Safety and Efficacy Study of Erythropoietin as add-on Therapy of Methylprednisolone to Treat Acute Optic Neuritis

NCT ID: NCT00355095

Last Updated: 2012-09-13

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-08-31

Study Completion Date

2011-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The purpose of this study is to determine the safety and efficacy of erythropoietin as an add-on therapy to methylprednisolone in subjects with acute autoimmune optic neuritis.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

SUMMARY This study is a multicenter, double-blind, placebo-controlled, parallel-group study to determine the safety and efficacy of erythropoietin (Epo) as an add-on therapy to methylprednisolone (Mpred) in subjects with acute autoimmune optic neuritis.

The primary study endpoint is nerve fiber loss in the optical nerve head determined by optical coherence tomography at weeks 4, 8, and 16 compared to baseline.

Further study objectives include visual acuity, visual field perception, optic nerve atrophy determined by magnetic resonance imaging (MRI), and recovery of visual evoked potentials (VEPs).

A number of 40 subjects will be randomized in equal numbers into one of the two treatment groups.

Treatment groups:

Epo or placebo will be administered i.v. at three consecutive days. Epo or placebo is to be given once daily following application of Mpred preferably between 8 and 10 a.m..

Subjects will be randomized to one of the following two treatment groups and dosed as follows:

* Mpred at a dose of 1000 mg per day on days 1 - 3 given as an i.v. infusion AND 3.3 x 10\^4 IU recombinant human Epo per day on days 1- 3 given as an i.v. bolus injection.
* Mpred at a dose of 1000 mg per day on days 1 - 3 given as an i.v. infusion AND placebo (normal saline) on days 1 - 3 given as an i.v. bolus injection.

Men and women between the ages of 18 and 50, inclusive, diagnosed with acute unilateral optic neuritis with or without prior diagnosis of multiple sclerosis (according to McDonald criteria; Polman et al., 2005) will be considered for inclusion into the study. Those subjects must have a decreased visual acuity on the affected eye to 0.5 or less and must have signed written informed consent. While safety will be monitored during the study, an efficacy evaluation will be done after all subjects have completed week 16.

Each subject included in the study will be seen by a treating neurologist and an examining neurologist as well as by an examining ophthalmologist. The treating neurologist will function as the primary treating physician and conduct all subject safety assessments. The examining ophthalmologist and the examining neurologist will conduct all evaluations of vision/optical nerve head atrophy and neurological symptoms, respectively, but will not be involved in any other aspect of patient care. A neurophysiologist will perform measurements of VEPs. MRIs will be performed by a neuroradiologist.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Optic Neuritis

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

multiple sclerosis add-on Therapy erythropoietin methylprednisolone autoimmune optic neuritis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1

erythropoietin

Group Type ACTIVE_COMPARATOR

Erythropoietin

Intervention Type DRUG

intravenous daily 3.3 \*10\^4 Units, duration 3 days

2

Placebo

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Erythropoietin

intravenous daily 3.3 \*10\^4 Units, duration 3 days

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Erypo®

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

To be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of randomization:

* Must give written informed consent and authorize the release and use of protected health information (PHI).
* Must be 18 to 50 years old, inclusive, at the time of informed consent.
* Must have acute unilateral optic neuritis with or without prior diagnosis of MS (according to McDonald criteria).
* Symptoms related to optic neuritis must exist for no longer than 10 days prior to inclusion.
* Must have had normal visual acuity on both eyes before and no history of optic neuritis.
* Must have a decreased visual acuity on the affected eye to 0.5 or less at screening.

Exclusion Criteria

Medical history:

* Abnormal laboratory results or clinical signs indicative of any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neurological (other than MS), and/or other major disease.
* History of prior optic neuritis on the affected or non-affected eye.
* History of squint or amblyopia on either side.
* Hyperopia \> 3dptr on either side.
* Myopia \< -5dptr on either side.
* Astigmatism \> 2dptr on either side.
* Horizontal cup disc ratio \> 0.5 on either side.
* Retinal nerve fiber layer thickness outside normal values (with respect to the OCT data base).
* Ocular diseases effecting visual acuity or visual fields (cataract, glaucoma, maculadegeneration, diabetic retinopathy, retinal heredodegeneration or others).
* History of elevated blood pressure.
* Systolic blood pressure of \> 159 mmHg, diastolic blood pressure \> 99 mmHg at screening examination.
* History of thromboembolic events.
* Frequent thromboembolic events in 1st grade family members.
* Significant surgery within the 4 weeks prior to randomization.
* History of severe allergic or anaphylactic reactions after administration of Epo.
* History of malignancy.
* History of seizures.
* Tuberculosis with ongoing or unknown activity.
* Acute gastrointestinal ulceration within the last three months.
* Acute virus, bacterial or fungus infection.
* Infection with HIV, HBV, or HCV.
* History of colitis ulcerosa, diverticulitis, or acute enteroanastomosis.
* Severe osteoporosis.
* Active immunization within 2 weeks prior to inclusion.
* Diagnosis of phenylketonuria.
* Implanted cardiac pacemaker or other non MRI-compatible metallic body implants.
* History of drug or alcohol abuse (as defined by the investigator) within 2 years prior to randomization.
* Any of the following abnormal blood tests at screening: alanine transaminase/serum glutamate-pyruvate transaminase (AST/SGPT), or aspartate transaminase/serum glutamicoxaloacetic transaminase (AST/SGOT), gamma-glutamyl-transferase (GGT), or serum creatinine \> 2 times the upper limit of normal; hematocrit \> the upper limit of normal.

Treatment history

* Prior treatment with cyclosporine, mitoxantrone, methotrexate, cyclophosphamide or other immunosuppressive agents.
* Treatment with corticosteroids or Epo within 30 days prior to randomization. Miscellaneous
* Female subjects considering becoming pregnant while in the study.
* Female subjects who are currently pregnant or breast-feeding.
* Previous participation in this study or any other investigational drug study within the last four weeks.
* Current enrollment in any other investigational drug study.
* Unwillingness or inability to comply with the requirements of the protocol including the presence of any condition (physical, mental, or social) that is likely to affect the subject's ability to comply with the protocol.
* Any other reasons that, in the opinion of the investigator, the subject is determined to be unsuitable for enrollment in this study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Institut fuer anwendungsorientierte Forschung und klinische Studien gGmbH

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Ricarda Diem, MD Prof.

Role: STUDY_DIRECTOR

Department of Neurology University Homborg Hospital of the Saarland, Germany

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University Hospital of Hamburg-Eppendorf (Institut of Neuroimmunology and Clinical MS Research (INIMS))

Hamburg, City state of Hamburg, Germany

Site Status

Department of Neurology University Hospital Goettingen

Göttingen, Lower Saxony, Germany

Site Status

Department of Neurology University Homborg Hospital of the Saarland, Germany

Homburg, Saarland, Germany

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Germany

References

Explore related publications, articles, or registry entries linked to this study.

Maier K, Rau CR, Storch MK, Sattler MB, Demmer I, Weissert R, Taheri N, Kuhnert AV, Bahr M, Diem R. Ciliary neurotrophic factor protects retinal ganglion cells from secondary cell death during acute autoimmune optic neuritis in rats. Brain Pathol. 2004 Oct;14(4):378-87. doi: 10.1111/j.1750-3639.2004.tb00081.x.

Reference Type BACKGROUND
PMID: 15605985 (View on PubMed)

Suhs KW, Papanagiotou P, Hein K, Pul R, Scholz K, Heesen C, Diem R. Disease Activity and Conversion into Multiple Sclerosis after Optic Neuritis Is Treated with Erythropoietin. Int J Mol Sci. 2016 Sep 30;17(10):1666. doi: 10.3390/ijms17101666.

Reference Type DERIVED
PMID: 27706045 (View on PubMed)

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 DERIVED
PMID: 22926853 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

0026

Identifier Type: -

Identifier Source: org_study_id