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BMJ Open. 2016 Mar 1;6(3):e010956. doi: 10.1136/bmjopen-2015-010956.

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

Author information

1
Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
2
Eye Center, Medical Center-University of Freiburg, Freiburg im Breisgau, Germany.
3
Department of Ophthalmology, Heidelberg University Hospital, Heidelberg, Germany.
4
Department of Neurology and Neuroscience, Medical Center-University of Freiburg, Freiburg im Breisgau, Germany.
5
Clinic for Ophthalmology, Hannover Medical School, Hannover, Germany.
6
Clinic for Neurology, Hannover Medical School, Hannover, Germany.
7
Department of Neurology, University Hospital Erlangen, Erlangen, Germany.
8
Department of Ophthalmology, University Hospital Erlangen, Erlangen, Germany.
9
Department of Neurology, Medical faculty, Heinrich Heine University, Düsseldorf, Germany.
10
Department of Ophthalmology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
11
Department of Ophthalmology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
12
University Eye Hospital Tübingen, Tübingen, Germany.
13
Department of Ophthalmology, University Hospital Munich LMU, Munich, Germany.
14
Department of Neurology, University Hospital Munich, Munich, Germany.
15
Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
16
Department of Ophthalmology, University Medical Center Göttingen, Göttingen, Germany.
17
Clinical Trials Unit, Medical Center-University of Freiburg, Freiburg im Breisgau, Germany.
18
Competence Center "Vision Research", Study Course Ophthalmological Optics, Faculty of Optics and Mechatronics, University of Applied Sciences, Aalen, Germany.
19
Medical Service Center PD Dr. Volkmann and Colleges, Karlsruhe, Germany.
20
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
21
University Eye Hospital Tübingen, Tübingen, Germany Competence Center "Vision Research", Study Course Ophthalmological Optics, Faculty of Optics and Mechatronics, University of Applied Sciences, Aalen, Germany Center for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany.
22
Department of Ophthalmology, Bern Photographic Reading Center, University Hospital and University of Bern, Bern, Switzerland.

Abstract

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.

KEYWORDS:

Erythropoietin; Low Contrast Visual Acuity; Neuroprotection; Optic neuritis; Optical coherence tomography

PMID:
26932144
PMCID:
PMC4785322
DOI:
10.1136/bmjopen-2015-010956
[Indexed for MEDLINE]
Free PMC Article

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