Neurofibromatosis Type 1NEF-1NCT04153344
Function of the Pigment Epithelium in Patients With Type 1 Neurofibromatosis
An observational study of Neurofibromatosis Type 1, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 7 years and older
- Conditions the study is for
- Neurofibromatosis Type 1
- What is being tested?
- Electro-oculogram and Full-field electroretinogram
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 11 May 2020to 21 Jul 2020
- 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 7 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Neurofibromatosis Type 1
- Being tested
- Electro-oculogram, Full-field electroretinogram
- Keywords
- Neurofibromatosis type 1, Infrared hyperreflective areas, Hyperactivity of the pigment epithelium, Electro-oculogram, Electroretinogram
- Medical subject headings
- Neurofibromatosis 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Electro-oculogramOther
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.
Full-field electroretinogramOther
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).
| Study group | Role | What they receive |
|---|---|---|
| Infrared hyperreflective area | Patients with neurofibromatosis type 1 and with infrared hyperreflective areas Receives: Other: Electro-oculogram; Other: Full-field electroretinogram | |
| No infrared hyperreflective areas | Patients with neurofibromatosis type 1 and with no infrared hyperreflective areas Receives: Other: Electro-oculogram; Other: Full-field electroretinogram | |
| Controls | Patients with no neurofibromatosis type 1 Receives: Other: Electro-oculogram; Other: Full-field electroretinogram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dark trough value
Electro-oculogram : dark trough value (μV).
Measured: 12 months
Light/dark (Arden) ratio
Electro-oculogram : ratio between the light and dark potentials.
Measured: 12 months
Secondary outcomes (3)
Number and area of infrared hyperreflective areas
Infrared fundus picture.
Measured: 12 months
Values of the amplitudes
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.
Measured: 12 months
Values of the peak times
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2019
- Study start11 May 2020
- Primary completion21 Jul 2020
- Study completion21 Jul 2020
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 Neurofibromatosis Type 1Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Matthieu Robert, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de ParisDominique Brémond-Gignac, MD, PhD, Study director, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04153344
- Sponsor's protocol ID
- APHP190937
- Other IDs
- 2019-A02526-51
- Acronym
- NEF-1
- Status last verified
- Sep 2025
- First submitted
- 4 Nov 2019
- Last updated
- 12 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lubinski W, Zajaczek S, Sych Z, Penkala K, Palacz O, Lubinski J. Electro-oculogram in patients with neurofibromatosis type 1. Doc Ophthalmol. 2001 Sep;103(2):91-103. doi: 10.1023/a:1012271206258.
PubMed 11720259Viola F, Villani E, Natacci F, Selicorni A, Melloni G, Vezzola D, Barteselli G, Mapelli C, Pirondini C, Ratiglia R. Choroidal abnormalities detected by near-infrared reflectance imaging as a new diagnostic criterion for neurofibromatosis 1. Ophthalmology. 2012 Feb;119(2):369-75. doi: 10.1016/j.ophtha.2011.07.046. Epub 2011 Oct 2.
PubMed 21963267Touze R, Abitbol MM, Bremond-Gignac D, Robert MP. Function of the Retinal Pigment Epithelium in Patients With Neurofibromatosis Type 1. Invest Ophthalmol Vis Sci. 2022 Apr 1;63(4):6. doi: 10.1167/iovs.63.4.6.
PubMed 35394491
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Function of the Pigment Epithelium in Patients With Type 1 Neurofibromatosis
- ClinicalTrials.gov ID
- NCT04153344
- Acronym / sponsor ID
- NEF-1 / APHP190937
- Conditions
- Neurofibromatosis Type 1
- Keywords
- Neurofibromatosis type 1, Infrared hyperreflective areas, Hyperactivity of the pigment epithelium, Electro-oculogram, Electroretinogram
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 11 May 2020 (actual)
- Primary completion
- 21 Jul 2020 (actual)
- Study completion
- 21 Jul 2020 (actual)
- First posted
- 6 Nov 2019 (actual)
- 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.
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.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Infrared hyperreflective area | – | Other: Electro-oculogram, Other: Full-field electroretinogramPatients with neurofibromatosis type 1 and with infrared hyperreflective areas |
| No infrared hyperreflective areas | – | Other: Electro-oculogram, Other: Full-field electroretinogramPatients with neurofibromatosis type 1 and with no infrared hyperreflective areas |
| Controls | – | Other: Electro-oculogram, Other: Full-field electroretinogramPatients with no neurofibromatosis type 1 |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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
Key inclusion criteria (6 listed)
- Patients with neurofibromatosis type 1, aged 7 years or older:
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Electro-oculogramElectrophysiological 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 | Controls, Infrared hyperreflective area, No infrared hyperreflective areas |
| Full-field electroretinogramElectrophysiological 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). | Other | Controls, Infrared hyperreflective area, No infrared hyperreflective areas |
Primary outcome
Dark trough value
Time frame: 12 months
Electro-oculogram : dark trough value (μV).
Light/dark (Arden) ratio
Time frame: 12 months
Electro-oculogram : ratio between the light and dark potentials.
3 secondary outcomes
Number and area of infrared hyperreflective areas
Time frame: 12 months
Values of the amplitudes
Time frame: 12 months
Values of the peak times
Time frame: 12 months
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 12 Sep 2025.
- Background: PubMed 11720259Lubinski W, Zajaczek S, Sych Z, Penkala K, Palacz O, Lubinski J. Electro-oculogram in patients with neurofibromatosis type 1. Doc Ophthalmol. 2001 Sep;103(2):91-103. doi: 10.1023/a:1012271206258.
- Background: PubMed 21963267Viola F, Villani E, Natacci F, Selicorni A, Melloni G, Vezzola D, Barteselli G, Mapelli C, Pirondini C, Ratiglia R. Choroidal abnormalities detected by near-infrared reflectance imaging as a new diagnostic criterion for neurofibromatosis 1. Ophthalmology. 2012 Feb;119(2):369-75. doi: 10.1016/j.ophtha.2011.07.046. Epub 2011 Oct 2.
- Results publication: PubMed 35394491Touze R, Abitbol MM, Bremond-Gignac D, Robert MP. Function of the Retinal Pigment Epithelium in Patients With Neurofibromatosis Type 1. Invest Ophthalmol Vis Sci. 2022 Apr 1;63(4):6. doi: 10.1167/iovs.63.4.6.
- Individual participant dataSharing planned: No
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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.
Matthieu Robert, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
Dominique Brémond-Gignac, MD, PhD study director
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neurofibromatosis Type 1, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 3 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 12 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
Dark trough value (time frame: 12 months). The study lists 2 primary outcomes in all. 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 NCT04153344, 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 12 Sep 2025.