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Wolf Lagrèze, Ricarda Diem, TONE-Study group; The design of a randomized clinical trial on the neuroprotective properties of erythropoietin in optic neuritis: Treatment of Optic Neuritis with Erythropoietin (TONE). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5538.
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© ARVO (1962-2015); The Authors (2016-present)
After successful completion of the VISION PROTECT pilot trial (NCT00355095) providing the first morphologic OCT-based evidence for neuroprotection with erythropoietin in optic neuritis, the German government has recently approved a subsequent, full-scale, nationwide randomized controlled clinical trial (NCT01962571), whose design we intend to present here.
A power analysis based on publications on the natural course and thinning of the peripapillary retinal nerve fiber layer after optic neuritis yielded a number of 47 patients in each treatment arm of a placebo-controlled, randomized, double-blind clinical trial to demonstrate a treatment effect of 50% reduction of nerve fiber loss with an α of 0.05 and β of 0.80.
Recruitment of TONE has commenced in December 2014. Patients are randomized on either i.v. placebo or intravenous 33.000 IU i.v. erythropoietin as an add-on to a 3 day course of i.v. megadose methylprednisolone. Primary outcome measure is the peripapillary retinal nerve fiber layer thickness determined with the NSITE 6.0 software of the Spectralis®-OCT. Secondary analyses comprise retinal layer segmentation. Functional measures are ETDRS-chart based visual acuity at 2.5% and 100% contrast, contrast sensitivity, volumetric analysis of the visual field defect determined by the German Adaptive Threshold Estimation (GATE) algorithm, VEP-latencies and vision-related quality of life. Results are expected after completion presumably in 2017. A 1.5 year open label follow-up shall provide further insights of erythropoietin effects with regard to MS-progression.
A positive outcome of the TONE-Trial would not only provide new treatment options for patients with optic neuritis, but might promote further clinical research in multiple sclerosis.
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