Natural History of Eye Diseases Related to ABCA4 Mutations
- The ABCA4 gene contains a blueprint for the ABCA4 protein. When this protein is absent or faulty (such as in Stargardt s disease), waste material from dead cells collects in the eye. The waste material may cause other cells in the eye to die. This can lead to the loss of vision. Researchers want to look at blood and skin samples from people with ABCA4 gene mutations to study related eye diseases.
- To study eye diseases that are related to mutations in the ABCA4 gene.
- Individuals at least 12 years of age who have ABCA4 gene mutations.
- The study requires seven visits to the National Eye Institute clinic over 5 years. In the first year, there will be three visits. After the first year, participants will have one visit a year for 4 more years.
- Participants will be screened with a physical exam, full eye exam, and medical history. The eye exam will check eye pressure, light and color sensitivity, and retina function.
- Participants will provide a blood sample and a skin tissue sample for study.
- No treatment will be provided as part of this study.
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Natural History of ABCA4-Related Retinopathies|
- The primary outcome for this study is the establishment of a cohort of participants with ABCA4-related retinopathies. [ Time Frame: Ongoing ]
- Additional, exploratory outlines are listed in the precis. [ Time Frame: Ongoing ]
- The secondary outcome for this study is the creation of a repository of plasma, DNA, and skin fibroblast samples from the accrued cohort of ABCA4-related retinopathy participants. [ Time Frame: Ongoing ]
|Study Start Date:||September 2, 2012|
Objectives: The objectives of this study are to 1) establish a cohort of participants with ABCA4-related retinopathies in anticipation of future clinical trials, 2) create a repository of plasma, DNA, and skin fibroblast samples from the accrued cohort of ABCA4-related retinopathy participants, 3) formulate clinical outcome measures for future studies, and 4) acquire and perform preliminary analyses of data that may advance our understanding of genotype-phenotype correlations in ABCA4-related retinopathies.
In addition, the skin fibroblast samples collected from participants may be used to generate iPS cells, which may be differentiated into RPE and/or neural retinal cells. These cells, if produced, will be used to analyze molecular mechanisms involved in disease pathogenesis and to perform high throughput (HTP) drug screens to identify novel potential therapeutic compounds.
Study Population: Sixty-five (65) participants, age 12 or above, with ABCA4-related retinopathies, including 20 participants with cone-rod dystrophy will be initially accrued for this study. However, up to an additional five participants may be enrolled to replace participants who may withdraw from the study prior to reaching the Month 12 visit.
Design: In this natural history study, participants will be followed for five years. Because three years may be required to enroll 65 participants, this study will last up to eight years. Participants will be recruited through other pre-existing NIH protocols, such as the NEI Evaluation and Treatment Trial (08-EI-0169), the NEI Screening Protocol (08-EI-0102), and the National Ophthalmic Disease Genotyping and Phenotyping Network, Phase II protocol (eyeGENE II, 10-EI-N164), or through referral from an outside clinician after a review of pertinent medical records and genetic testing. All participants will undergo a standardized medical/ophthalmic history and a complete baseline eye examination, including non-invasive electrophysiology (e.g., electroretinography), psychophysiology (e.g., microperimetry, static perimetry), and diagnostic imaging examinations (e.g., optical coherence tomography).
The participants will be examined three times over the course of the first year (i.e., baseline examination, Month 6, and Month 12). After the first year, they will return to the NEI clinic on an annual basis for the next four years. This study will require a minimum of seven study visits. Participants may be seen at more frequent intervals at the investigators discretion, depending on the clinical and research situation. Participants will be required to submit a blood sample as part of the study for DNA and serum banking, and they will have the option to provide a 3 mm punch skin biopsy to facilitate research at a cellular level.
Outcome Measures: The primary outcome for this study is the establishment of a cohort of participants with ABCA4-related retinopathies, and the secondary outcome is the creation of a repository of plasma, DNA, and skin fibroblast samples from the accrued cohort of ABCA4-related retinopathy participants. Exploratory outcomes for this study include: 1) the formulation of clinical outcome measures for future studies and 2) the acquisition and preliminary analysis of data that may advance our understanding of genotype-phenotype correlations in ABCA4-related retinopathies. Potential exploratory outcomes include: 1) the generation of iPS cells from the skin fibroblast samples, 2) the differentiation of the generated iPS cells into RPE and/or neural retinal cells, and 3) the use of the participant-specific RPE and/or neural retinal cells to perform HTP drug screens to identify novel potential therapeutic compounds. The cells obtained in this protocol may be genetically modified and may be used for in vivo research.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01736293
|Contact: Allison T Bamji, R.N.||(301) email@example.com|
|Contact: Brian P Brooks, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Brian P Brooks, M.D.||National Eye Institute (NEI)|