search
Back to results

Optic Neuritis Treatment Trial (ONTT)

Primary Purpose

Multiple Sclerosis, Optic Neuritis

Status
Unknown status
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Methylprednisolone
Prednisone
Sponsored by
National Eye Institute (NEI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis

Eligibility Criteria

18 Years - 46 Years (Adult)All SexesDoes not accept healthy volunteers

The major eligibility criteria for enrollment into the ONTT included the following: Age range of 18 to 46 years Acute unilateral optic neuritis with visual symptoms for 8 days or less A relative afferent pupillary defect and a visual field defect in the affected eye No previous episodes of optic neuritis in the affected eye No previous corticosteroid treatment for optic neuritis or multiple sclerosis No systemic disease other than multiple sclerosis that might be the cause of the optic neuritis

Sites / Locations

  • University of Arkansas
  • California Pacific Medical Center
  • Georgetown University
  • University of Florida
  • University of Illinois
  • University of Iowa
  • Johns Hopkins University
  • University of Michigan
  • Michigan State University
  • New York University
  • Duke University
  • Devers Eye Institute
  • Wills Eye Hospital
  • Baylor College of Medicine
  • Swedish Medical Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
September 23, 1999
Last Updated
June 2, 2006
Sponsor
National Eye Institute (NEI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00000146
Brief Title
Optic Neuritis Treatment Trial (ONTT)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2003
Overall Recruitment Status
Unknown status
Study Start Date
July 1988 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Eye Institute (NEI)

4. Oversight

5. Study Description

Brief Summary
To assess the beneficial and adverse effects of corticosteroid treatment for optic neuritis. To determine the natural history of vision in patients who suffer optic neuritis. To identify risk factors for the development of multiple sclerosis in patients with optic neuritis.
Detailed Description
Optic neuritis is an inflammatory disease of the optic nerve that typically affects young adults. Women are affected more often than men. It is second only to glaucoma as the most common acquired optic nerve disorder in persons younger than age 50. In this disorder, closely linked to multiple sclerosis, prognosis for visual recovery is generally good. However, return of visual function is almost never complete. After resolution of optic neuritis, virtually all patients show some signs of optic nerve damage, and most are symptomatic. Even when a patient's acuity recovers to 20/20, abnormalities frequently remain in other measures such as contrast sensitivity, color vision, and visual field. Prior to the Optic Neuritis Treatment Trial (ONTT), well-established guidelines for treating optic neuritis did not exist. Although corticosteroids had been used to treat this disease, studies to demonstrate their effectiveness had not been satisfactory. Some experts advocated treatment with oral prednisone while others recommended no treatment. Anecdotal reports suggested that high-dose intravenous corticosteroids might be effective. The association between optic neuritis and multiple sclerosis is well established. Optic neuritis may be the first manifestation of multiple sclerosis, or it may occur later in its course. A strong case can be made for "isolated" optic neuritis being a forme fruste of multiple sclerosis, based on similarities between the two in such epidemiologic factors as gender, age, geographic distributions, cerebrospinal fluid changes, histocompatibility data, magnetic resonance imaging (MRI) changes, and family history. The magnitude of the risk of multiple sclerosis after optic neuritis is uncertain. Previous studies have reported very disparate results, with the risk being reported to be as low as 13 percent and as high as 88 percent. The importance of risk factors such as age, gender, and MRI changes in predicting which patients with optic neuritis are most likely to develop multiple sclerosis also is unclear. The treatment phase of the study was called the Optic Neuritis Treatment Trial (ONTT), whereas the current long-term followup phase is called the Longitudinal Optic Neuritis Study (LONS). The study is being conducted at 15 clinical centers in the United States. Resource centers include a data coordinating center and a visual field reading center. Patients were randomized to one of the three following treatment groups at 15 clinical centers: Oral prednisone (1 mg/kg/day) for 14 days Intravenous methylprednisolone (250 mg every 6 hours) for 3 days, followed by oral prednisone (1 mg/kg/day) for 11 days Oral placebo for 14 days Each regimen was followed by a short oral taper. The oral prednisone and placebo groups were double masked, whereas the intravenous methylprednisolone group was single masked. Baseline testing included blood tests to evaluate for syphilis and systemic lupus erythematosus, a chest x-ray to evaluate for sarcoidosis, and a brain MRI scan to evaluate for changes suggestive of multiple sclerosis. The rate of visual recovery and the long-term visual outcome were both assessed by measures of visual acuity, contrast sensitivity, color vision, and visual field at baseline, at seven followup visits during the first 6 months, and then yearly. A standardized neurologic examination with an assessment of multiple sclerosis status was made at baseline, after 6 months, and then yearly.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Optic Neuritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Masking
Single
Allocation
Randomized

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Intervention Type
Drug
Intervention Name(s)
Prednisone

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
46 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
The major eligibility criteria for enrollment into the ONTT included the following: Age range of 18 to 46 years Acute unilateral optic neuritis with visual symptoms for 8 days or less A relative afferent pupillary defect and a visual field defect in the affected eye No previous episodes of optic neuritis in the affected eye No previous corticosteroid treatment for optic neuritis or multiple sclerosis No systemic disease other than multiple sclerosis that might be the cause of the optic neuritis
Facility Information:
Facility Name
University of Arkansas
City
Little Rock
State/Province
Arkansas
Country
United States
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
Country
United States
Facility Name
Georgetown University
City
Washington
State/Province
District of Columbia
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
Country
United States
Facility Name
University of Illinois
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
Country
United States
Facility Name
Michigan State University
City
East Lansing
State/Province
Michigan
Country
United States
Facility Name
New York University
City
New York
State/Province
New York
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
Devers Eye Institute
City
Portland
State/Province
Oregon
Country
United States
Facility Name
Wills Eye Hospital
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
Country
United States
Facility Name
Swedish Medical Center
City
Seattle
State/Province
Washington
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8500302
Citation
Cleary PA, Beck RW, Anderson MM Jr, Kenny DJ, Backlund JY, Gilbert PR. Design, methods, and conduct of the Optic Neuritis Treatment Trial. Control Clin Trials. 1993 Apr;14(2):123-42. doi: 10.1016/0197-2456(93)90015-6.
Results Reference
background
PubMed Identifier
8500303
Citation
Keltner JL, Johnson CA, Beck RW, Cleary PA, Spurr JO. Quality control functions of the Visual Field Reading Center (VFRC) for the Optic Neuritis Treatment Trial (ONTT). Control Clin Trials. 1993 Apr;14(2):143-59. doi: 10.1016/0197-2456(93)90016-7.
Results Reference
background
PubMed Identifier
8932973
Citation
Anderson MM Jr, Boly LD, Beck RW. Remote clinic/patient monitoring for multicenter trials. Optic Neuritis Study Group. Control Clin Trials. 1996 Oct;17(5):407-14. doi: 10.1016/s0197-2456(96)00021-9.
Results Reference
background
Citation
Optic Neuritis Study Group; The five-year risk of multiple sclerosis after optic neuritis. Experience of the Optic Neuritis Treatment Trial., Neurology (in press)
Results Reference
background
PubMed Identifier
9400788
Citation
Visual function 5 years after optic neuritis: experience of the Optic Neuritis Treatment Trial. The Optic Neuritis Study Group. Arch Ophthalmol. 1997 Dec;115(12):1545-52.
Results Reference
background
PubMed Identifier
1841573
Citation
The clinical profile of optic neuritis. Experience of the Optic Neuritis Treatment Trial. Optic Neuritis Study Group. Arch Ophthalmol. 1991 Dec;109(12):1673-8. doi: 10.1001/archopht.1991.01080120057025.
Results Reference
background
PubMed Identifier
1734247
Citation
Beck RW, Cleary PA, Anderson MM Jr, Keltner JL, Shults WT, Kaufman DI, Buckley EG, Corbett JJ, Kupersmith MJ, Miller NR, et al. A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group. N Engl J Med. 1992 Feb 27;326(9):581-8. doi: 10.1056/NEJM199202273260901.
Results Reference
background
PubMed Identifier
1318520
Citation
Beck RW. Corticosteroid treatment of optic neuritis: a need to change treatment practices. The Optic Neuritis Study Group. Neurology. 1992 Jun;42(6):1133-5. doi: 10.1212/wnl.42.6.1133. No abstract available.
Results Reference
background
PubMed Identifier
1543448
Citation
Beck RW. The optic neuritis treatment trial. Implications for clinical practice. Optic Neuritis Study Group. Arch Ophthalmol. 1992 Mar;110(3):331-2. doi: 10.1001/archopht.1992.01080150029020. No abstract available.
Results Reference
background
PubMed Identifier
8352671
Citation
Beck RW, Arrington J, Murtagh FR, Cleary PA, Kaufman DI. Brain magnetic resonance imaging in acute optic neuritis. Experience of the Optic Neuritis Study Group. Arch Neurol. 1993 Aug;50(8):841-6. doi: 10.1001/archneur.1993.00540080050013.
Results Reference
background
PubMed Identifier
8512477
Citation
Beck RW, Cleary PA. Optic neuritis treatment trial. One-year follow-up results. Arch Ophthalmol. 1993 Jun;111(6):773-5. doi: 10.1001/archopht.1993.01090060061023.
Results Reference
background
PubMed Identifier
8447730
Citation
Beck RW, Cleary PA. Recovery from severe visual loss in optic neuritis. Arch Ophthalmol. 1993 Mar;111(3):300. doi: 10.1001/archopht.1993.01090030018009. No abstract available.
Results Reference
background
Citation
Beck RW; Diehl L; Cleary PA; Optic Neuritis Study Group; The Pelli-Robson Letter Chart: Normative data for young adults., Clin Vis Sci 1993;8:207-210
Results Reference
background
PubMed Identifier
8493012
Citation
Beck RW, Kupersmith MJ, Cleary PA, Katz B. Fellow eye abnormalities in acute unilateral optic neuritis. Experience of the optic neuritis treatment trial. Ophthalmology. 1993 May;100(5):691-7; discussion 697-8. doi: 10.1016/s0161-6420(13)31589-9.
Results Reference
background
PubMed Identifier
8468765
Citation
Chrousos GA, Kattah JC, Beck RW, Cleary PA. Side effects of glucocorticoid treatment. Experience of the Optic Neuritis Treatment Trial. JAMA. 1993 Apr 28;269(16):2110-2.
Results Reference
background
PubMed Identifier
8431161
Citation
Keltner JL, Johnson CA, Spurr JO, Beck RW. Baseline visual field profile of optic neuritis. The experience of the optic neuritis treatment trial. Optic Neuritis Study Group. Arch Ophthalmol. 1993 Feb;111(2):231-4. doi: 10.1001/archopht.1993.01090020085029.
Results Reference
background
PubMed Identifier
7800355
Citation
Beck RW, Cleary PA, Backlund JC. The course of visual recovery after optic neuritis. Experience of the Optic Neuritis Treatment Trial. Ophthalmology. 1994 Nov;101(11):1771-8. doi: 10.1016/s0161-6420(94)31103-1.
Results Reference
background
PubMed Identifier
8031275
Citation
Keltner JL, Johnson CA, Spurr JO, Beck RW. Visual field profile of optic neuritis. One-year follow-up in the Optic Neuritis Treatment Trial. Arch Ophthalmol. 1994 Jul;112(7):946-53. doi: 10.1001/archopht.1994.01090190094027.
Results Reference
background
PubMed Identifier
7864737
Citation
Beck RW. The optic neuritis treatment trial: three-year follow-up results. Arch Ophthalmol. 1995 Feb;113(2):136-7. doi: 10.1001/archopht.1995.01100020014004. No abstract available.
Results Reference
background
PubMed Identifier
8574355
Citation
Beck RW, Trobe JD. The Optic Neuritis Treatment Trial. Putting the results in perspective. The Optic Neuritis Study Group. J Neuroophthalmol. 1995 Sep;15(3):131-5. No abstract available.
Results Reference
background
PubMed Identifier
9097798
Citation
Beck RW, Trobe JD. What we have learned from the Optic Neuritis Treatment Trial. Ophthalmology. 1995 Oct;102(10):1504-8. doi: 10.1016/s0161-6420(95)30839-1. No abstract available.
Results Reference
background
PubMed Identifier
8614496
Citation
Rolak LA, Beck RW, Paty DW, Tourtellotte WW, Whitaker JN, Rudick RA. Cerebrospinal fluid in acute optic neuritis: experience of the optic neuritis treatment trial. Neurology. 1996 Feb;46(2):368-72. doi: 10.1212/wnl.46.2.368.
Results Reference
background
PubMed Identifier
8610798
Citation
Trobe JD, Beck RW, Moke PS, Cleary PA. Contrast sensitivity and other vision tests in the optic neuritis treatment trial. Am J Ophthalmol. 1996 May;121(5):547-53. doi: 10.1016/s0002-9394(14)75429-7.
Results Reference
background
PubMed Identifier
9093956
Citation
Cleary PA, Beck RW, Bourque LB, Backlund JC, Miskala PH. Visual symptoms after optic neuritis. Results from the Optic Neuritis Treatment Trial. J Neuroophthalmol. 1997 Mar;17(1):18-23; quiz 24-8. doi: 10.1016/s0002-9394(14)70814-1.
Results Reference
background
PubMed Identifier
35044445
Citation
Solli E, Doshi H, Elze T, Pasquale L, Wall M, Kupersmith M. Archetypal Analysis Reveals Quantifiable Patterns of Visual Field Loss in Optic Neuritis. Transl Vis Sci Technol. 2022 Jan 3;11(1):27. doi: 10.1167/tvst.11.1.27.
Results Reference
derived
Links:
URL
http://www.nei.nih.gov/news/clinicalalerts/alert-ontt.asp
Description
Clinical Alert to Ophthalmologists and Neurologists who Treat Patients with Optic Neuritis
URL
http://www.nei.nih.gov/news/pressreleases/onttpressrelease.asp
Description
NEI Press Release-Corticosteroids for First-Time Optic Neuritis Lowers Risk of Developing Multiple Sclerosis
URL
http://www.nei.nih.gov/news/pressreleases/ontt-1pressrelease.asp
Description
NEI Press Release-Oral Corticosteroids Alone Found Ineffective for Optic Neuritis

Learn more about this trial

Optic Neuritis Treatment Trial (ONTT)

We'll reach out to this number within 24 hrs