Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT01962571
Recruitment Status : Active, not recruiting
First Posted : October 14, 2013
Last Update Posted : March 6, 2019
Sponsor:
Collaborator:
German Federal Ministry of Education and Research
Information provided by (Responsible Party):
Prof. Dr. Wolf Lagrèze, University Eye Hospital, Freiburg

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Optic Neuritis Drug: Erythropoietin alfa Drug: Placebo Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Optic Neuritis With Erythropoietin: a Randomised, Double-blind, Placebo-controlled Trial
Actual Study Start Date : November 2014
Estimated Primary Completion Date : March 31, 2019
Estimated Study Completion Date : May 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Erythropoietin alfa
Placebo Comparator: 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.
Drug: Placebo
Other Name: Saline




Primary Outcome Measures :
  1. Global retinal nerve fibre layer thickness (RNFLT-G) [ Time Frame: 6 months ]
    Determination of the efficacy of erythropoietin compared to placebo given as add-on to methylprednisolone (standard of care) as assessed by measurement of global retinal nerve fibre layer thickness (RNFLT-G) in the affected eye 6 months after randomisation.

  2. Low contrast visual acuity (LCVA) [ Time Frame: 6 months ]
    Determination of the efficacy of erythropoietin compared to placebo given as add-on to methylprednisolone (standard of care) as assessed by measurement of low contrast visual acuity (LCVA) in the affected eye 6 months after randomisation.


Secondary Outcome Measures :
  1. Absolute values of the global retinal nerve fibre layer thickness [ Time Frame: 6 months ]
  2. Retinal nerve fibre layer thickness in the papillomacular bundle [ Time Frame: 6 months ]
  3. Retinal nerve fibre layer thickness in the temporal quadrant [ Time Frame: 6 months ]
  4. Total macular volume [ Time Frame: 6 months ]
  5. Visual acuity [ Time Frame: 6 months ]
  6. Contrast sensitivity [ Time Frame: 6 months ]
  7. Mean visual field defect [ Time Frame: 6 months ]
  8. Latency [ms] and amplitude [µV] of visual evoked potentials (VEP) [ Time Frame: 6 months ]
  9. Expanded Disability Status Scale (EDSS) score [ Time Frame: 6 months ]
  10. Quality of life [ Time Frame: 6 months ]
    Determined by NEI-VFQ-25

  11. Safety [ Time Frame: Screening until end of study ]
    Assessment of AEs / SAEs



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Patients eligible for inclusion in this trial must meet all of the following 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01962571


Locations
Layout table for location information
Germany
Medical Center - University of Freiburg, Eye Hospital
Freiburg, Baden-Wuerttemberg, Germany, 79106
Heidelberg University Hospital, Department of Neurooncology
Heidelberg, Baden-Wuerttemberg, Germany, 69120
Tuebingen University Hospital
Tuebingen, Baden-Wuerttemberg, Germany, 72076
University Hospital Erlangen
Erlangen, Bayern, Germany, 91054
University Hospital of Munich
Munich, Bayern, Germany, 81377
University Hospital Klinikum rechts der Isar, Munich
Munich, Bayern, Germany, 81675
University Medical Center Goettingen
Goettingen, Niedersachen, Germany, 37075
Hannover Medical School
Hannover, Niedersachsen, Germany, 30625
Duesseldorf University Hospital
Duesseldorf, Nordrhein-Westfalen, Germany, 40225
University Medical Center of the Johannes Gutenberg University Mainz
Mainz, Rheinland-Pfalz, Germany, 55131
University Medical Center Hamburg-Eppendorf
Hamburg, Germany, 20246
Sponsors and Collaborators
University Eye Hospital, Freiburg
German Federal Ministry of Education and Research
Investigators
Layout table for investigator information
Principal Investigator: Wolf A. Lagrèze, Prof. Eye Hospital, Medical Center - University of Freiburg

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Prof. Dr. Wolf Lagrèze, Prof. Dr. med., University Eye Hospital, Freiburg
ClinicalTrials.gov Identifier: NCT01962571     History of Changes
Other Study ID Numbers: P000053
2013-002515-10 ( EudraCT Number )
DRKS00005298 ( Registry Identifier: German Clinical Trials Register (DRKS) )
01KG1306 ( Other Grant/Funding Number: Federal Ministry of Education and Research )
First Posted: October 14, 2013    Key Record Dates
Last Update Posted: March 6, 2019
Last Verified: March 2019

Keywords provided by Prof. Dr. Wolf Lagrèze, University Eye Hospital, Freiburg:
Optic neuritis
Multiple Sclerosis
Clinically isolated syndrome
Erythropoietin

Additional relevant MeSH terms:
Layout table for MeSH terms
Neuritis
Optic Neuritis
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Optic Nerve Diseases
Cranial Nerve Diseases
Eye Diseases
Epoetin Alfa
Hematinics