Genetic Decryption of Leber Congenital Amaurosis (LCA) in a Large Cohort of Independent Families. (GENPHENACL)

• ClinicalTrials.gov Identifier: NCT02970266
• Recruitment Status: Completed
• First Posted: November 21, 2016
• Last Update Posted: November 21, 2016
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

The main objectives of this study are:

1. Improve genetic counseling by establishment of prevalences of each of genetic subtypes within a expanded population of patients with LCA taking into account ethnicity of families.
2. Confirm, refine or modify the genotype-phenotype correlations.

3. Edit important recommendations for:

   • The clinical and paraclinical exploration of a new patient based on genotype, especially for extraocular explorations, to book at certain genetic subtypes
   • Prenatal care of a couple.
   • Directing families to a therapeutic protocol in progress or in development.
4. Individualize a panel of families without a mutation in the known genes and identify new genes responsible.

Condition or disease
Leber Congenital Amaurosis

Detailed Description:

This study characterize the clinical history of the disease (age and start mode of visual disturbances, rate and mode of progress of disease), careful assessment of retina function and finally, in search of the mutations responsible for this condition.

A full ophthalmic check-up, one at the inclusion and 24 months :

1. - A genetic consultation taking account of family history and establishment of family tree with precision of geographical origin of birth of ascendants.

2. - A thorough ophthalmologic examination by a referring medical ophthalmologist, including:

   2.1 - An interrogation on the development of the visual awakening since the birth and its possible disturbances.

   2.2 - The search for abnormal movements of the eyeballs, and difficulties with regard to different lighting.

   2.3 - Visual field evaluation Survey.

   2.4 - The study of color vision.

   2.5 - The search for a refractive disorder with the automatic refractometer.

   2.6 - Measurement of Visual acuity for near and distance.

   2.7 - Examination of the eyeball as a whole, examination of the anterior chamber of the eye by the slit lamp.

   2.8 - Taking pictures of the fundus of the eye after pupillary dilation.

   2.9 - An autofluorescence search using a Scanning Laser Ophthalmoscopy (SLO).

   2.10 - Optical Coherence Tomography (OCT) which used to assess the thickness of each of retinal layers.

   2.11 - Electrophysiological examination, Electroretinogram (ERG) that allows to record the functional value of the retina.

   These two latter examinations last on average 10 minutes after dilation of the pupil.

3. - A blood sample of 10 milliliters to carry out genetic studies to identify the gene responsible for this condition and genetic counseling refined by taking account the results of this study.

Intermediate visit M12: only for patients younger than 6 years of age on inclusion.

Study Design

• Study Type: Observational
• Actual Enrollment: 659 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Genetic Decryption of Leber Congenital Amaurosis (LCA) in a Large Cohort of Independent Families: Establishment of Genotype-phenotype Correlations and Updating the Clinical Definition of This Retinal Dystrophy
• Study Start Date: September 2010
• Actual Primary Completion Date: September 2015
• Actual Study Completion Date: November 2016

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Improve genetic counseling by establishment of prevalences of each of genetic subtypes within a expanded population of patients with LCA. [ Time Frame: 24 MONTHS ]

Secondary Outcome Measures :

1. Measurement of visual acuity using the logarithmic scale for children under 5 [ Time Frame: 24 MONTHS ]
2. Measurement of visual acuity using Early Treatment Diabetic Retinopathy Study scale (ETDRS) for far vision [ Time Frame: 24 MONTHS ]
3. The "Parinaud Scale" for near vision (After the age of 6) [ Time Frame: 24 MONTHS ]
4. Visual field evaluation Survey [ Time Frame: 24 MONTHS ]
5. Measurement of refraction by portable automatic refractometer. [ Time Frame: 24 MONTHS ]
6. Screening for color vision abnormalities using "children's boards" of "Ishihara Test" from the age of 3-4. [ Time Frame: 24 MONTHS ]
7. Screening for color vision abnormalities using "regular boards" as soon as learning to read figures from the age of five. [ Time Frame: 24 MONTHS ]
8. Test the color vision deficiency using the " Farnsworth test" in adults and children after the age of 6. [ Time Frame: 24 MONTHS ]
9. The visual field test using the Goldman dome in adults and children aged 6 to 7. [ Time Frame: 24 MONTHS ]
10. Electrophysiological examination using Electroretinogram. [ Time Frame: 24 MONTHS ]

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Patients with Leber Congenital Amaurosis (LCA) taking into account Ethnicity of families.

Criteria

Inclusion Criteria:

Patients:

• Patients of all ages
• Patients with symptoms the day of the first consultation allowing to ask the diagnosis of leber congenital amaurosis.
• Are affiliated to a social health care.
• Written informed consent must be given by patients or holders parental authority for minors.

patients and siblings:

• Signed consent for molecular study by the participant or by holders parental authority for minors.
• Are affiliated to a social health care.

Exclusion Criteria:

• Patients whose exploration has laid differential diagnoses.
• Patients refusing the visits provided for in Protocol.

Contacts and Locations

Locations

France

Necker-Enfants Malades Hospital

Paris, France, 75015

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

• Principal Investigator: Josseline KAPLAN, MD; Necker-Enfants Malades Hospital, 75015 Paris. France

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT02970266
• Other Study ID Numbers: P081257
• First Posted: November 21, 2016
• Last Update Posted: November 21, 2016
• Last Verified: November 2016

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Leber Congenital Amaurosis; Genetic Decryption; The genotype-phenotype correlations; Ethnicity families

Additional relevant MeSH terms:

Blindness; Leber Congenital Amaurosis; Vision Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases