of uveitis.
6. Untreated diabetic retinopathy in either eye.
General and metabolic exclusion criteria:
1. Positive c-peptide.
2. Poor compliance history.
3. Body Mass Index (BMI) >34 kg/m2 or patient weight ≤50 kg.
4. Insulin requirement of >1.0 U/kg/day or <15 U/day.
5. HbA1c >10%.
6. Blood Pressure: SBP >160 mmHg or DBP >100 mmHg.
7. Calculated GFR of ≤40 mL/min/1.73 m2 for islet transplant after kidney or <80
mL/min/1.73 m2 for islet transplant alone, using the subject's measured serum
creatinine and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equation1.
8. Strict vegetarians (vegans) will be excluded only if their estimated GFR is ≤35
mL/min/1.73 m2 for islet transplant after kidney or <70 mL/min/1.73 m2 for islet
transplant alone.
9. Proteinuria (albumin/creatinine ratio or ACr >300mg/dl) of new onset or since kidney
transplantation if applicable.
10. Calculated panel-reactive anti-HLA antibodies > 50% for islet transplant after kidney.
Subjects with calculated panel reactive anti-HLA antibodies ≤ 50% will be excluded if
any of the following are detected:
i. Positive crossmatch. ii. Islet donor-directed anti-HLA antibodies detected by
Luminex Single Antigen specificity bead assay including weakly reactive antibodies
that would not be detected by flow crossmatch.
iii. Antibodies to the renal donor (i.e., presumed de-novo), if applicable.
11. For islet transplant alone, presence or history of panel-reactive anti-HLA antibodies
above background by flow cytometry.
12. For female subjects: 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. Oral contraceptives, Norplant®, Depo-Provera®,
and barrier devices with spermicide are acceptable contraceptive methods; condoms used
alone are not acceptable.
13. Presence or history of active infection including hepatitis B, hepatitis C, HIV, or
tuberculosis (TB). Subjects with laboratory evidence of active infection are excluded
even in the absence of clinical evidence of active infection.
14. Negative screen for Epstein-Barr Virus (EBV) by IgG determination.
15. Invasive aspergillus, histoplasmosis, and coccidioidomycosis infection within one year
prior to study enrollment.
16. Any history of malignancy except for completely resected squamous or basal cell
carcinoma of the skin.
17. Known active alcohol or substance abuse.
18. Baseline 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).
Participants with lymphopenia are allowed if the investigator determines there is no
additional risk and obtains clearance from a hematologist.
19. Severe co-existing cardiac disease, characterized by any one of these conditions:
i. Recent myocardial infarction (within past 6 months). ii. Evidence of ischemia on
functional cardiac exam within the last year. iii. Left ventricular ejection fraction
<30%.
20. Hyperlipidemia despite medical therapy (fasting low-density lipoprotein [LDL]
cholesterol >130 mg/dL, treated or untreated; and/or fasting triglycerides >200
mg/dL).
21. Receiving treatment for a medical condition requiring chronic use of systemic
steroids, except for the use of ≤5 mg prednisone daily, or an equivalent dose of
hydrocortisone, for physiological replacement only.
22. 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. A previous islet transplant.
27. A previous pancreas transplant, unless the graft failed within the first two (2) weeks
due to thrombosis, followed with or without pancreatectomy of graft and the transplant
occurred more than 6 months prior to enrollment.