Traumatic Optic NeuropathyPhase 1/2TONTTNCT01783847
Traumatic Optic Neuropathy Treatment Trial (TONTT)
A Phase 1/2 study testing Recombinant human erythropoietin (EPO), Observation and Methyl prednisolone in people with Traumatic Optic Neuropathy, run by Tehran University of Medical Sciences at 3 sites in Iran.
Trial 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… Read more about this study
- Who is it for?
- Ages 5 to 90 years
- Conditions the study is for
- Traumatic Optic Neuropathy
- What is being tested?
- Recombinant human erythropoietin (EPO), Observation and Methyl prednisolone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 3 sitesIran
- Study dates
- Feb 2015to Feb 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 90 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Having indirect traumatic optic neuropathy, not more than 3 weeks between trauma and treatment, normal fundoscopy
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Iran3 sites
Shiraz University of Medical Sciences
Shiraz, Fars
Iran University of Medical Sciences
Tehran, 1467744814
Beheshti University of Medical Sciences
Tehran
About this study
Official title: 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.
- Conditions
- Traumatic Optic Neuropathy
- Being tested
- Recombinant human erythropoietin (EPO), Observation, Methyl prednisolone
- Keywords
- Erythropoietin, Traumatic Optic Neuropathy, Visual function
- Medical subject headings
- Optic Nerve Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant human erythropoietin (EPO)Drug
Also called EPO (Pooyesh darou Co., Tehran)
4000 units per vial
ObservationOther
Just observation
Methyl prednisoloneDrug
Also called Depo-Medrol
250 mg every 6 hours for 3 days.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Recombinant human erythropoietin (EPO) |
| Methylprednisolone | Active comparator | Just Intravenous Methyl prednisolone 250 mg every 6 hours for 3 days. Receives: Drug: Methyl prednisolone |
| Observation | Other | Observation Receives: Other: Observation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline at least 3 months after treatment
Secondary outcomes (1)
Number of Participants With Relative Afferent Papillary Defect (RAPD) Grade +4
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
Measured: Change from baseline at least 3 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2013 (estimated)
- Study startFeb 2015
- Primary completionApr 2016
- Study completionFeb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Traumatic Optic NeuropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Care provider
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tehran University of Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Iran University of Medical Sciences, Mashhad University of Medical Sciences, Shahid Beheshti University of Medical Sciences
- Responsible party
- Sponsor
- Investigators
- Mohsen B Kashkouli, MD, Study chair, Iran University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01783847
- Sponsor's protocol ID
- 90-01-124-12972
- Acronym
- TONTT
- Status last verified
- Apr 2016
- First submitted
- 1 Feb 2013
- Last updated
- 7 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Visual Recovery After Erythropoietin (EPO) Injection, in Patients With Traumatic Optic Neuropathy (TON)
- ClinicalTrials.gov ID
- NCT01783847
- Acronym / sponsor ID
- TONTT / 90-01-124-12972
- Conditions
- Traumatic Optic Neuropathy
- Keywords
- Erythropoietin, Traumatic Optic Neuropathy, Visual function
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- Tehran University of Medical SciencesUniversity, hospital or other
- Collaborators
- Iran University of Medical Sciences, Mashhad University of Medical Sciences, Shahid Beheshti University of Medical Sciences
- Study start
- Feb 2015
- Primary completion
- Apr 2016 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 5 Feb 2013 (estimated)
- Results
- Posted 12 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Recombinant human erythropoietin (EPO) | Experimental | Drug: 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 |
| Methylprednisolone | Active comparator | Drug: Methyl prednisoloneJust Intravenous Methyl prednisolone 250 mg every 6 hours for 3 days. |
| Observation | Other | Other: ObservationObservation |
Who may qualify
- Ages
- 5 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Having indirect traumatic optic neuropathy, not more than 3 weeks between trauma and treatment, normal fundoscopy
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant human erythropoietin (EPO)Also: EPO (Pooyesh darou Co., Tehran)4000 units per vial | Drug | Recombinant human erythropoietin (EPO) |
| ObservationJust observation | Other | Observation |
| Methyl prednisoloneAlso: Depo-Medrol250 mg every 6 hours for 3 days. | Drug | Methylprednisolone |
Primary outcome
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.
1 secondary outcome
Number of Participants With Relative Afferent Papillary Defect (RAPD) Grade +4
Time frame: Change from baseline at least 3 months after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohsen B Kashkouli, MD study chair
Iran University of Medical Sciences
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Recombinant human erythropoietin (EPO), Observation and Methyl prednisolone in people with Traumatic Optic Neuropathy, run by Tehran University of Medical Sciences at 3 sites in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Change/Improvement Visual Acuity From the Beseline (time frame: Change from baseline at least 3 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2019.