Natural History of Eye Diseases Related to ABCA4 Mutations

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
ClinicalTrials.gov Identifier:
NCT01736293
First received: November 27, 2012
Last updated: July 3, 2014
Last verified: June 2014
  Purpose

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.

Condition
Retinal Degeneration
ABCA4-Related Retinopathies

Study Type: Observational
Official Title: Natural History of ABCA4-Related Retinopathies

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The primary outcome for this study is the establishment of a cohort of participants with ABCA4-related retinopathies.

Secondary Outcome Measures:
  • Additional, exploratory outlines are listed in the precis.
  • 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.

Estimated Enrollment: 40
Study Start Date: September 2012
Detailed Description:

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: Forty (40) participants, age 12 or above, with ABCA4-related retinopathies will be accrued for this study.

Design: In this natural history study, participants will be followed for five years. Because three years may be required to enroll 40 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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • NCLUSION CRITERIA:

Participant must be 12 years of age or older.

Participant (or legal guardian) must understand and sign the protocol s informed consent document.

Participant must be able to cooperate with detailed psychophysics and electrophysiology testing.

Participant must be able to provide a blood sample.

Participant has either:

-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).

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01736293

Contacts
Contact: Allison T Bamji, R.N. (301) 451-3437 bamjia@nei.nih.gov
Contact: Brian P Brooks, M.D. (301) 496-3577 brooksb@mail.nih.gov

Locations
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    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Brian P Brooks, M.D. National Eye Institute (NEI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
ClinicalTrials.gov Identifier: NCT01736293     History of Changes
Other Study ID Numbers: 120203, 12-EI-0203
Study First Received: November 27, 2012
Last Updated: July 3, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Retinal Degeneration

Additional relevant MeSH terms:
Retinal Degeneration
Retinal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on July 20, 2014