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Traumatic Optic Neuropathy Treatment Trial (TONTT) (TONTT)

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: NCT01783847
Recruitment Status : Completed
First Posted : February 5, 2013
Results First Posted : September 12, 2018
Last Update Posted : May 7, 2019
Sponsor:
Collaborators:
Iran University of Medical Sciences
Mashhad University of Medical Sciences
Shahid Beheshti University of Medical Sciences
Information provided by (Responsible Party):
Tehran University of Medical Sciences

Brief Summary:
The pathophysiology of Traumatic Optic Neuropathy (TON) is thought to be multifactorial, and some researchers have also postulated a primary and secondary mechanism of injury.TON is categorized as direct or indirect.In indirect TON cases, the injury to the axons is thought to be induced by shearing forces that are transmitted to the fibers or to the vascular supply of the nerve. Studies have shown that forces applied to the frontal bone and malar eminences are transferred and concentrated in the area near the optic canal. The tight adherence of the optic nerve's dural sheath to the periosteum within the optic canal is also thought to contribute to this segment of the nerve being extremely susceptible to the deformative stresses of the skull bones. Such injury leads to ischemic injury to the axons of the retinal ganglion cells within the optic canal. At present, no studies validate a particular approach to the management of TON. There are three management lines for these patients that include 1)observation only;2)medical treatment with high or megadoses of methylprednisolone; and 3)surgical intervention. Generally no line precedes the others and additionally, medical or surgical interventions may result in serious side effects or complications. In 2005, the results of the Corticosteroid Randomization after Significant Head Injury (CRASH) trial raised concerns regarding the use of mega dose steroids in traumatic brain injury. This study was the largest randomized study that evaluated steroids in patients with traumatic brain injury and was stopped early due to the significantly increased risk of death in patients that received mega dose steroids at their 6-month follow-up when compared with the placebo group (25.7% vs 22.3%; Relative Risk 1.15 Confidence Interval 1.07 to 1.24; p=0.0001). Although the etiology of the increased risk of death was not determined, the findings of this study should be taken into consideration when managing cases of TON with concurrent traumatic brain injury. Very recently it has been shown the cytokine hormone erythropoietin (EPO) that had been long known and used as a valuable agent to promote hematopoiesis has been protective in experimental models of mechanical trauma, neuroinflammation, cerebral and retinal ischemia, and even in a human stroke trial, and most notably in optic nerve transection. A double blind placebo-controlled multicenter trial on EPO add-on treatment in chronic schizophrenic men was performed. Treatment over 12 weeks with high-dose weekly (40,000 IU intravenously) EPO led to significant improvement of cognitive performance compared to placebo controls. Different studies have been performed on the effect of EPO on neuropathy in different studies. The investigators recently published our results on treating patients with TON with EPO and found it safe and effective. Patients were compared with a historical control group of patients who received no treatment for TON. A better visual recovery was found. The aim of this study is to determine the effectiveness of EPO on TON in a Multi- center clinical trial using a semi-experimental design.

Condition or disease Intervention/treatment Phase
Traumatic Optic Neuropathy Drug: Recombinant human erythropoietin (EPO) Other: Observation Drug: Methyl prednisolone Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 117 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Care Provider)
Primary Purpose: Treatment
Official Title: Study of Visual Recovery After Erythropoietin (EPO) Injection, in Patients With Traumatic Optic Neuropathy (TON)
Study Start Date : February 2015
Actual Primary Completion Date : April 2016
Actual Study Completion Date : February 2017


Arm Intervention/treatment
Experimental: Recombinant human erythropoietin (EPO)
Intravenous EPO 10,000 IU for 5-13 years of age and 20,000 IU for >13 years/ day for 3 days
Drug: Recombinant human erythropoietin (EPO)
4000 units per vial
Other Name: EPO (Pooyesh darou Co., Tehran)

Active Comparator: Methylprednisolone
Just Intravenous Methyl prednisolone 250 mg every 6 hours for 3 days.
Drug: Methyl prednisolone
250 mg every 6 hours for 3 days.
Other Name: Depo-Medrol

Observation
Observation
Other: Observation
Just observation




Primary Outcome Measures :
  1. Number of Participants With Change/Improvement Visual Acuity From the Beseline [ Time Frame: Change from baseline at least 3 months after treatment ]
    Best corrected visual acuity will measure at 1,2,3 days, 1 week, 2 weeks and 1 month and at least 3 months after treatment. Improvement is defined based on 1) mean logMAR[12], 2) 0.3 change in logMAR (improvement, deterioration, and no change) [12,16] , 3) mean improvement percentage which is calculated as: improvement%= (logMar ( of VA after treatment)-logMar ( of initial VA))/(logMar(20/13)˟-logMar ( of initial VA) 4) percentage of patients at different ordinal categorization of the BCVA as no light perception (NLP), light perception (LP)and hand motion (HM), count fingers (CF), and ≥ 20/200.


Secondary Outcome Measures :
  1. Number of Participants With Relative Afferent Papillary Defect (RAPD) Grade +4 [ Time Frame: Change from baseline at least 3 months after treatment ]
    A positive RAPD means there are differences between the two eyes in the afferent pathway due to retinal or optic nerve disease. Graded from +1 to +4. The higher one is a better grade



Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 90 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Having indirect traumatic optic neuropathy, not more than 3 weeks between trauma and treatment, normal fundoscopy

Exclusion Criteria:

  • Having other injuries that effect on visual function, direct optic neuropathy, glaucoma, diabetic retinopathy, uncontrolled hypertension, polycythemia, creatinin more than 3 mg/dl, sensitivity to EPO, hyperkalemia, women who use contraceptive pill, pregnant and breast feeding women, history of stroke and cardiovascular diseases, having malignancy

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): NCT01783847


Locations
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Iran, Islamic Republic of
Shiraz University of Medical Sciences
Shiraz, Fars, Iran, Islamic Republic of
Iran University of Medical Sciences
Tehran, Iran, Islamic Republic of, 1467744814
Beheshti University of Medical Sciences
Tehran, Iran, Islamic Republic of
Sponsors and Collaborators
Tehran University of Medical Sciences
Iran University of Medical Sciences
Mashhad University of Medical Sciences
Shahid Beheshti University of Medical Sciences
Investigators
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Study Chair: Mohsen B Kashkouli, MD Iran University of Medical Sciences

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Responsible Party: Tehran University of Medical Sciences
ClinicalTrials.gov Identifier: NCT01783847    
Other Study ID Numbers: 90-01-124-12972
First Posted: February 5, 2013    Key Record Dates
Results First Posted: September 12, 2018
Last Update Posted: May 7, 2019
Last Verified: April 2016
Keywords provided by Tehran University of Medical Sciences:
Erythropoietin
Traumatic Optic Neuropathy
Visual function
Additional relevant MeSH terms:
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Peripheral Nervous System Diseases
Optic Nerve Diseases
Optic Nerve Injuries
Neuromuscular Diseases
Nervous System Diseases
Cranial Nerve Diseases
Eye Diseases
Cranial Nerve Injuries
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Epoetin Alfa
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents