A Phase IV Trial of Neuroprotection with ACTH in Acute Optic Neuritis
- UT Southwestern Ambulatory Services
Patients with their first episode of unilateral acute on will be treated with either 3 days of iV methylprednisolone followed by 11 days of oral prednisone or 15 days of intramuscular (iM) or sub-cutaneous corticotropin (SQ) acthar (aCTH).
This is a single blind, parallel active group, randomized controlled trial in which 60 people with clinically unilateral acute optic neuritis ([LessThanorequalTo] 2 weeks of vision loss; with or without a previous diagnosis of relapsing remitting MS) will be treated with either aCTH or iV methylprednisolone/prednisone for 2 weeks. The primary, secondary, and tertiary outcomes will be as noted above. The assessing physicians will be blinded to treatment to minimize bias. We intend to recruit a target number of 3 participants per month and to complete recruitment within 10 months. This rate of recruitment is estimated on the incidence of optic neuritis among the visits to the Rocky Mountain MS Center, university of Pennsylvania, and the university of Texas Southwestern (tertiary care MS centers with [Greater Than] 6,000 patient visits/year). Participants will be assessed for inclusion/exclusion criteria by their treating neurologist at the Rocky Mountain MS Center (Pi- Dr. Jeffrey Bennett), university of Pennsylvania (Kenneth S. Shindler), or university of Texas Southwestern (Pi x Dr. elliot Frohman), and following informed consent, will be randomized with gender, prior diagnosis of MS, DMT usage (interferons vs. Ga vs. Tysabri/Gilenya vs. no treatment), and time to randomization as binary minimization data. We expect to enroll 20 subjects per institution.
Following informed consent and randomization, participants will receive treatment either high dose methylprednisolone (1000 mg iV qD for 3 days followed by 60 mg oral prednisone daily for 11 days) or acthar (80 u iMor SQ daily for 5 days followed by 40 u iM or SQ daily for 10 days). Clinical follow-up by the treating physician is planned at months 0, 1, 3, and 6. During each visit, eTDRS, low contrast acuity (2.5%), and color vision (Farnsworth D-15) will be assessed. at each visit, the national eye institute 25-item Visual Function Questionnaire with 10-item supplement (version 2000), Modified Fatigue impact Scale, Beck's Depression inventory (BDi-ii) and Multiple Sclerosis Quality of Life-54 instrument (Vickrey; uCLa, 1995) will also be administered. oCT evaluations (onH and macular cube) will be performed at months 0, 1, 3 and 6 months using spectral domain oCT (Cirrus oCT; Carl Zeiss Meditec, Dublin, Ca, uSa). automated visual fields (Humphrey 30-2 SiTa) and fundus photography (to assess for pallor) will be performed at baseline, month 1, month 3 and month 6. MfVeP, mfeRG, and pupillometry will be performed at baseline, month 3 and month 6 in the cohort of patients recruited at the university of Texas Southwestern. The patient's treating neurologist will perform blood tests and MRi evaluations to exclude other causes of optic neuropathy at the initial study visit as part of their routine care.
RnFL edema will be defined as either average RnFL thickness greater than the 95th percentile of the age matched normal database or a ratio of RnFL thickness (affected/fellow eye) greater than 1.1 in any quadrant. The study sites will collect and report data on aes and Saes per standard practice.
a representative at uTSW will determine patient randomization accounting for the variables noted above.
1.Written informed consent must be obtained before any assessment is performed.
2.Male and female patients aged between 18 and 64 years, inclusive.
3.Diagnosis of clinically unilateral acute demyelinating optic neuritis (ADON)
4.Clinical signs and symptoms of ADON starting within the 14 day prior to intended randomization (loss of vision, pain on movement, impairment of color vision).
5.The qualifying episode of optic neuritis must be the first clinical episode of optic neuritis in the affected eye.
6.Able to undergo treatment with intravenous methylprednisolone or Acthar gel.