Optic Neuritis Treatment Trial (ONTT)

Multiple Sclerosis Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00000146
• Other study ID #: NEI-47
• Status: Active, not recruiting
• Phase: Phase 3
• First received: September 23, 1999
• Last updated: June 2, 2006
• Start date: July 1988

Study information

• Verified date: October 2003
• Source: National Eye Institute (NEI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 46 Years

Eligibility

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

Study Design

Allocation: Randomized, Masking: Single Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Neuritis
• Optic Neuritis

Intervention

Drug:
• Methylprednisolone

• Prednisone

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Illinois	Chicago	Illinois
United States	Duke University	Durham	North Carolina
United States	Michigan State University	East Lansing	Michigan
United States	University of Florida	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Arkansas	Little Rock	Arkansas
United States	New York University	New York	New York
United States	Wills Eye Hospital	Philadelphia	Pennsylvania
United States	Devers Eye Institute	Portland	Oregon
United States	California Pacific Medical Center	San Francisco	California
United States	Swedish Medical Center	Seattle	Washington
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Eye Institute (NEI)

Country where clinical trial is conducted

United States, 

References & Publications (24)

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. — View 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. — View 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. — View 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. — View Citation

Beck RW, Cleary PA. Optic neuritis treatment trial. One-year follow-up results. Arch Ophthalmol. 1993 Jun;111(6):773-5. — View Citation

Beck RW, Cleary PA. Recovery from severe visual loss in optic neuritis. Arch Ophthalmol. 1993 Mar;111(3):300. — View 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. — View 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. — View Citation

Beck RW, Trobe JD. What we have learned from the Optic Neuritis Treatment Trial. Ophthalmology. 1995 Oct;102(10):1504-8. — View 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. — View Citation

Beck RW. The optic neuritis treatment trial. Implications for clinical practice. Optic Neuritis Study Group. Arch Ophthalmol. 1992 Mar;110(3):331-2. — View Citation

Beck RW. The optic neuritis treatment trial: three-year follow-up results. Arch Ophthalmol. 1995 Feb;113(2):136-7. — View 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

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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)

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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 24 references in all — Click here to view all references

External Links

•   Clinical Alert to Ophthalmologists and Neurologists who Treat Patients with Optic Neuritis
•   NEI Press Release-Corticosteroids for First-Time Optic Neuritis Lowers Risk of Developing Multiple Sclerosis
•   NEI Press Release-Oral Corticosteroids Alone Found Ineffective for Optic Neuritis