Genetics and Markers of Degenerative and Inflammatory Eye Diseases

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00647439
First received: March 28, 2008
Last updated: March 14, 2014
Last verified: December 2013
  Purpose

This study will identify genes that are associated with inflammation or degeneration of the retina (membrane lining the back of the eye that relays vision signals to the brain). It is thought that many retinal conditions are due to an altered immune system and are based on how the person s genes function and communicate.

People 4 years of age or older who have a retinal condition such as uveitis, age-related macular degeneration or diabetic retinopathy may be eligible for this study. Healthy volunteers and healthy people who have a family member with one of these conditions are also eligible. Patients with inherited retinal degeneration are excluded.

Participants undergo the following tests and procedures:

  • Eye examination to assess visual acuity (eye chart test) and eye pressure, and to examine the pupils, lenses, retina and eye movements. Photographs of the inside of the eye may also be taken. The pupils are dilated with drops for this examination.
  • Blood draw for genetic testing.

Participants may also undergo one or more of the following tests:

  • Optical coherence tomography. This is a type of photograph of the back of the eye to measure thickness of the retina.
  • Fluorescein angiography and indocyanine green angiography. Pictures of the eye s blood vessels are taken using either a fluorescein or indocyanine green dye. The dye is injected into a vein in an arm and travels to the blood vessels in the eyes. A camera takes pictures of the dye as it flows through the blood vessels.
  • Electroretinogram (ERG) to measure retinal function. The patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small metal disk electrode is taped to the forehead, the eye patches are removed, the surface of the eye is numbed with eye drops, and contact lenses are placed on the eyes. The patient then watches flashing lights. The contact lenses sense small electrical signals generated by the retina when the light flashes.

Condition
Diabetic Retinopathy
Age-Related Macular Degeneration (AMD)
Uveitis

Study Type: Observational
Official Title: Epigenetics, Molecular Genetics, and Biomarkers of Degenerative and Inflammatory Ocular Diseases

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Establishing statistically significant evidence for demethyllation differences between patients and controls, linkage between disease and marker loci, association between disease and marker alleles, and causality of disease alleles.

Secondary Outcome Measures:
  • To characterize the effects of identified mutations on the expressed proteins biochemically and physiologically.

Estimated Enrollment: 1000
Study Start Date: March 2008
Detailed Description:

Objective:

This project will study epigenetic mechanisms, the inheritance of (both Mendelian and complex) and biomarkers of Immune Mediated Eye Diseases, in families of many nationalities and ethnic backgrounds in order to identify the genes that, when genetically mutated or epigenetically regulated, cause immune mediated eye disease, and the pathophysiology through which they act.

Study Population: The number of participants to be enrolled has no logical upper limit, but will be at 1,000 during the next 5 years. Race, age and sex matched controls, anonymous volunteers will also be needed to donate a blood sample. The study consists of ascertaining individuals and families with multiple individuals, if possible, affected by immune mediated ocular disease.

Design:

These patients and their families will undergo detailed ophthalmologic examinations and, where indicated, additional non-investigational examinations to characterize their ocular status. A blood sample will be collected from each individual and immunophenotyped using Flow Cytometry. Serum will be isolated for testing serological markers. One or more sub-populations of cells (including but not limited to CD4 plus and CD8 plus T cells, B cells, CD14 plus monocytes, dendritic cells, NK cells, neutrophils and granulocytes) will be isolated. DNA, RNA and chromatin may be isolated for further gene expression profiling and epigenetic studies. Association of genetic or epigenetic changes with ocular inflammatory disease in patients and their families will be identified using one of the techniques including but not limited to DNA-seq, BS-seq, MeDIP-seq, ChIP-seq, RNA-seq, microarray, PCR, and multicolor Flow Cytometry staining. DNA samples from the AREDS study, held under the DCR/NEI Repository protocol (07-EI-0168), will also be used for analysis. If necessary, the gene product or blood sample will be characterized biochemically.

Outcome Measures:

Immunophenotyping, gene expression and epigenetic changes will be reported using Statistical analysis performed using the t test or ANOVA and post-hoc testing with Fisher s least significant difference test. Unless otherwise noted, results are presented as the mean SEM. Biochemical, metabolic, and physiological effects will be individualized to the specific assay

  Eligibility

Ages Eligible for Study:   4 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Participants with the following will be recruited:

  • Individuals or family members of individuals with immune mediated retinal disorders, including uveitis, age related macular degeneration, and diabetic retinopathy.
  • Adults must be capable of providing their own consent.
  • All participants must be able to cooperate with study examination and phlebotomy.
  • Children must be older than 4 years of age.

EXCLUSION CRITERIA:

  • Individuals with diseases, infections, or trauma that mimic immune medicated retinal disorders.
  • Children requiring sedation for study procedures.
  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: NCT00647439

Contacts
Contact: Dominic Obiyor, R.N. (301) 435-4556 dobiyor@mail.nih.gov
Contact: Robert B Nussenblatt, M.D. (301) 496-3123 drbob@nei.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: Robert B Nussenblatt, M.D. National Eye Institute (NEI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00647439     History of Changes
Other Study ID Numbers: 080099, 08-EI-0099
Study First Received: March 28, 2008
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Epigenetics
Biomarkers
Uveitis
Age-Related Macular Degeneration (AMD)
Diabetic Retinopathy
Age-Related Macular Degeneration
AMD

Additional relevant MeSH terms:
Diabetic Retinopathy
Macular Degeneration
Retinal Diseases
Uveitis
Chorioretinitis
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Retinal Degeneration
Uveal Diseases
Retinitis
Choroiditis
Choroid Diseases
Uveitis, Posterior
Panuveitis

ClinicalTrials.gov processed this record on August 28, 2014