Multiple SclerosisNCT01851434
Natural History of Optic Neuritis
An observational study of Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 3 sites in 2 countries.
Trial summary
Background: Optic neuritis often is a symptom of multiple sclerosis (MS). Many people who experience optic neuritis are later diagnosed with MS. MS disease activity seen on magnetic resonance imaging (MRI) scans is often greater than that seen in tests given during regular doctor's visits. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Multiple Sclerosis
- How many people
- 8 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 20 Mar 2013to 26 Oct 2017
- 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 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Study population: - Up to 30 participants with unilateral optic neuritis. Recruitment will proceed until 10 participants with a brain MRI suggestive of MS (obtained at any time point during the study) have completed the study. - Up to 15 healthy volunteers, age- and sex-matched to the participants with unilateral optic neuritis and a brain MRI suggestive of MS.
Who may be able to join
- COHORT 1: Unilateral optic neuritis.
- Typical demyelinating optic neuritis based on the best clinical judgment of the investigators.
- Symptom onset within 46 weeks of enrollment OR patients with history of optic neuritis who were followed from symptom onset under a Neuroimmunology Branch natural history or screening protocol.
- For women of childbearing potential, willing to use acceptable forms of contraception (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods (condom or diaphragm) with spermicide or they have undergone surgical sterilization (hysterectomy, tubal ligation, or vasectomy in a partner) for the study duration.
- Able to provide informed consent.
- Willing and able to participate in all aspects of the trial.
Show all 11Show fewer
- COHORT 2: Healthy volunteers.
- No medical history that would interfere with study result interpretation, in the best clinical judgment of the investigators.
- Age greater than or equal to 18 years and less than or equal to 50 years.
- Able to provide informed consent.
- Willing and able to participate in all aspects of the trial.
Who cannot join
- History of signs or symptoms suspicious for MS, in the best clinical judgment of the investigators.
- Pateints-Disease-modifying therapy for MS prior to the onset of the current episode of optic neuritis (excludes oral or intravenous glucocorticoids: Healthy Volunteers - Previous or current use of disease-modifying therapy for MS (excluding oral or intravenous glucocorticoids.
- Previous history of clinical optic neuritis or a systemic disease associated with optic neuritis (e.g. sarcoidosis, lymphoma).
- Current or prior optic neuropathy (e.g. trauma, ischemia, glaucoma, optic nerve drusen).
- Previous history of a retinal disease (e.g. diabetic retinopathy, retinal drusen) other than uveitis.
- Previous history of an ophthalmic disease that in the best judgment of the investigator could affect ophthalmic imaging results.
Show all 13Show fewer
- Previous history of a systemic disease that may mimic MS (e.g. neurosyphilis, neurosarcoidosis, CNS ymphoma, Si(SqrRoot)(Delta)gren s syndrome).
- Previous history of a systemic disease that in the best judgment of the investigator could confound study outcome.
- Current use of a TNF-alpha inhibitor (e.g. etanercept).
- Habitual use of illicit drugs that in the best judgment of the investigators could confound study outcome.
- Pregnant or breast-feeding.
- Unwilling to co-enroll on a Neuroimmunology Branch natural history or screening protocol currently 89-N-0045.
- Contraindication to MRI scanning.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
University of Utah
Salt Lake City, Utah, 84112
About this study
Background:
- Optic neuritis often is a symptom of multiple sclerosis (MS). Many people who experience optic neuritis are later diagnosed with MS. MS disease activity seen on magnetic resonance imaging (MRI) scans is often greater than that seen in tests given during regular doctor's visits. Even though MRI is a helpful tool for studying optic neuritis and MS, more information is needed on how MS symptoms show up on MRI scans. Researchers want to use MRI scans to track changes in the optic nerve after an optic neuritis episode. This approach will help them study the relationship between optic neuritis and MS.
Read more
Objectives:
- To collect more information about the relationship between optic neuritis and multiple sclerosis.
Eligibility:
- Individuals between 18 and 50 years of age who have new optic neuritis.
- Individuals between 18 and 50 years of age who have new symptoms of MS other than optic neuritis.
- Healthy volunteers between 18 and 50 years of age.
Design:
- Participants will be screened with a physical exam and medical history. They may provide blood or urine samples.
- Participants with optic neuritis or other MS symptoms will have a baseline study visit. They will have a physical exam and full eye exam. To look for signs of MS, they will have evoked potential tests to see how the body responds to stimulation. They will also have an MRI scan to study any changes in the brain and optic nerves.
- After the first visit, participants will have steroid treatment for 5 days for the optic neuritis.
- Additional study visits will be given 1, 3, 6, 9, and 12 months after the baseline visit. The tests from the first visit, including the MRI scans, will be repeated at these visits.
- Healthy volunteers will have a baseline study visit. They will have a physical exam and full eye exam. They will have evoked potential tests to see how the body responds to stimulation. They will also have an MRI scan to study any changes in the brain and optic nerves.
- Healthy volunteers will have additional study visits 2 and 11 months after the baseline visit. The tests from the first visit, including the MRI scans, will be repeated at these visits.
Read the detailed description
Objective
The goals of this pilot study are:
- To assess the degree to which subacute changes in clinical, electrophysiological, and imaging measures can robustly predict retinal neuronal loss 12 months after acute optic neuritis.
- To construct a composite score that integrates these subacute changes, can itself robustly predict retinal neuronal loss 12 months after acute optic neuritis, can be validated in future trials, and is likely to be modulated by drugs that promote tissue repair and neuroprotection in multiple sclerosis (MS).
- To evaluate the usefulness of specialized magnetic resonance imaging (MRI) measures of the optic nerve in future clinical trials of drugs designed to promote tissue repair and neuroprotection. The primary hypothesis of the study is that peripapillary retinal nerve fiber layer (RNFL) thickness, which is generally agreed to reflect the integrity of optic nerve axons following optic neuritis, and which can be measured using spectral-domain optical coherence tomography (OCT) in the affected eye 12 months following optic neuritis, can be robustly predicted by changes in RNFL thickness between 1 and 3 months following symptom onset.
Study Population
The following cohorts will be recruited at each of the three study sites:
- Up to 30 participants with acute optic neuritis.
- Up to 15 healthy volunteers who are group-wise age- and sex-matched to the participants with unilateral optic neuritis.
Design
This is a one-year, prospective, multi-cohort, multi-site, pilot natural history study. Data obtained at NIH will be compared and aggregated with data obtained at other study sites, specifically the University of Utah-Moran Eye Center (in Salt Lake City) and Hebrew University-Hadassah Medical Center (in Jerusalem, Israel). Data will be gathered at baseline (optional) and at 1, 3, 6, 9, and 12 months in the patient cohort, and at 1, 3, and 12 months in the healthy volunteers.
Outcome Measures
The primary outcome measure is the RNFL thickness in the affected eye 12 months after optic neuritis.
Secondary outcome measures, all measured at 12 months, include:
- Measures of optic nerve structure: mean cross-sectional optic-nerve area; mean, parallel, and perpendicular diffusivity; and MTR all within the optic nerve lesion as visualized at baseline.
- Measures of brain structure: ventricular volume; T2 lesion volume along the visual pathway both sides considered together.
- Measures of retinal structure: ganglion cell layer + inner plexiform layer thickness in the affected eye.
- Measures of visual function: low-contrast letter acuity; high-contrast letter acuity; Pelli-Robson contrast sensitivity; object-from-motion detection; visual fields; and critical flicker-fusion frequency all in the affected eye.
- Measures of visual physiology: VEP amplitude; VEP latency all in the effected eye.
- Conditions
- Multiple Sclerosis
- Keywords
- OCT, Multiple Sclerosis, Optic Neuritis, Magnetic Resonance Imaging (MRI), Natural History
- Medical subject headings
- Multiple Sclerosis, Optic Neuritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| healthy volunteers | age- and sex-matched to the participants with unilateral optic neuritis and a brain MRI suggestive of MS | |
| Patients with unilateral optic neuritis | Recruitment will proceed until 10 participants with a brain MRI suggestive of MS (obtained at any time point during the study) have completed the study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome measure is the RNFL thickness in the affected eye 12 months after optic neuritis
RNFL thickness in the affected eye 12 months after optic neuritis.
Measured: 12 months after optic neuritis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2013 (estimated)
- Study start20 Mar 2013
- Primary completion5 Sep 2014
- Study completion26 Oct 2017
Why it stopped: The original analyses could not be performed due to data inconsistencies across the study sites.
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 Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Eye Institute (NEI)
- Responsible party
- Sponsor
- Investigators
- Daniel S Reich, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01851434
- Sponsor's protocol ID
- 130104
- Other IDs
- 13-N-0104
- Status last verified
- Sep 2022
- First submitted
- 9 May 2013
- Last updated
- 29 Sep 2022
- Results posted
- No
Publications
Leaney J, Klistorner A, Arvind H, Graham SL. Dichoptic suppression of mfVEP amplitude: effect of retinal eccentricity and simulated unilateral visual impairment. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6549-55. doi: 10.1167/iovs.10-5769. Epub 2010 Jul 29.
PubMed 20671270Klistorner A, Arvind H, Garrick R, Yiannikas C, Paine M, Graham SL. Remyelination of optic nerve lesions: spatial and temporal factors. Mult Scler. 2010 Jul;16(7):786-95. doi: 10.1177/1352458510371408. Epub 2010 Jun 7.
PubMed 20530125Klistorner A, Arvind H, Garrick R, Graham SL, Paine M, Yiannikas C. Interrelationship of optical coherence tomography and multifocal visual-evoked potentials after optic neuritis. Invest Ophthalmol Vis Sci. 2010 May;51(5):2770-7. doi: 10.1167/iovs.09-4577. Epub 2009 Dec 30.
PubMed 20042660
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History of Optic Neuritis
- ClinicalTrials.gov ID
- NCT01851434
- Acronym / sponsor ID
- 130104
- Conditions
- Multiple Sclerosis
- Keywords
- OCT, Multiple Sclerosis, Optic Neuritis, Magnetic Resonance Imaging (MRI), Natural History
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: The original analyses could not be performed due to data inconsistencies across the study sites.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Collaborators
- National Eye Institute (NEI)
- Study start
- 20 Mar 2013 (actual)
- Primary completion
- 5 Sep 2014 (actual)
- Study completion
- 26 Oct 2017 (actual)
- First posted
- 10 May 2013 (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.
Background:
- Optic neuritis often is a symptom of multiple sclerosis (MS). Many people who experience optic neuritis are later diagnosed with MS. MS disease activity seen on magnetic resonance imaging (MRI) scans is often greater than that seen in tests given during regular doctor's visits. Even though MRI is a helpful tool for studying optic neuritis and MS, more information is needed on how MS symptoms show up on MRI scans. Researchers want to use MRI scans to track changes in the optic nerve after an optic neuritis episode. This approach will help them study the relationship between optic neuritis and MS.
Objectives:
- To collect more information about the relationship between optic neuritis and multiple sclerosis.
Eligibility:
- Individuals between 18 and 50 years of age who have new optic neuritis.
- Individuals between 18 and 50 years of age who have new symptoms of MS other than optic neuritis.
- Healthy volunteers between 18 and 50 years of age.
Design:
- Participants will be screened with a physical exam and medical history. They may provide blood or urine samples.
- Participants with optic neuritis or other MS symptoms will have a baseline study visit. They will have a physical exam and full eye exam. To look for signs of MS, they will have evoked potential tests to see how the body responds to stimulation. They will also have an MRI scan to study any changes in the brain and optic nerves.
- After the first visit, participants will have steroid treatment for 5 days for the optic neuritis.
- Additional study visits will be given 1, 3, 6, 9, and 12 months after the baseline visit. The tests from the first visit, including the MRI scans, will be repeated at these visits.
- Healthy volunteers will have a baseline study visit. They will have a physical exam and full eye exam. They will have evoked potential tests to see how the body responds to stimulation. They will also have an MRI scan to study any changes in the brain and optic nerves.
- Healthy volunteers will have additional study visits 2 and 11 months after the baseline visit. The tests from the first visit, including the MRI scans, will be repeated at these visits.
Detailed description
Objective
The goals of this pilot study are:
- To assess the degree to which subacute changes in clinical, electrophysiological, and imaging measures can robustly predict retinal neuronal loss 12 months after acute optic neuritis.
- To construct a composite score that integrates these subacute changes, can itself robustly predict retinal neuronal loss 12 months after acute optic neuritis, can be validated in future trials, and is likely to be modulated by drugs that promote tissue repair and neuroprotection in multiple sclerosis (MS).
- To evaluate the usefulness of specialized magnetic resonance imaging (MRI) measures of the optic nerve in future clinical trials of drugs designed to promote tissue repair and neuroprotection. The primary hypothesis of the study is that peripapillary retinal nerve fiber layer (RNFL) thickness, which is generally agreed to reflect the integrity of optic nerve axons following optic neuritis, and which can be measured using spectral-domain optical coherence tomography (OCT) in the affected eye 12 months following optic neuritis, can be robustly predicted by changes in RNFL thickness between 1 and 3 months following symptom onset.
Study Population
The following cohorts will be recruited at each of the three study sites:
- Up to 30 participants with acute optic neuritis.
- Up to 15 healthy volunteers who are group-wise age- and sex-matched to the participants with unilateral optic neuritis.
Design
This is a one-year, prospective, multi-cohort, multi-site, pilot natural history study. Data obtained at NIH will be compared and aggregated with data obtained at other study sites, specifically the University of Utah-Moran Eye Center (in Salt Lake City) and Hebrew University-Hadassah Medical Center (in Jerusalem, Israel). Data will be gathered at baseline (optional) and at 1, 3, 6, 9, and 12 months in the patient cohort, and at 1, 3, and 12 months in the healthy volunteers.
Outcome Measures
The primary outcome measure is the RNFL thickness in the affected eye 12 months after optic neuritis.
Secondary outcome measures, all measured at 12 months, include:
- Measures of optic nerve structure: mean cross-sectional optic-nerve area; mean, parallel, and perpendicular diffusivity; and MTR all within the optic nerve lesion as visualized at baseline.
- Measures of brain structure: ventricular volume; T2 lesion volume along the visual pathway both sides considered together.
- Measures of retinal structure: ganglion cell layer + inner plexiform layer thickness in the affected eye.
- Measures of visual function: low-contrast letter acuity; high-contrast letter acuity; Pelli-Robson contrast sensitivity; object-from-motion detection; visual fields; and critical flicker-fusion frequency all in the affected eye.
- Measures of visual physiology: VEP amplitude; VEP latency all in the effected eye.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| healthy volunteers | – | –age- and sex-matched to the participants with unilateral optic neuritis and a brain MRI suggestive of MS |
| Patients with unilateral optic neuritis | – | –Recruitment will proceed until 10 participants with a brain MRI suggestive of MS (obtained at any time point during the study) have completed the study. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- - Up to 30 participants with unilateral optic neuritis. Recruitment will proceed until 10 participants with a brain MRI suggestive of MS (obtained at any time point during the study) have completed the study. - Up to 15 healthy volunteers, age- and sex-matched to the participants with unilateral optic neuritis and a brain MRI suggestive of MS.
Key inclusion criteria (11 listed)
- COHORT 1: Unilateral optic neuritis.
- Typical demyelinating optic neuritis based on the best clinical judgment of the investigators.
- Symptom onset within 46 weeks of enrollment OR patients with history of optic neuritis who were followed from symptom onset under a Neuroimmunology Branch natural history or screening protocol.
- For women of childbearing potential, willing to use acceptable forms of contraception (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods (condom or diaphragm) with spermicide or they have undergone surgical sterilization (hysterectomy, tubal ligation, or vasectomy in a partner) for the study duration.
- Able to provide informed consent.
Key exclusion criteria (13 listed)
- History of signs or symptoms suspicious for MS, in the best clinical judgment of the investigators.
- Pateints-Disease-modifying therapy for MS prior to the onset of the current episode of optic neuritis (excludes oral or intravenous glucocorticoids: Healthy Volunteers - Previous or current use of disease-modifying therapy for MS (excluding oral or intravenous glucocorticoids.
- Previous history of clinical optic neuritis or a systemic disease associated with optic neuritis (e.g. sarcoidosis, lymphoma).
- Current or prior optic neuropathy (e.g. trauma, ischemia, glaucoma, optic nerve drusen).
- Previous history of a retinal disease (e.g. diabetic retinopathy, retinal drusen) other than uveitis.
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
The primary outcome measure is the RNFL thickness in the affected eye 12 months after optic neuritis
Time frame: 12 months after optic neuritis
RNFL thickness in the affected eye 12 months after optic neuritis.
Results and safety
The study was stopped early (reason given: The original analyses could not be performed due to data inconsistencies across the study sites.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2022.
- Background: PubMed 20671270Leaney J, Klistorner A, Arvind H, Graham SL. Dichoptic suppression of mfVEP amplitude: effect of retinal eccentricity and simulated unilateral visual impairment. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6549-55. doi: 10.1167/iovs.10-5769. Epub 2010 Jul 29.
- Background: PubMed 20530125Klistorner A, Arvind H, Garrick R, Yiannikas C, Paine M, Graham SL. Remyelination of optic nerve lesions: spatial and temporal factors. Mult Scler. 2010 Jul;16(7):786-95. doi: 10.1177/1352458510371408. Epub 2010 Jun 7.
- Background: PubMed 20042660Klistorner A, Arvind H, Garrick R, Graham SL, Paine M, Yiannikas C. Interrelationship of optical coherence tomography and multifocal visual-evoked potentials after optic neuritis. Invest Ophthalmol Vis Sci. 2010 May;51(5):2770-7. doi: 10.1167/iovs.09-4577. Epub 2009 Dec 30.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Daniel S Reich, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 3 sites in 2 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 11 inclusion and 13 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: stopped early, as of the sponsor's last update on 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Israel. 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 was stopped early (reason given: The original analyses could not be performed due to data inconsistencies across the study sites.). Results are not available in the source record.
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?
The primary outcome measure is the RNFL thickness in the affected eye 12 months after optic neuritis (time frame: 12 months after optic neuritis). 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 NCT01851434, 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 29 Sep 2022.