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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00355095
Recruitment Status : Completed
First Posted : July 21, 2006
Last Update Posted : September 13, 2012
Sponsor:
Information provided by:
Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH

Tracking Information
First Submitted Date  ICMJE July 20, 2006
First Posted Date  ICMJE July 21, 2006
Last Update Posted Date September 13, 2012
Study Start Date  ICMJE August 2006
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2009)
nerve fiber loss in the optical nerve head determined by optical coherence tomography at weeks 4,8 and 16 compared to baseline. Measurements at baseline and week 16 are used to calculate estimates for changes and differences between the groups. [ Time Frame: 4 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 20, 2006)
  • The safety and tolerability of Epo in combination with Mpred in subjects with optic
  • neuritis/MS is a primary interest of this study. Additionally, an objective of primary interest is
  • to calculate an estimate for the efficacy of this therapy with respect to nerve fiber loss in the
  • optical nerve head after an episode of acute optic neuritis. Nerve fiber loss will be measured
  • by OCT using the change in retinal nerve fiber layer thickness around the optical nerve head
  • and the change of neural tissue volume in the optical nerve head itself. The measurements will
  • be performed at baseline, week 4, week 8, and week 16. The measurements at baseline and
  • week 16 are used to calculate estimates for changes and differences between the groups.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2009)
Visual acuity and visual field perception determined at weeks 1, 4, 8, 16 compared to baseline (week 0). MRI measurements of optic nerve atrophy performed at weeks 4, 8 and 16 compared to baseline (week 0) [ Time Frame: 4 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2006)
  • Secondary objectives include:
  • Visual acuity determined at weeks 1, 4, 8, and 16 compared to baseline (week 0).
  • Visual field perception determined by automated perimetry at weeks 1, 4, 8, and 16
  • compared to baseline (week 0)
  • Optic nerve atrophy assessed by volumetric MRI data as well as magnetization
  • transfer and/or Diffusion Tensor Imaging (DTI). MRI measurements will be
  • performed at weeks 4, 8, and 16 and will be compared to baseline (week 0).
  • Recovery of latency and amplitude of visual evoked potentials (VEPs).
  • Electrophysiological measurements will be performed at weeks 4, 8, and 16, and will
  • be compared to baseline (week 0).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Erythropoietin as add-on Therapy of Methylprednisolone to Treat Acute Optic Neuritis
Official Title  ICMJE Double Blind, Placebo-controlled Study to Determine the Safety and Efficacy of Erythropoietin as an add-on Therapy of Methylprednisolone in Subjects With Acute Optic Neuritis (VISION PROTECT)
Brief Summary 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

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Optic Neuritis
Intervention  ICMJE Drug: Erythropoietin
intravenous daily 3.3 *10^4 Units, duration 3 days
Other Name: Erypo®
Study Arms  ICMJE
  • Active Comparator: 1
    erythropoietin
    Intervention: Drug: Erythropoietin
  • No Intervention: 2
    Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 20, 2006)
40
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2011
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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:

Candidates will be excluded from study if any of the following exclusion criteria exist at the time of randomization:

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00355095
Other Study ID Numbers  ICMJE 0026
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dirk Simon, Institut fuer anwendungsorientierte Forschung und klinische Studien gGmbH
Study Sponsor  ICMJE Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ricarda Diem, MD Prof. Department of Neurology University Homborg Hospital of the Saarland, Germany
PRS Account Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
Verification Date September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP