Traumatic Optic Neuropathy Treatment Trial (TONTT) (TONTT)

April 24, 2019 updated by: Tehran University of Medical Sciences

Study of Visual Recovery After Erythropoietin (EPO) Injection, in Patients With Traumatic Optic Neuropathy (TON)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

117

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Iran, Islamic Republic of
      • Tehran, Iran, Islamic Republic of, 1467744814
        • Iran University of Medical Sciences
      • Tehran, Iran, Islamic Republic of
        • Beheshti University of Medical Sciences
    • Fars
      • Shiraz, Fars, Iran, Islamic Republic of
        • shiraz University of medical sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 88 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Observation
Other: Observation
Just observation
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 Names:
  • 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 Names:
  • Depo-Medrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Change from baseline at least 3 months after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Change from baseline at least 3 months after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tehran University of Medical Sciences

Collaborators

Shahid Beheshti University of Medical Sciences
Mashhad University of Medical Sciences
Iran University of Medical Sciences

Investigators

  • Study Chair: Mohsen B Kashkouli, MD, Iran University of Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2015

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

February 1, 2017

Study Registration Dates

First Submitted

February 1, 2013

First Submitted That Met QC Criteria

February 4, 2013

First Posted (Estimate)

February 5, 2013

Study Record Updates

Last Update Posted (Actual)

May 7, 2019

Last Update Submitted That Met QC Criteria

April 24, 2019

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 90-01-124-12972

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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