Optic NeuritisPhase 2NCT00355095
Safety and Efficacy Study of Erythropoietin as add-on Therapy of Methylprednisolone to Treat Acute Optic Neuritis
A Phase 2 study testing Erythropoietin in people with Optic Neuritis, run by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH at 3 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Optic Neuritis
- What is being tested?
- Erythropoietin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesGermany
- Study dates
- Aug 2006to Jul 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 39Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
Department of Neurology University Hospital Goettingen
Göttingen, Lower Saxony, 37075
University Hospital of Hamburg-Eppendorf (Institut of Neuroimmunology and Clinical MS Research (INIMS))
Hamburg, Free and Hanseatic City of Hamburg, 20246
Department of Neurology University Homborg Hospital of the Saarland, Germany
Homburg, Saarland, 66421
About this study
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)
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.
Read the 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.
- Conditions
- Optic Neuritis
- Being tested
- Erythropoietin
- Keywords
- multiple sclerosis, add-on Therapy, erythropoietin, methylprednisolone, autoimmune optic neuritis
- Medical subject headings
- Optic Neuritis, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErythropoietinDrug
Also called Erypo®
intravenous daily 3.3 *10^4 Units, duration 3 days
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | erythropoietin Receives: Drug: Erythropoietin |
| 2 | No intervention | Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 months
Secondary outcomes (1)
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)
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2006 (estimated)
- Study startAug 2006
- Primary completionFeb 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Optic NeuritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
- Sponsor type
- University, hospital or other
- Investigators
- Ricarda Diem, MD Prof., Study director, Department of Neurology University Homborg Hospital of the Saarland, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00355095
- Sponsor's protocol ID
- 0026
- Status last verified
- Sep 2012
- First submitted
- 20 Jul 2006
- Last updated
- 13 Sep 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 15605985Suhs 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.
PubMed 27706045Suhs 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.
PubMed 22926853
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00355095
- Acronym / sponsor ID
- 0026
- Conditions
- Optic Neuritis
- Keywords
- multiple sclerosis, add-on Therapy, erythropoietin, methylprednisolone, autoimmune optic neuritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Institut fuer anwendungsorientierte Forschung und klinische Studien GmbHUniversity, hospital or other
- Study start
- Aug 2006
- Primary completion
- Feb 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 21 Jul 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Erythropoietinerythropoietin |
| 2 | No intervention | –Placebo |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (39 listed)
- Candidates will be excluded from study if any of the following exclusion criteria exist at the time of randomization:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErythropoietinAlso: Erypo®intravenous daily 3.3 *10^4 Units, duration 3 days | Drug | 1 |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2012.
- Background: PubMed 15605985Maier 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.
- Derived from this study: PubMed 27706045Suhs 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.
- Derived from this study: PubMed 22926853Suhs 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ricarda Diem, MD Prof. study director
Department of Neurology University Homborg Hospital of the Saarland, Germany
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Erythropoietin in people with Optic Neuritis, run by Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH at 3 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00355095, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2012.