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Function of the Pigment Epithelium in Patients With Type 1 Neurofibromatosis (NEF-1)

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ClinicalTrials.gov Identifier: NCT04153344
Recruitment Status : Not yet recruiting
First Posted : November 6, 2019
Last Update Posted : November 19, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

The objective of this study is to study the function of the pigment epithelium in patients with neurofibromatosis type 1 using electro-oculogram to confirm abnormally high values reported in previous studies, but also to correlate this hyperactivity of the pigment epithelium with the presence and size of choroidal hyperreflective areas observed in infra-red imaging of the fundus.

The hypothesis of the study is that the function of the pigment epithelium measured by the electro-oculogram correlates with the surface of choroidal hyperreflective areas. Finally, the potential consequences of a supra-normal function of the pigment epithelium on the global retinal function are not known. A full-field electroretinogram will evaluate the global neurosensory retinal function.


Condition or disease Intervention/treatment
Neurofibromatosis Type 1 Other: Electro-oculogram Other: Full-field electroretinogram

Detailed Description:

Patients with neurofibromatosis type 1 have numerous eye problems: glioma of the optic pathways, Lisch nodules, palpebral involvement by plexiform neurofibromas, orbital dysplasia, etc. With the emergence of multimodal imaging in ophthalmology a new ocular involvement has been described: choroidal hyperreflective areas. They are located in the most superficial layers of the choroid, adjacent to the retinal pigment epithelium, visible only on infra-red imaging of the fundus. These areas are frequently observed, about 90% in adults and 70 to 80% in children. With a sensitivity of 0.83 and a specificity of 0.96, these lesions would have their place as a diagnostic criterion for neurofibromatosis type 1.

In parallel, two successive studies have evaluated the function of the retinal pigment epithelium using electro-oculograms; they showed in patients with neurofibromatosis type 1 a significant increase in the Arden ratio, reflecting hyperactivity of the pigment epithelium.

The objective of this study is to study the function of the pigment epithelium in patients with neurofibromatosis type 1, using electro-oculogram to confirm these abnormally high values, but also to correlate this hyperactivity of the pigment epithelium to the presence and total area of choroidal lesions observed in infra-red imaging of the fundus.

The hypothesis of the study is that the function of the pigment epithelium measured by the electro-oculogram correlates with the surface of the choroidal hyperreflective areas. Finally, the potential consequences of a supra-normal function of the pigment epithelium on the global retinal function are not known. A full-field electroretinogram will evaluate the global neurosensory retinal function.

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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Function of the Pigment Epithelium in Patients With Type 1 Neurofibromatosis
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021


Group/Cohort Intervention/treatment
Infrared hyperreflective area
Patients with neurofibromatosis type 1 and with infrared hyperreflective areas
Other: Electro-oculogram
Electrophysiological recording of changes in electrical potential across the retinal pigmentary epithelium during successive periods of dark and light adaptation, according to ISCEV standards. Results will comprise dark trough value and light/dark (Arden) ratio.

Other: Full-field electroretinogram
Electrophysiological recording of retinal function. Results will comprise amplitudes and latencies of each electroretinography response (dark-adapted 0.01, dark-adapted 3.0, dark-adapted 10.0, dark-adapted 3.0 oscillatory potentials, light-adapted 3.0, light-adapted 3.0 flicker).

No infrared hyperreflective areas
Patients with neurofibromatosis type 1 and with no infrared hyperreflective areas
Other: Electro-oculogram
Electrophysiological recording of changes in electrical potential across the retinal pigmentary epithelium during successive periods of dark and light adaptation, according to ISCEV standards. Results will comprise dark trough value and light/dark (Arden) ratio.

Other: Full-field electroretinogram
Electrophysiological recording of retinal function. Results will comprise amplitudes and latencies of each electroretinography response (dark-adapted 0.01, dark-adapted 3.0, dark-adapted 10.0, dark-adapted 3.0 oscillatory potentials, light-adapted 3.0, light-adapted 3.0 flicker).

Controls
Patients with no neurofibromatosis type 1
Other: Electro-oculogram
Electrophysiological recording of changes in electrical potential across the retinal pigmentary epithelium during successive periods of dark and light adaptation, according to ISCEV standards. Results will comprise dark trough value and light/dark (Arden) ratio.

Other: Full-field electroretinogram
Electrophysiological recording of retinal function. Results will comprise amplitudes and latencies of each electroretinography response (dark-adapted 0.01, dark-adapted 3.0, dark-adapted 10.0, dark-adapted 3.0 oscillatory potentials, light-adapted 3.0, light-adapted 3.0 flicker).




Primary Outcome Measures :
  1. Dark trough value [ Time Frame: 12 months ]
    Electro-oculogram : dark trough value (μV).

  2. Light/dark (Arden) ratio [ Time Frame: 12 months ]
    Electro-oculogram : ratio between the light and dark potentials.


Secondary Outcome Measures :
  1. Number and area of infrared hyperreflective areas [ Time Frame: 12 months ]
    Infrared fundus picture.

  2. Values of the amplitudes [ Time Frame: 12 months ]
    Electroretinogram : values of the amplitudes (μV) of a- and/or b-waves for dark-adapted 0.01, dark adapted 3.0, dark-adapted 10.0, dark-adapted 3.0 oscillatory potentials, light-adapted 3.0, and light-adapted 3.0 flicker.

  3. Values of the peak times [ Time Frame: 12 months ]
    Electroretinogram : values of the peak times (ms) of a- and/or b-waves for dark-adapted 0.01, dark adapted 3.0, dark-adapted 10.0, dark-adapted 3.0 oscillatory potentials, light-adapted 3.0, and value of the peak-to-peak time (ms) for light-adapted 3.0 flicker.



Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients consulting the ophthalmology department of Necker-Enfants Malades Hospital:

  • 10 patients with neurofibromatosis type 1 without infrared hyperreflective areas
  • 10 patients with neurofibromatosis type 1 and infrared hyperreflective areas
  • 10 control patients with no retinal disease
Criteria

Inclusion Criteria:

  • Patients with neurofibromatosis type 1, aged 7 years or older:

    • Presence of hyper-reflective choroidal lesions in infra-red imaging in the group with choroidal lesions.
    • Absence of hyper-reflective choroidal lesions in infra-red imaging in the group without choroidal lesions.
  • Control patients free from retinal or choroidal pathology, matched for age to patients in the group with neurofibromatosis type 1.
  • Patients consulting the ophthalmology department of Necker-Enfants Malades Hospital.
  • Non-opposition of the holders of the parental authority and the minor patient; non-opposition of the major patient.

Exclusion Criteria:

  • Impossibility to perform an electro-oculogram, especially because of an oculomotor disorder, or an electroretinogram, for example because of hyperactivity.
  • Significant impairment of visual function.
  • Retinal pathology proved.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04153344


Contacts
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Contact: Matthieu Robert, MD, PhD +33 1 44 49 53 62 matthieu.robert@aphp.fr
Contact: Hélène Morel +33 1 71 19 63 46 helene.morel@aphp.fr

Locations
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France
Hôpital Necker-Enfants Malades
Paris, France, 75015
Contact: Matthieu Robert, MD, PhD    +33 1 44 49 53 62    matthieu.robert@aphp.fr   
Contact: Hélène Morel    +33 1 71 19 63 46    helene.morel@aphp.fr   
Sub-Investigator: Marc Abitbol, MD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Matthieu Robert, MD, PhD Assistance Publique - Hôpitaux de Paris
Study Director: Dominique Brémond-Gignac, MD, PhD Assistance Publique - Hôpitaux de Paris

Publications:
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04153344    
Other Study ID Numbers: APHP190937
2019-A02526-51 ( Other Identifier: ID RCB )
First Posted: November 6, 2019    Key Record Dates
Last Update Posted: November 19, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Neurofibromatosis type 1
Infrared hyperreflective areas
Hyperactivity of the pigment epithelium
Electro-oculogram
Electroretinogram
Additional relevant MeSH terms:
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Neurofibromatoses
Neurofibromatosis 1
Neurofibroma
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neuromuscular Diseases
Peripheral Nervous System Neoplasms
Nervous System Neoplasms