Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol

TY - JOUR

T1 - Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol

AU - Diem, Ricarda

AU - Molnar, Fanni

AU - Beisse, Flemming

AU - Gross, Nikolai

AU - Drüschler, Katharina

AU - Heinrich, Sven P

AU - Joachimsen, Lutz

AU - Rauer, Sebastian

AU - Pielen, Amelie

AU - Sühs, Kurt-Wolfram

AU - Linker, Ralf Andreas

AU - Huchzermeyer, Cord

AU - Albrecht, Philipp

AU - Hassenstein, Andrea

AU - Aktas, Orhan

AU - Guthoff, Tanja

AU - Tonagel, Felix

AU - Kernstock, Christoph

AU - Hartmann, Kathrin

AU - Kümpfel, Tania

AU - Hein, Katharina

AU - van Oterendorp, Christian

AU - Grotejohann, Birgit

AU - Ihorst, Gabriele

AU - Maurer, Julia

AU - Volkmann, Martin

AU - Wildemann, Brigitte

AU - Platten, Michael

AU - Wick, Wolfgang

AU - Heesen, Christoph

AU - Schiefer, Ulrich

AU - Wolf, Sebastian

AU - Lagrèze, Wolf A

AU - Müller, Matthias

N1 - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

PY - 2016/3/1

Y1 - 2016/3/1

N2 - INTRODUCTION: Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function.METHODS AND ANALYSIS: Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months.ETHICS AND DISSEMINATION: TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP.TRIAL REGISTRATION NUMBER: NCT01962571.

AB - INTRODUCTION: Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function.METHODS AND ANALYSIS: Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months.ETHICS AND DISSEMINATION: TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP.TRIAL REGISTRATION NUMBER: NCT01962571.

U2 - 10.1136/bmjopen-2015-010956

DO - 10.1136/bmjopen-2015-010956

M3 - SCORING: Journal article

C2 - 26932144

VL - 6

SP - e010956

JO - BMJ OPEN

JF - BMJ OPEN

SN - 2044-6055

IS - 3

ER -