General Information |
| Summary |
Background:
Age-related macular degeneration is a common eye disease in people over 50. The "dry" form of the disease can worsen into geographic atrophy, causing blind spots. Researchers want to learn if replacing older eye cells with younger ones can help treat this disease.
Objective:
To test the safety of putting cells inside the eye as a possible future treatment for dry age-related macular degeneration.
Eligibility:
People ages 55 and older who have geographic atrophy with loss of vision. People who have had "wet" macular degeneration in either eye are NOT eligible.
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Blood and urine tests
- Eye exam
- Eye photos
- Fluorescein angiography. An intravenous (IV) line is placed in an arm vein. A dye is injected. A camera takes pictures of the dye as it flows through the eyes' blood vessels.
- Electroretinography. An electrode is taped to participants' forehead. They sit in the dark. After 30 minutes, numbing eye drops and contact lenses are placed in their eyes. They watch flashing lights.
- Tuberculosis test
- Chest X-ray
- Electrocardiography. Sticky pads are placed on participants' chest to record the heart's electrical activity.
Participants will have at least 14 study visits over 5 and a half years. They will repeat screening tests.
Participants will have retinal pigment epithelium (RPE) transplantation surgery in one eye. For this, cells from participants' blood are turned into RPE cells. These cells are placed in their eye through a cut in their retina. They will get dilating eye drops, an IV line, and anesthesia that may make them sleep. A gas bubble will be put in their eye to help it heal.
Participants will be contacted yearly for up to 15 years. |
| Description |
Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly. There is no treatment for geographic atrophy (GA), the advanced stage of dry AMD, in which cells of the neurosensory retina and associated retinal pigment epithelium (RPE) gradually degenerate and die. Advances in stem cell biology allowing differentiation of pluripotent cells into RPE in vitro make feasible a cell-based strategy for potential treatment of AMD, and recent methods for induced pluripotent stem cell (iPSC) generation offer promise of individualized autologous] therapy. Such an approach involves generation of iPSC from somatic cells taken from a patient with GA, differentiation of iPSC into RPE grown as a monolayer on a thin scaffold in vitro, and transplantation of the RPE/scaffold construct into a small region in the subretinal space of the same patient, with a goal of rescuing the overlying neurosensory retina from further degeneration.
Objective: To evaluate the safety and feasibility of subretinal transplantation of iPSC-derived RPE, grown as a monolayer on a biodegradable poly lactic-co-glycolic acid (PLGA) scaffold, as a potential autologous cell-based therapy for GA associated with AMD.
Study Population: Five participants will undergo RPE transplantation in one eye. Eligible eyes will have GA, best-corrected visual acuity (BCVA) between 20/100 and inclusive of counting fingers (CF), and a fellow eye that has same or better BCVA. If the National Eye Institute (NEI) Data and Safety Monitoring Committee (DSMC) gives clearance to proceed based on review of data from the first cohort, a second cohort of up to seven additional participants with GA, BCVA between 20/80 and CF (inclusive) in the eye being considered for RPE transplantation, and same or better visual acuity in the other eye may undergo the procedure to gather additional safety and potential efficacy data useful for planning future studies. Up to 20 participants may be enrolled to allow for screening failures, for participants withdrawing from the study prior to RPE transplantation, or cases where the RPE cell transplantation does not occur due to intraoperative surgical considerations.
Design: In this phase I/IIa, prospective, single-arm, single-center clinical trial, participants will undergo subretinal transplantation of autologous iPSC-derived RPE in one eye and will be followed for five years after surgery.
Outcome Measures: The primary outcome measure is the safety of RPE/PLGA transplantation, as determined by assessment of visual acuity change and summary of adverse events at 12 months after RPE/PLGA transplantation. Secondary outcome measures include visual acuity change and adverse event reporting at 24 and 60 months, and changes in the following at 12, 24 and 60 months as compared with baseline, assessed in the transplanted region, and compared where applicable with other areas in the macula, and/or with corresponding regions in the fellow eye: retinal sensitivity and fixation parameters assessed by microperimetry; multifocal electroretinography (mfERG) responses; macular structure on cross-sectional and en face imaging by optical coherence tomography (OCT); macular features on color, single-wavelength reflectance, and fundus autofluorescence (FAF) photography; and fluorescein angiography (FA). Some NEI participants may undergo imaging of photoreceptor/RPE features using adaptive-optics-assisted macular imaging under a separate protocol (e.g., 15-EI-0020). |
| Clinical trials phase |
Phases 1/2 |
| Start date (estimated) |
2020-09-23 |
| End date (estimated) |
2029-05-31 |
| Clinical feature |
| Label |
age related macular degeneration |
| Link |
http://purl.obolibrary.org/obo/DOID_10871 |
| Description |
A degeneration of macula and posterior pole that is characterized by a loss of vision in the center of the visual field (the macula) resulting from damage to the retina and resulting in blurring of the sharp central vision.; OMIM mapping confirmed by DO. [SN]. |
|
Administrative Information |
| NCT number |
NCT04339764 |
| ICTRP weblink |
https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04339764 |
| Other study identifiers |
|
| Source weblink |
https://clinicaltrials.gov/ct2/show/study/NCT04339764 |
| Public contact |
| Email |
ellaine.galindez-balut@nih.gov |
| Public email |
ellaine.galindez-balut@nih.gov |
| First name |
Ellaine M |
| Last name |
Galindez-Balut |
| Phone |
+ 1 301 402-4726 |
| Country |
|
|
| Sponsors |
National Eye Institute (NEI)
|
Cells |
| Which differentiated cell type is used |
| Label |
retinal pigment epithelial cell |
| Link |
http://purl.obolibrary.org/obo/CL_0002586 |
| Description |
An epithelial cell of the retinal pigmented epithelium.; This extended description was generated by ChatGPT and reviewed by the CellGuide team, who added references, and by the CL editors, who approved it for inclusion in CL. It may contain information that applies to only to some subtypes and species, and so should not be considered definitional.
Retinal pigment epithelial (RPE) cells form a single layer of cells at the back of the eye sandwiched between the neurosensory retina and the choroid, playing a significant role in maintaining vision health. These pigment-laden cells are highly specialized and perform an array of metabolic and transport functions essential for the maintenance of the photoreceptor cells (rods and cones) in the retina. The pigmentation of RPE cells actively aids in the absorption of excess light and the prevention of light scattering, thus enhancing the eye's optical properties.
The retinal pigment epithelium forms a key part of the blood/retina barrier. The cells have long sheet-like microvilli on their apical membrane that project into the light-sensitive outer segments of the photoreceptors, forming a close structural interaction. The basolateral membrane of the RPE interacts with the underlying Bruch’s membrane, which separates the RPE cells from fenestrated endothelium of the choriocapillaris.
RPE cells support the photoreceptor by providing them with oxygen and nutrients (such as glucose, retinol and fatty acids) and removing waste products. They also recycle the visual pigment, in a process called the "visual cycle", where the RPE cells play a vital role in the regeneration of visual pigment (11-cis retinol) following the absorption of light. This is essential for the maintenance of photoreceptor excitability.
Beyond this, RPE cells take part in the phagocytosis process, where they digest the shed ends of photoreceptor outer segments, thus, preventing the build-up of waste residue that could otherwise harm retinal health. They also secrete various factors, including growth factors required to maintain the structural integrity of choriocapillaris endothelium and photoreceptors, as well as immunosuppressive factors that play an important role in establishing the immune privilege of the eye. |
|
Recruitment |
| Recruitment Status |
Recruiting |
| Estimated number of participants |
20 |
