Longitudinal Optic Neuritis Study (LONS)



Sponsors


Source

National Eye Institute (NEI)

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.

Overall Status

Unknown status

Start Date

1988-07-01

Completion Date

N/A

Primary Completion Date

N/A

Phase

N/A

Study Type

Interventional


Conditions


Intervention

Intervention Type

Drug

Intervention Name



Intervention Type

Drug

Intervention Name




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

Gender

All

Minimum Age

18 Years

Maximum Age

46 Years

Healthy Volunteers

No


Location

Facility

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

Location Countries

Country

United States


Verification Date

1999-10-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Has Expanded Access

No

Condition Browse


Intervention Browse

Mesh Term

Prednisolone acetate

Methylprednisolone acetate

Prednisone

Methylprednisolone

Methylprednisolone Hemisuccinate

Prednisolone

Prednisolone hemisuccinate

Prednisolone phosphate



Firstreceived Results Date

N/A

Reference

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


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.

PMID

8500302


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.

PMID

8500303


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.

PMID

8932973


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)


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.

PMID

9400788


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.

PMID

1841573


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.

PMID

1734247


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.

PMID

1318520


Citation

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

PMID

1543448


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.

PMID

8352671


Citation

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

PMID

8512477


Citation

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

PMID

8447730


Citation

Beck RW, Cleary PA, Trobe JD, Kaufman DI, Kupersmith MJ, Paty DW, Brown CH. The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis. The Optic Neuritis Study Group. N Engl J Med. 1993 Dec 9;329(24):1764-9.

PMID

8232485


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.

PMID

8493012


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.

PMID

8468765


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.

PMID

8431161


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.

PMID

7800355


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.

PMID

8031275


Citation

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

PMID

7864737


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.

PMID

8574355


Citation

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

PMID

9097798


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.

PMID

8614496


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.

PMID

8610798


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.

PMID

9093956



Firstreceived Results Disposition Date

N/A

Study Design Info

Primary Purpose

Treatment

Masking

Single


Study First Submitted

September 23, 1999

Study First Submitted Qc

September 23, 1999

Study First Posted

September 24, 1999

Last Update Submitted

May 26, 2006

Last Update Submitted Qc

May 26, 2006

Last Update Posted

May 29, 2006

Last Known Status

Active, not recruiting


ClinicalTrials.gov processed this data on August 24, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



© 2018 ICH GCP