Traumatic Optic Neuropathy Treatment Trial (TONTT)

NCT01783847 | Completed Phase 1 Results DMC

• 1 other identifier: 90-01-124-12972
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 3

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.

Conditions

Traumatic Optic Neuropathy

Keywords

Erythropoietin; Traumatic Optic Neuropathy; Visual function

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Change/Improvement Visual Acuity From the Beseline

  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 Outcomes (1)

• Number of Participants With Relative Afferent Papillary Defect (RAPD) Grade +4

  Change from baseline at least 3 months after treatment

Study Arms (3)

Recombinant human erythropoietin (EPO)

EXPERIMENTAL

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)

Methylprednisolone

ACTIVE COMPARATOR

Just Intravenous Methyl prednisolone 250 mg every 6 hours for 3 days.

Drug: Methyl prednisolone

Observation

OTHER

Observation

Other: Observation

Interventions

Recombinant human erythropoietin (EPO) DRUG

4000 units per vial

Also known as: EPO (Pooyesh darou Co., Tehran)

Recombinant human erythropoietin (EPO)

Observation OTHER

Just observation

Observation

Methyl prednisolone DRUG

250 mg every 6 hours for 3 days.

Also known as: Depo-Medrol

Methylprednisolone

Eligibility Criteria

• Age: 5 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tehran University of Medical Sciences: lead
• Iran University of Medical Sciences: collaborator
• Mashhad University of Medical Sciences: collaborator
• Shahid Beheshti University of Medical Sciences: collaborator

Study Sites (3)

Shiraz University of Medical Sciences

Shiraz, Fars, Iran

Location

Iran University of Medical Sciences

Tehran, 1467744814, Iran

Location

Beheshti University of Medical Sciences

Tehran, Iran

Location

MeSH Terms

Conditions

Optic Nerve Injuries

Interventions

Observation; Methylprednisolone Acetate

Condition Hierarchy (Ancestors)

Cranial Nerve Injuries; Cranial Nerve Diseases; Nervous System Diseases; Optic Nerve Diseases; Craniocerebral Trauma; Trauma, Nervous System; Eye Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques; Methylprednisolone; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Mohsen Bahmani Kashkouli
• Organization: Iran university of Medical Sciences

mkashkouli2@gmail.com

00989121777003

Study Officials

• Mohsen B Kashkouli, MD

  Iran University of Medical Sciences

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2013
• First Posted: February 5, 2013
• Study Start: February 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: February 1, 2017
• Last Updated: May 7, 2019
• Results First Posted: September 12, 2018

Record last verified: 2016-04

Locations

IR (3)