Treatment of Optic Neuritis With Erythropoietin: a Randomised, Double-blind, Placebo-controlled Trial

NCT ID: NCT01962571

Last Updated: 2019-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

108 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-11-25

Study Completion Date

2019-11-26

Brief Summary

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This clinical trial aims at preventing visual dysfunction and optic nerve degeneration associated with autoimmune optic neuritis by systemic i.v. administration of 33.000 IU erythropoietin over 3 days. The primary objective is to determine the efficacy of erythropoietin compared to placebo given as add-on to methylprednisolone as assessed by measurements of retinal nerve fibre layer thickness and low contrast visual acuity 6 months after acute optic neuritis.

Detailed Description

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Conditions

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Optic Neuritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Erythropoietin alfa

Recombinant human EPO (Epoetin alfa HEXAL®) will be given as an i.v. bolus injection on days 1, 2 and 3. The dosage per day will be 33.000 IU in accordance with previous trials.

Group Type EXPERIMENTAL

Erythropoietin alfa

Intervention Type DRUG

Placebo

As matched placebo for this study, sterile normal saline (0.9% sodium chloride for i.v. administration) will be used. It will be given as a bolus injection in the same manner as EPO.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

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Erythropoietin alfa

Intervention Type DRUG

Placebo

Intervention Type DRUG

Other Intervention Names

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Saline

Eligibility Criteria

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Inclusion Criteria

1. Written informed consent obtained according to international guidelines and local laws
2. Male and female patients aged ≥ 18 to ≤ 50 years
3. Patients with ON
4. First symptoms of ON ≤ 10 days prior to the first administration of investigational product
5. High contrast visual acuity (HCVA) of ≤ 0.5 (decimal system)
6. Adequate OCT measurements available

Patients eligible for this trial must not meet any of the following criteria:

1. Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial
2. Simultaneous participation in another interventional trial which could interfere with this trial and/or participation in a clinical trial within the last 3 months before enrolment in this trial
3. Refractive anomalies: Hyperopia \> 5 dpt, myopia \< -7 dpt, astigmatism \> 3 dpt
4. Media opacity
5. Severe papillitis
6. Previous ON
7. Any other optic nerve and retinal disease
8. Pre-existing MS or any other neurological disease
9. Congenital diseases:

* thrombophilia
* phenylketonuria
10. Acquired diseases:

* autoimmune diseases,
* cardiovascular diseases,
* diabetes mellitus,
* uncontrolled hypertension (with blood pressure \> 140 / 90 mm Hg (cf. chapter 7.7.5)),
* any malignancy,
* epilepsy,
* known tuberculosis with ongoing or unknown activity,
* acute gastrointestinal ulceration within the last 3 months prior to randomisation,
* acute viral, bacterial or fungal infection,
* known infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus, or Hepatitis C Virus,
* history of colitis ulcerosa, diverticulitis, or acute enteroanastomosis,
* known osteoporosis,
* history of thromboembolic events,
* elevated haemoglobin level (\>17 g/dl in men or \>15 g/dl in women)
* polycythaemia
* any other significant illness potentially interfering with any trial assessment or trial treatment
11. Performing semi-professional or professional sporting activities or physical training
12. Pre-treatment with corticosteroids in the last 30 days prior to the onset of optic neuritis
13. Pre-treatment with EPO
14. Known or persistent abuse of medication, drugs or alcohol
15. Active immunization within 2 weeks prior to randomisation
16. Significant surgery within 4 weeks prior to randomisation
17. Blood donation or bloodletting within 4 weeks prior to screening
18. Pre-treatment with immunosuppressive or immunomodulatory agents
19. Persons who are in a relationship of dependence/employment with the sponsor or the investigator

This section concerns only female patients who are able to have a child:
20. Current or planned pregnancy; nursing period within 3 months from investigational product administration
21. Unwillingness to use one of the following safe combination methods of contraception within 3 months from investigational product administration to achieve a PEARL index of \<1: female condom, diaphragm or coil, each used in combination with a spermicide; hormonal intra-uterine device or hormonal contraception in combination with a mechanical method of contraception
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role collaborator

University Eye Hospital, Freiburg

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. Wolf Lagrèze

Prof. Dr. med.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Wolf A. Lagrèze, Prof.

Role: PRINCIPAL_INVESTIGATOR

Eye Hospital, Medical Center - University of Freiburg

Locations

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Medical Center - University of Freiburg, Eye Hospital

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Site Status

Heidelberg University Hospital, Department of Neurooncology

Heidelberg, Baden-Wurttemberg, Germany

Site Status

Tuebingen University Hospital

Tübingen, Baden-Wurttemberg, Germany

Site Status

University Hospital Erlangen

Erlangen, Bavaria, Germany

Site Status

University Hospital of Munich

Munich, Bavaria, Germany

Site Status

University Hospital Klinikum rechts der Isar, Munich

Munich, Bavaria, Germany

Site Status

University Medical Center Göttingen

Göttingen, Lower Saxony, Germany

Site Status

Hannover Medical School

Hanover, Lower Saxony, Germany

Site Status

Duesseldorf University Hospital

Düsseldorf, North Rhine-Westphalia, Germany

Site Status

University Medical Center of the Johannes Gutenberg University Mainz

Mainz, Rhineland-Palatinate, Germany

Site Status

University Medical Center Hamburg-Eppendorf

Hamburg, , Germany

Site Status

Countries

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Germany

References

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Suhs KW, Hein K, Sattler MB, Gorlitz A, Ciupka C, Scholz K, Kasmann-Kellner B, Papanagiotou P, Schaffler N, Restemeyer C, Bittersohl D, Hassenstein A, Seitz B, Reith W, Fassbender K, Hilgers R, Heesen C, Bahr M, Diem R. A randomized, double-blind, phase 2 study of erythropoietin in optic neuritis. Ann Neurol. 2012 Aug;72(2):199-210. doi: 10.1002/ana.23573.

Reference Type BACKGROUND
PMID: 22926853 (View on PubMed)

Diem R, Molnar F, Beisse F, Gross N, Druschler K, Heinrich SP, Joachimsen L, Rauer S, Pielen A, Suhs KW, Linker RA, Huchzermeyer C, Albrecht P, Hassenstein A, Aktas O, Guthoff T, Tonagel F, Kernstock C, Hartmann K, Kumpfel T, Hein K, van Oterendorp C, Grotejohann B, Ihorst G, Maurer J, Muller M, Volkmann M, Wildemann B, Platten M, Wick W, Heesen C, Schiefer U, Wolf S, Lagreze WA. Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol. BMJ Open. 2016 Mar 1;6(3):e010956. doi: 10.1136/bmjopen-2015-010956.

Reference Type BACKGROUND
PMID: 26932144 (View on PubMed)

Kuchlin S, Ihorst G, Heinrich SP, Farassat N, Marquez Neila P, Hug MJ, Albrecht P, Lagreze WA. Clinical Predictors in Acute Optic Neuritis: Analysis Based on Clinical Trial Data. Ophthalmology. 2025 Jun;132(6):631-643. doi: 10.1016/j.ophtha.2025.01.010. Epub 2025 Jan 17.

Reference Type DERIVED
PMID: 39827907 (View on PubMed)

Kuchlin S, Ihorst G, Heinrich SP, Marquez Neila P, Albrecht P, Hug MJ, Diem R, Lagreze WA. Disease Course of Clinically Isolated Optic Neuritis. Neurol Neuroimmunol Neuroinflamm. 2024 May;11(3):e200223. doi: 10.1212/NXI.0000000000200223. Epub 2024 Apr 8.

Reference Type DERIVED
PMID: 38588480 (View on PubMed)

Kuchlin S, Ihorst G, Grotejohann B, Beisse F, Heinrich SP, Albrecht P, Ungewiss J, Worner M, Hug MJ, Wolf S, Diem R, Lagreze WA; TONE Study Group. Treatment With Erythropoietin for Patients With Optic Neuritis: Long-term Follow-up. Neurol Neuroimmunol Neuroinflamm. 2023 Apr 24;10(4):e200067. doi: 10.1212/NXI.0000000000200067. Print 2023 Jul.

Reference Type DERIVED
PMID: 37094997 (View on PubMed)

Lagreze WA, Kuchlin S, Ihorst G, Grotejohann B, Beisse F, Volkmann M, Heinrich SP, Albrecht P, Ungewiss J, Worner M, Hug MJ, Wolf S, Diem R; TONE study group. Safety and efficacy of erythropoietin for the treatment of patients with optic neuritis (TONE): a randomised, double-blind, multicentre, placebo-controlled study. Lancet Neurol. 2021 Dec;20(12):991-1000. doi: 10.1016/S1474-4422(21)00322-7.

Reference Type DERIVED
PMID: 34800417 (View on PubMed)

Wilhelm H, Schabet M. The Diagnosis and Treatment of Optic Neuritis. Dtsch Arztebl Int. 2015 Sep 11;112(37):616-25; quiz 626. doi: 10.3238/arztebl.2015.0616.

Reference Type DERIVED
PMID: 26396053 (View on PubMed)

Lagreze W, Diem R. [New aspects in the therapy of multiple sclerosis and optic neuritis]. Ophthalmologe. 2014 Aug;111(8):709-14. doi: 10.1007/s00347-013-2987-7. German.

Reference Type DERIVED
PMID: 25063544 (View on PubMed)

Other Identifiers

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2013-002515-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DRKS00005298

Identifier Type: REGISTRY

Identifier Source: secondary_id

01KG1306

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

P000053

Identifier Type: -

Identifier Source: org_study_id

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