Retinal DegenerationNCT00231010
Molecular Genetics of Retinal Degenerations
An observational study of Retinal Degeneration and Retinitis Pigmentosa, run by National Eye Institute (NEI) at 6 sites in 4 countries.
Trial summary
This multinational study will investigate the inheritance of genetic retinal degeneration in families of different nationalities and ethnic backgrounds in order to identify the genes that, when altered, cause retinal degeneration. The retina is a light-sensitive membrane lining the back part of the eye. Read more about this study
- Who is it for?
- Ages 4 years and olderHealthy volunteers can take part
- Conditions the study is for
- Retinal Degeneration, Retinitis Pigmentosa
- How many people
- 3,549 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 26 Sep 2005to 23 Jun 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Patients that meet diagnostic criteria for specific retinal degenerations will be recruited from the NEI and collaborating clinics.
- Subjects with the following will be recruited:
- Individuals or family members of individuals with Retinal degenerations, either congenital, childhood, or age related.
- Adults must be capable of providing their own consent.
- All subjects must be able to cooperate with study examination and phlebotomy.
- Older than 4 years of age.
Who cannot join
- Diseases, infections, or trauma that mimic primary retinal degenerations.
- Children requiring sedation for study procedures.
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
United States3 sites
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
Harvard Medical School
Boston, Massachusetts, 02115
Cleveland Clinic Foundation Childrens Hospital
Cleveland, Ohio, 44195
About this study
This multinational study will investigate the inheritance of genetic retinal degeneration in families of different nationalities and ethnic backgrounds in order to identify the genes that, when altered, cause retinal degeneration. The retina is a light-sensitive membrane lining the back part of the eye. It relays vision signals to the brain, which the brain interprets into sight. When the retina degenerates, vision is altered and possibly lost. The findings of this study should help improve diagnosis and methods of treatment for these disorders. Participating institutions include: the National Institutes for Health in Bethesda, Maryland; the University of Miami in Florida; the Casey Eye Institute in Portland, Oregon; the Byrd Health Sciences Center in Morgantown, West Virginia; the University of Texas Southwestern Medical School in Dallas, Texas; the University of Tennessee Health Sciences Center in Memphis; the Prasad Eye Institute in Hyderabad, India; National Center of Excellence in Molecular Biology in Lahore, Pakistan; and the Jules Gonin Hospital in Lausanne, Switzerland.
Patients with retinitis pigmentosa and closely related diseases such as Usher syndrome, snowflake vitreoretinal dystrophy and Bietti crystalline dystrophy may be eligible for this study. Participants undergo the following tests and procedures:
- Medical and surgical history, including family history of vision problems.
- Examination to clarify the type of retinal degeneration.
- Eye examination, including tests of color vision, field of vision and ability to see in the dark
- Electroretinogram to test the function of visual cells. For this test, the patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small electrode (silver disk) is taped to the forehead and the eye patches are removed. The surface the eyes is numbed with eye drops, and contact lenses are placed on the eyes. The patient looks inside a large dark globe that emits a series of light flashes. Then a light is turned on inside the globe and more lights flash. The contact lenses sense small electrical signals generated by the retina when the light flashes.
- Hearing tests for patients with a personal or family history of deafness. Tests include an audiogram, ear examination and test of middle ear function. For middle ear function testing, the patient feels a little air pressure change for a moment and hears some tones. Another test requires the patient to sit quietly with electrodes on the head, forehead and earlobes.
- Balance testing, including walking in a straight line, standing with eyes closed in the dark and other tests of coordination, and caloric testing. For the caloric testing, any ear wax in the ear canal is removed before the test begins. Then, electrodes are placed on the skin near the eyes and on the forehead. A small amount of cool (sometimes cold) or warm water is instilled into each ear canal, first one and then the other.
- Blood sample collection for genetic testing.
Read the detailed description
Objective: This project, Molecular Genetics of Retinal Degenerations will study the inheritance of genetic retinal degenerations, both Mendelian and complex, in families of many nationalities and ethnic backgrounds in order to identify the genes that, when mutated, cause retinal degenerations and the pathophysiology through which they act.
Study Population: The number of subjects to be enrolled has no logical upper limit, but will be at least 250 and below 5,000 during the next 5 years. The study consists of ascertaining individuals, and especially families with multiple individuals, affected by retinal degenerations including retinitis pigmentosa (RP) and also other closely related retinal degenerations such as Usher syndrome (USH) and Bietti crystalline dystrophy (BCD).
Design: These patients and their families will undergo detailed ophthalmological examinations and, where indicated, additional non-investigational examinations to characterize their retinal degeneration and determine their affectation status. A blood sample will be collected from each individual for isolation of DNA and in some individuals for lymphoblastoid transformation to establish a renewable source of DNA. Linkage analysis, association analysis, physical mapping, and mutational screening will be carried out to identify the specific gene and the mutations in it that are associated with retinal degenerations in this family. If necessary, the gene product will be characterized biochemically.
Outcome Measures: Linkage will be determines using the lod score method and mutations in specific genes will be assessed using a combination of residue conservation, blosum score, and molecular modeling. Association will be determined using chi-square and Fisher exact tests. Biochemical, metabolic, and physiological effects will be individualized to the specific assay.
- Conditions
- Retinal Degeneration, Retinitis Pigmentosa
- Keywords
- Retnitis Pigmentosa, Retinal Degeneration, Retinitis Pigmentosa, RP, Usher Syndrome, USH, Bietti Crystalline Dystrophy, BCD
- Medical subject headings
- Retinal Degeneration, Retinitis Pigmentosa, Usher Syndromes, Bietti Crystalline Dystrophy
What is being measured
The primary outcome is the main question the study is designed to answer.
V
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2005 (estimated)
- Study start26 Sep 2005
- Study completion23 Jun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Retinal DegenerationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Other
- Enrolment
- 3,549 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Eye Institute (NEI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- James F Hejtmancik, M.D., Principal investigator, National Eye Institute (NEI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00231010
- Sponsor's protocol ID
- 050143
- Other IDs
- 05-EI-0143
- Status last verified
- 23 Jun 2016
- First submitted
- 30 Sep 2005
- Last updated
- 5 Apr 2018
- Results posted
- No
Publications
Smith RJ, Pelias MZ, Daiger SP, Keats B, Kimberling W, Hejtmancik JF. Clinical variability and genetic heterogeneity within the Acadian Usher population. Am J Med Genet. 1992 Aug 1;43(6):964-9. doi: 10.1002/ajmg.1320430612.
PubMed 1415347Keats BJ, Todorov AA, Atwood LD, Pelias MZ, Hejtmancik JF, Kimberling WJ, Leppert M, Lewis RA, Smith RJ. Linkage studies of Usher syndrome type 1: exclusion results from the Usher syndrome consortium. Genomics. 1992 Nov;14(3):707-14. doi: 10.1016/s0888-7543(05)80172-7.
PubMed 1427898Smith RJ, Lee EC, Kimberling WJ, Daiger SP, Pelias MZ, Keats BJ, Jay M, Bird A, Reardon W, Guest M, et al. Localization of two genes for Usher syndrome type I to chromosome 11. Genomics. 1992 Dec;14(4):995-1002. doi: 10.1016/s0888-7543(05)80122-3.
PubMed 1478678
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Molecular Genetics of Retinal Degenerations
- ClinicalTrials.gov ID
- NCT00231010
- Acronym / sponsor ID
- 050143
- Conditions
- Retinal Degeneration, Retinitis Pigmentosa
- Keywords
- Retnitis Pigmentosa, Retinal Degeneration, Retinitis Pigmentosa, RP, Usher Syndrome, USH, Bietti Crystalline Dystrophy, BCD
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 3,549 participants (actual)
- Lead sponsor
- National Eye Institute (NEI)US National Institutes of Health
- Study start
- 26 Sep 2005
- Study completion
- 23 Jun 2016
- First posted
- 3 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This multinational study will investigate the inheritance of genetic retinal degeneration in families of different nationalities and ethnic backgrounds in order to identify the genes that, when altered, cause retinal degeneration. The retina is a light-sensitive membrane lining the back part of the eye. It relays vision signals to the brain, which the brain interprets into sight. When the retina degenerates, vision is altered and possibly lost. The findings of this study should help improve diagnosis and methods of treatment for these disorders. Participating institutions include: the National Institutes for Health in Bethesda, Maryland; the University of Miami in Florida; the Casey Eye Institute in Portland, Oregon; the Byrd Health Sciences Center in Morgantown, West Virginia; the University of Texas Southwestern Medical School in Dallas, Texas; the University of Tennessee Health Sciences Center in Memphis; the Prasad Eye Institute in Hyderabad, India; National Center of Excellence in Molecular Biology in Lahore, Pakistan; and the Jules Gonin Hospital in Lausanne, Switzerland.
Patients with retinitis pigmentosa and closely related diseases such as Usher syndrome, snowflake vitreoretinal dystrophy and Bietti crystalline dystrophy may be eligible for this study. Participants undergo the following tests and procedures:
- Medical and surgical history, including family history of vision problems.
- Examination to clarify the type of retinal degeneration.
- Eye examination, including tests of color vision, field of vision and ability to see in the dark
- Electroretinogram to test the function of visual cells. For this test, the patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small electrode (silver disk) is taped to the forehead and the eye patches are removed. The surface the eyes is numbed with eye drops, and contact lenses are placed on the eyes. The patient looks inside a large dark globe that emits a series of light flashes. Then a light is turned on inside the globe and more lights flash. The contact lenses sense small electrical signals generated by the retina when the light flashes.
- Hearing tests for patients with a personal or family history of deafness. Tests include an audiogram, ear examination and test of middle ear function. For middle ear function testing, the patient feels a little air pressure change for a moment and hears some tones. Another test requires the patient to sit quietly with electrodes on the head, forehead and earlobes.
- Balance testing, including walking in a straight line, standing with eyes closed in the dark and other tests of coordination, and caloric testing. For the caloric testing, any ear wax in the ear canal is removed before the test begins. Then, electrodes are placed on the skin near the eyes and on the forehead. A small amount of cool (sometimes cold) or warm water is instilled into each ear canal, first one and then the other.
- Blood sample collection for genetic testing.
Detailed description
Objective: This project, Molecular Genetics of Retinal Degenerations will study the inheritance of genetic retinal degenerations, both Mendelian and complex, in families of many nationalities and ethnic backgrounds in order to identify the genes that, when mutated, cause retinal degenerations and the pathophysiology through which they act.
Study Population: The number of subjects to be enrolled has no logical upper limit, but will be at least 250 and below 5,000 during the next 5 years. The study consists of ascertaining individuals, and especially families with multiple individuals, affected by retinal degenerations including retinitis pigmentosa (RP) and also other closely related retinal degenerations such as Usher syndrome (USH) and Bietti crystalline dystrophy (BCD).
Design: These patients and their families will undergo detailed ophthalmological examinations and, where indicated, additional non-investigational examinations to characterize their retinal degeneration and determine their affectation status. A blood sample will be collected from each individual for isolation of DNA and in some individuals for lymphoblastoid transformation to establish a renewable source of DNA. Linkage analysis, association analysis, physical mapping, and mutational screening will be carried out to identify the specific gene and the mutations in it that are associated with retinal degenerations in this family. If necessary, the gene product will be characterized biochemically.
Outcome Measures: Linkage will be determines using the lod score method and mutations in specific genes will be assessed using a combination of residue conservation, blosum score, and molecular modeling. Association will be determined using chi-square and Fisher exact tests. Biochemical, metabolic, and physiological effects will be individualized to the specific assay.
Study design
- Observational model
- Family based
- Time perspective
- Other
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Patients that meet diagnostic criteria for specific retinal degenerations will be recruited from the NEI and collaborating clinics.
- Individuals or family members of individuals with Retinal degenerations, either congenital, childhood, or age related.
- Adults must be capable of providing their own consent.
- All subjects must be able to cooperate with study examination and phlebotomy.
- Older than 4 years of age.
Key exclusion criteria (2 listed)
- Diseases, infections, or trauma that mimic primary retinal degenerations.
- Children requiring sedation for study procedures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
V
Time frame: Ongoing
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2018.
- Background: PubMed 1415347Smith RJ, Pelias MZ, Daiger SP, Keats B, Kimberling W, Hejtmancik JF. Clinical variability and genetic heterogeneity within the Acadian Usher population. Am J Med Genet. 1992 Aug 1;43(6):964-9. doi: 10.1002/ajmg.1320430612.
- Background: PubMed 1427898Keats BJ, Todorov AA, Atwood LD, Pelias MZ, Hejtmancik JF, Kimberling WJ, Leppert M, Lewis RA, Smith RJ. Linkage studies of Usher syndrome type 1: exclusion results from the Usher syndrome consortium. Genomics. 1992 Nov;14(3):707-14. doi: 10.1016/s0888-7543(05)80172-7.
- Background: PubMed 1478678Smith RJ, Lee EC, Kimberling WJ, Daiger SP, Pelias MZ, Keats BJ, Jay M, Bird A, Reardon W, Guest M, et al. Localization of two genes for Usher syndrome type I to chromosome 11. Genomics. 1992 Dec;14(4):995-1002. doi: 10.1016/s0888-7543(05)80122-3.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James F Hejtmancik, M.D. principal investigator
National Eye Institute (NEI)
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Retinal Degeneration and Retinitis Pigmentosa, run by National Eye Institute (NEI) at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, China, India, Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
V (time frame: Ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00231010, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2018.