Traumatic Optic Neuropathy Treatment Trial (TONTT)
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. 20 The aim of this study is to compare the effectiveness of EPO with steroid and observation in TON in a Multi- center randomized clinical trial.
Traumatic Optic Neuropathy
Drug: Recombinant human erythropoietin (EPO)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
|Official Title:||Study of Visual Recovery After Erythropoietin (EPO) Injection, Steroid Injection or Observation in Patients With Traumatic Optic Neuropathy (TON)|
- Visual function [ Time Frame: change from baseline until 3 months after treatment ] [ Designated as safety issue: No ]Visual Acuity, Relative Afferent Pupillary Defect, and Color vision 1,2,3 days, 1 week, 2 weeks and 1,3 months after treatment
- Visual Field [ Time Frame: Change from baseline 3 months after treatment ] [ Designated as safety issue: No ]Since visual acuity might be too low to allow testing visual field, it will be performed if the visual acuity is good enough for such a test.
|Study Start Date:||February 2011|
|Estimated Study Completion Date:||April 2016|
|Estimated Primary Completion Date:||February 2016 (Final data collection date for primary outcome measure)|
Experimental: Recombinant human erythropoietin (EPO)
20,000 unit per day of EPO, Intravenous infusion for three sequential days.
Drug: Recombinant human erythropoietin (EPO)
4000 units per vial
Other Name: EPO (Pooyesh darou Co., Tehran)
Active Comparator: Methylprednisolone hemisuccinate
1 gram per day of Intravenous injection of methylprednisolone for 3 days. If vision improved, it will be followed by oral steroid 1mg/kg/day for 11 days.
500 mg per vial
Other Name: Methylprednisolone hemi succinate (Mylan, France)
No Intervention: Observation
No any treatment will be given.
|Iran, Islamic Republic of|
|Tehran University of Medical Sciences||Recruiting|
|Tehran, Iran, Islamic Republic of|
|Contact: Mohsen B Kashkouli, MD firstname.lastname@example.org|
|Principal Investigator: Farzad Pakdel, MD|
|Principal Investigator: Mohammad Etezad Razavi, MD|
|Principal Investigator: Morteza Entezari, MD|
|Sub-Investigator: Marzieh Nojomi, MD|
|Study Director:||Mohsen B Kashkouli, MD||Tehran University of Medical Sciences|