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

This study has been completed.
Sponsor:
Information provided by:
Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
ClinicalTrials.gov Identifier:
NCT00355095
First received: July 20, 2006
Last updated: September 12, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Optic Neuritis
Drug: Erythropoietin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: August 2006
Study Completion Date: July 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
erythropoietin
Drug: Erythropoietin
intravenous daily 3.3 *10^4 Units, duration 3 days
Other Name: Erypo®
No Intervention: 2
Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00355095

Locations
Germany
Department of Neurology University Hospital Goettingen
Goettingen, Niedersachsen, Germany, 37075
Department of Neurology University Homborg Hospital of the Saarland, Germany
Homburg, Saarland, Germany, 66421
University Hospital of Hamburg-Eppendorf (Institut of Neuroimmunology and Clinical MS Research (INIMS))
Hamburg, Germany, 20246
Sponsors and Collaborators
Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
Investigators
Study Director: Ricarda Diem, MD Prof. Department of Neurology University Homborg Hospital of the Saarland, Germany
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dirk Simon, Institut fuer anwendungsorientierte Forschung und klinische Studien gGmbH
ClinicalTrials.gov Identifier: NCT00355095     History of Changes
Other Study ID Numbers: 0026
Study First Received: July 20, 2006
Last Updated: September 12, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH:
multiple sclerosis
add-on Therapy
erythropoietin
methylprednisolone
autoimmune optic neuritis

Additional relevant MeSH terms:
Neuritis
Optic Neuritis
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Optic Nerve Diseases
Cranial Nerve Diseases
Eye Diseases
Epoetin alfa
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 30, 2014