Traumatic Optic Neuropathy Treatment Trial (TONTT)

NCT ID: NCT01783847

Last Updated: 2019-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 117 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2017-02-28

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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

Group Type: EXPERIMENTAL

Recombinant human erythropoietin (EPO)

Intervention Type: DRUG

4000 units per vial

Methylprednisolone

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

Group Type: ACTIVE_COMPARATOR

Methyl prednisolone

Intervention Type: DRUG

250 mg every 6 hours for 3 days.

Observation

Observation

Group Type: OTHER

Observation

Intervention Type: OTHER

Just observation

Interventions

Recombinant human erythropoietin (EPO)

4000 units per vial

Intervention Type: DRUG

Observation

Just observation

Intervention Type: OTHER

Methyl prednisolone

250 mg every 6 hours for 3 days.

Intervention Type: DRUG

Other Intervention Names

EPO (Pooyesh darou Co., Tehran); Depo-Medrol

Eligibility 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

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iran University of Medical Sciences

OTHER

Sponsor Role: collaborator

Mashhad University of Medical Sciences

OTHER

Sponsor Role: collaborator

Shahid Beheshti University of Medical Sciences

OTHER

Sponsor Role: collaborator

Tehran University of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mohsen B Kashkouli, MD

Role: STUDY_CHAIR

Iran University of Medical Sciences

Locations

Shiraz University of Medical Sciences

Shiraz, Fars, Iran

Iran University of Medical Sciences

Tehran, , Iran

Beheshti University of Medical Sciences

Tehran, , Iran

Countries

Iran

Other Identifiers

90-01-124-12972

Identifier Type: -

Identifier Source: org_study_id