Optic Neuritis Treatment Trial (ONTT)

• ClinicalTrials.gov Identifier: NCT00000146
• Recruitment Status: Unknown
• First Posted: September 24, 1999
• Last Update Posted: June 5, 2006
• Sponsor: National Eye Institute (NEI)
• Information provided by: National Eye Institute (NEI)

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.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis; Optic Neuritis	Drug: Methylprednisolone; Drug: Prednisone	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Allocation: Randomized
• Masking: Single
• Primary Purpose: Treatment
• Study Start Date: July 1988

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 46 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arkansas

University of Arkansas

Little Rock, Arkansas, United States

United States, California

California Pacific Medical Center

San Francisco, California, United States

United States, District of Columbia

Georgetown University

Washington, District of Columbia, United States

United States, Florida

University of Florida

Gainesville, Florida, United States

United States, Illinois

University of Illinois

Chicago, Illinois, United States

United States, Iowa

University of Iowa

Iowa City, Iowa, United States

United States, Maryland

Johns Hopkins University

Baltimore, Maryland, United States

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States

Michigan State University

East Lansing, Michigan, United States

United States, New York

New York University

New York, New York, United States

United States, North Carolina

Duke University

Durham, North Carolina, United States

United States, Oregon

Devers Eye Institute

Portland, Oregon, United States

United States, Pennsylvania

Wills Eye Hospital

Philadelphia, Pennsylvania, United States

United States, Texas

Baylor College of Medicine

Houston, Texas, United States

United States, Washington

Swedish Medical Center

Seattle, Washington, United States

Sponsors and Collaborators

National Eye Institute (NEI)

More Information

Additional Information:

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 

Publications:

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.

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.

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.

Optic Neuritis Study Group; The five-year risk of multiple sclerosis after optic neuritis. Experience of the Optic Neuritis Treatment Trial., Neurology (in press)

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.

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.

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.

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.

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

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.

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

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

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

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.

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.

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.

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.

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.

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

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.

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

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.

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.

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.

• ClinicalTrials.gov Identifier: NCT00000146 History of Changes
• Other Study ID Numbers: NEI-47
• First Posted: September 24, 1999
• Last Update Posted: June 5, 2006
• Last Verified: October 2003

Additional relevant MeSH terms:

Multiple Sclerosis; Neuritis; Optic Neuritis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases; Prednisone; Methylprednisolone; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Neuroprotective Agents; Protective Agents