Natural History of Eye Diseases Related to ABCA4 Mutations
| Status: | Recruiting |
|---|---|
| Conditions: | Ocular |
| Therapuetic Areas: | Ophthalmology |
| Healthy: | No |
| Age Range: | 12 - Any |
| Updated: | 11/4/2018 |
| Start Date: | September 4, 2012 |
| Contact: | Allison T Bamji, R.N. |
| Email: | bamjia@nei.nih.gov |
| Phone: | (301) 451-3437 |
Natural History of ABCA4-Related Retinopathies
Background:
- 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.
Objectives:
- To study eye diseases that are related to mutations in the ABCA4 gene.
Eligibility:
- Individuals at least 12 years of age who have ABCA4 gene mutations.
Design:
- 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.
- 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.
Objectives:
- To study eye diseases that are related to mutations in the ABCA4 gene.
Eligibility:
- Individuals at least 12 years of age who have ABCA4 gene mutations.
Design:
- 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.
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, 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.
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, 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.
- NCLUSION CRITERIA:
1. Participant must be 12 years of age or older.
2. Participant (or legal guardian) must understand and sign the protocol s informed
consent document.
3. Participant must be able to cooperate with detailed psychophysics and
electrophysiology testing.
4. Participant must be able to provide a blood sample.
5. Participant has:
- A maculopathy or retinal degeneration plus two (or more) clear mutations in the ABCA4
gene (ascertained with CLIA-certified testing) that are known to be associated with
retinal disease,
OR
-One clear mutation in ABCA4 associated with a classic presentation of fundus
flavimaculatus/Stargardt macular dystrophy (e.g., flecks, macular atrophy) and no
pathogenic mutation(s) in other genes known to cause macular dystrophy.
OR
-One clear mutation in ABCA4, a cone-rod degeneration and no clearly pathogenic mutation(s)
in other genes known to cause cone-rod degeneration.
EXCLUSION CRITERIA:
Participant has evidence of a systemic condition or ocular disease not related to ABCA4
mutations that would complicate the analysis of psychophysical, electrophysiological, or
imaging data. For example, a participant with advanced diabetes mellitus and significant
diabetic retinopathy may display changes in retinal function that could be related to
either his/her diabetic retinopathy or ABCA4 mutations.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
Phone: 800-411-1222
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