Transplanting pancreatic islets into the eye to treat diabetes

Pancreatic Islet Transplantation Into the Anterior Chamber of the Eye

This study is testing whether putting insulin-producing cells into the eye can help people with type 1 diabetes who also have serious vision problems.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 2 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: University of Miami (Academic / other)
• Drugs / interventions: prednisone
• Locations: 2 sites (Miami, Florida and 1 other locations)
• Trial ID: NCT02846571 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the intraocular transplantation of pancreatic islets to treat diabetes, specifically targeting insulin-dependent patients. A single dose of islet cells will be infused into the anterior chamber of the eye through a minimally invasive procedure. Participants will be monitored for the effectiveness of this approach in achieving immune tolerance and improving glycemic control. The study aims to provide a novel method for insulin replacement in patients with type 1 diabetes and severe vision impairment.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 to 75 with type 1 or type 2 diabetes who are insulin-dependent and have significant vision loss.

Not a fit: Patients with stable vision or those who do not meet the specific ophthalmic and metabolic criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new treatment option for diabetes that reduces the need for insulin injections.

How similar studies have performed: While intraocular islet transplantation is a novel approach, similar studies in islet transplantation have shown promise in other settings.

Eligibility criteria

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. Phakic or pseudophakic with a stable intraocular lens in the blind eye.
3. Normal cornea with good visualization of the anterior segment.
4. Normal anterior segment anatomy including the iris bed.

General and metabolic inclusion criteria:

1. Male and female subjects ages 18 to 75 years of age and no history of non-compliance.
2. Clinical history compatible with T1D or T2D with or without insulin-dependence at the time of enrollment.
3. Stable renal function of native or transplanted kidney if applicable.
4. Ability to provide written informed consent.
5. Mentally stable and able to comply with the procedures of the study protocol.

Exclusion Criteria: 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 uncontrolled glaucoma or glaucoma that had required surgical intervention (e.g., trabeculectomy or shunting devices).
5. Active uncontrolled uveitis.
6. Presence of silicone in the anterior segment after complex diabetic retinopathy surgery.
7. History of allergy to topical steroids and immune-modulatory drugs including CSA and Tacrolimus.

General and metabolic exclusion criteria:

1. HbA1c \>10%.
2. Blood Pressure: SBP \>160 mmHg or DBP \>100 mmHg.
3. Calculated GFR of ≤40 mL/min/1.73 m2 for patients with kidney transplant or \<80 mL/min/1.73 m2 for those without kidney transplant, using the subject's measured serum creatinine and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation1.
4. Strict vegetarians (vegans) will be excluded only if their estimated GFR is ≤35 mL/min/1.73 m2 for patients with kidney transplant or \<70 mL/min/1.73 m2 for those without kidney transplant.
5. Proteinuria (albumin/creatinine ratio or ACr \>300mg/dl) of new onset or since kidney transplantation if applicable.
6. Calculated panel-reactive anti-HLA antibodies \>20%.
7. Positive crossmatch.
8. Antibodies (i.e., presumed de-novo) to the kidney transplant donor, if applicable.
9. 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 (24 months) 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.
10. 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.
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. Active malignancy (cancer) except if successfully treated and declared cancer-free and/or in-remission by the oncologist.
14. Known active alcohol or substance abuse.
15. 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 with additional clearance from a hematologist.
16. Severe co-existing cardiac disease, characterized by any one of these conditions:

    1. Recent myocardial infarction (within past 6 months).
    2. Evidence of ischemia on functional cardiac exam within the last year.
    3. Left ventricular ejection fraction \<30%.
17. Hyperlipidemia despite medical therapy (fasting low-density lipoprotein \[LDL\] cholesterol \>130 mg/dL, treated or untreated; and/or fasting triglycerides \>200 mg/dL) for patients with kidney transplant.
18. 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.
19. Use of any investigational agents within 4 weeks of enrollment.
20. Administration of live attenuated vaccine(s) within 2 months of enrollment.
21. Any medical condition that, in the opinion of the investigator, will interfere with the safe participation in the trial.

Where this trial is running

Miami, Florida and 1 other locations

• Bascom Palmer Eye Institute — Miami, Florida, United States (Recruiting)
• Diabetes Research Institute, University of Miami Miller School of Medicine — Miami, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Midhat H Abdulreda, Ph.D. — University of Miami
• Study coordinator: Midhat H Abdulreda, Ph.D.

Conditions Diabetes; Islet Transplantation; Type 1 Diabetes; Immune Tolerance Induction; Diabetes Complications; Intraocular Transplantation; Eye Anterior Chamber; Kidney Transplantation