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Pancreatic Islet Transplantation Into the Anterior Chamber of the Eye

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ClinicalTrials.gov Identifier: NCT02846571
Recruitment Status : Not yet recruiting
First Posted : July 27, 2016
Last Update Posted : May 6, 2019
Sponsor:
Collaborators:
Diabetes Research Institute Foundation
Bascom Palmer Eye Institute
Information provided by (Responsible Party):
Midhat H. Abdulreda, University of Miami

Brief 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 45-60 minutes after islet infusion to maximize adhesion of the islets to the iris.

Condition or disease Intervention/treatment Phase
Diabetes Biological: Human Pancreatic Islet Transplantation Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pancreatic Islet Transplantation Into the Anterior Chamber of the Eye
Estimated Study Start Date : June 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Human Pancreatic Islet Transplantation
Islet transplantation into the anterior chamber of the eye single arm
Biological: Human Pancreatic Islet Transplantation
Human Pancreatic Islet Transplantation in the Eye Anterior Chamber of legally blind Diabetic Patients with Stable Kidney Transplantation




Primary Outcome Measures :
  1. Reduction (≥ 50%) of glycemia fluctuations [ Time Frame: 6 months after transplant ]
    Reduction of glucose variability 6 months after transplantation

  2. Reduction (≥ 25%) in exogenous insulin requirements [ Time Frame: 6 months after transplant ]
    Reduction of total insulin requirements 6 months after transplantation

  3. Increased (≥ 1x) unstimulated serum c-peptide (corrected to glycemia) compared to baseline before transplant [ Time Frame: Baseline; 6 months after transplant ]
    Increase of basal c-peptide corrected to glucose values (c-peptide Glucose ratio)

  4. HbA1C ≤ 7% or a ≥ 2.5 decrease from baseline (before transplant) [ Time Frame: Baseline; 1 year after transplant ]
    reduction in A1c below or equal to 7 or a reduction on A1c of more or equal to 2.5



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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. No evidence of advanced or uncontrolled diabetic retinopathy.
  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 age 18 to 70 years of age and no history of non-compliance.
  2. Stable kidney transplant recipient with ongoing immunosuppression.
  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 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; OR HYPO score greater than or equal to the 90th percentile (1047) during the screening period; OR marked glycemic lability characterized by wide swings in BG despite optimal diabetes therapy and defined by an LI score greater than or equal to the 90th percentile (433 mmol/L2/h·wk-1) during the screening period; OR composite of a Clarke score of less than 4 and a HYPO score greater than or equal to the 75th percentile (423) and a LI greater than or equal to the 75th percentile (329) during the screening period.

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 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) >30 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, 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 ≤ 35mL/min/1.73 m2.
  9. Proteinuria (albumin/creatinine ratio or ACr >300mg/dl) of new onset since kidney transplantation.
  10. Calculated panel-reactive anti-HLA antibodies > 50%. Subjects with calculated panel reactive anti-HLA antibodies ≤ 50% will be excluded if any of the following are detected:

    i. Positive cross-match. 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 cross-match.

    iii. Antibodies to the renal donor (i.e. presumed de-novo).

  11. 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.
  12. 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.
  13. Negative screen for Epstein-Barr Virus (EBV) by IgG determination.
  14. Invasive aspergillus, histoplasmosis, and coccidioidomycosis infection within one year prior to study enrollment.
  15. Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin.
  16. Known active alcohol or substance abuse.
  17. 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.
  18. 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%.

  19. Hyperlipidemia despite medical therapy (fasting low-density lipoprotein [LDL] cholesterol > 130 mg/dL, treated or untreated; and/or fasting triglycerides > 200 mg/dL).

22. 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.

23. Treatment with any anti-diabetic medications other than insulin within 4 weeks of enrollment.

24. Use of any investigational agents within 4 weeks of enrollment. 25. Administration of live attenuated vaccine(s) within 2 months of enrollment. 26. Any medical condition that, in the opinion of the investigator, will interfere with the safe participation in the trial.

27. A previous islet transplant. 28. A previous pancreas transplant, unless the graft failed within the first week due to thrombosis, followed by pancreatectomy and the transplant occurred more than 6 months prior to enrollment.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02846571


Contacts
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Contact: Midhat Abdulreda, Ph.D. 305-243-9871 mabdulreda@miami.edu
Contact: Sonia H Yoo, M.D. 305-326-6000 ext 6322 syoo@med.miami.edu

Locations
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United States, Florida
Bascom Palmer Eye Institute Not yet recruiting
Miami, Florida, United States, 33136
Contact: Sonia H. Yoo, M.D.    305-326-6000 ext 6322    syoo@med.miami.edu   
Contact: Jessica Taha, CCRC    305-482-5051    JTaha@med.miami.edu   
Sub-Investigator: Sonia H Yoo, M.D.         
Diabetes Research Institute, University of Miami Miller School of Medicine Not yet recruiting
Miami, Florida, United States, 33136
Contact: Rodolfo Alejandro, M.D.    305-243-5324    ralejand@med.miami.edu   
Contact: David A Baidal, M.D.    (305) 243-7740    dbaidal@med.miami.edu   
Sub-Investigator: Rodolfo Alejandro, M.D.         
Sub-Investigator: David A Baidal, M.D.         
Sponsors and Collaborators
Midhat H. Abdulreda
Diabetes Research Institute Foundation
Bascom Palmer Eye Institute
Investigators
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Principal Investigator: Midhat Abdulreda, Ph.D. University of Miami

Additional Information:
Publications:
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Responsible Party: Midhat H. Abdulreda, Assistant Professor, Diabetes Research Institute, University of Miami
ClinicalTrials.gov Identifier: NCT02846571     History of Changes
Other Study ID Numbers: 20160640
First Posted: July 27, 2016    Key Record Dates
Last Update Posted: May 6, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Midhat H. Abdulreda, University of Miami:
Islet Transplantation
Type 1 Diabetes
Immune Tolerance Induction
Diabetes Complications
Intraocular Transplantation
Eye Anterior Chamber
Kidney Transplantation
Immunosuppression
Type 2 Diabetes