Therapy of Toxic Optic Neuropathy Via Combination of Stem Cells With Electromagnetic Stimulation

NCT04877067 | Completed Phase 3 DMC

• 1 other identifier: 56733164/203 E.1925
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

The axons of the retinal ganglion cells combine to form the optic nerve. The optic nerve transmits electrical signals to the visual cortex by various synapses. Optic nerve axons are more sensitive to toxins than retina because they are outside the blood retinal barrier. Methanol, various solvents and heavy metals, carbon dioxide, antiarrhythmic, antiepileptic, antibiotics and some vasoactive drugs can cause toxic optic neuropathy. There is a different pathophysiology for each toxin. Methanol is easily accessible alcohol in all types of disinfectants. Methanol is converted into formaldehyde and formic acid while metabolized in the liver. Formaldehyde disrupts ATP synthesis by blocking mitochondrial function and oxidative phosphorylation. Formic acid causes demyelination as a result of metabolic acidosis. Neuroinflammation occurs when denatured proteins block axoplasmic flow. All these processes can lead to apoptosis and permanent vision loss. Sildenafil is a vasoactive drug used in erectile dysfunction. Sildenafil decreases optic nerve head blood flow. Neuroinflammation develops secondary to the cessation of axoplasmic flow after hypoxia. If hypoxia and neuroinflammatiom persists, apoptosis and permanent vision loss develop. Amiodarone is an ion channel blocker used in the treatment of cardiac arrhythmias. Long-term use may cause disruption of ion channel balance in the optic nerve. This condition leads to asymmetric neuroinflammation and apoptosis. Wharton's jelly derived mesenchymal stem cells (WJ-MSC) can increase mitochondrial ATP synthesis with paracrine effects and suppress neuroinflammation with immunomodulatory effects. Repetitive electromagnetic stimulation (rEMS) can rearrange ion channel balances and axoplasmic flow. The aim of this prospective phase-3 clinical study is to investigate the effect of WJ-MSC and rEMS combination in the therapy of toxic optic neuropathies. This combination is the first study in the literature for the therapy of toxic optic neuropathies.

Conditions

Methanol Poisoning; Toxic Optic Neuropathy; Stem Cell Tyrosine Kinase 1 Y842X; Magnetic Field Exposure

Keywords

Toxic optic neuropathy; Wharton's jelly derived mesenchymal stem cell; Repetitive electromagnetic stimulation

Outcome Measures

Primary Outcomes (1)

• ETDRS visual acuity:

  The visual acuity scores obtained from the T0 and T2 examinations were analyzed and compared using statistical tests to determine effectiveness.

  Change from baseline BCVA at 3 months

Secondary Outcomes (3)

• Visual field sensitivity: Fundus perimetry deviation index (FPDI, %)

  Change from baseline FPDI at 3 months

• Ganglion cell complex thickness (GCC thickness, µm):

  Change from baseline GCC thickness at 3 months

• Pattern visual evoked potential (pVEP)

  Change from baseline p100 latency and amolitude at 3 months

Study Arms (3)

WJ-MSC combine witf rEMS

ACTIVE COMPARATOR

WJ-MSC was applied first to the patients after necessary preparations. rEMS application was started 10 days after WJ-MSC application.

Biological: Wharton jelly derived mesenchymal stem cell; Device: Repetitive electromagnetic stimulation

Only rEMS

ACTIVE COMPARATOR

rEMS applications were repeated 10 times with a 1-week interval.

Device: Repetitive electromagnetic stimulation

Only WJ-MSC

ACTIVE COMPARATOR

WJ-MSC was applied only one time for both eyes.

Biological: Wharton jelly derived mesenchymal stem cell

Interventions

Wharton jelly derived mesenchymal stem cell BIOLOGICAL

WJ-MSC

Also known as: CordoSight

Only WJ-MSC; WJ-MSC combine witf rEMS

Repetitive electromagnetic stimulation DEVICE

rEMS

Also known as: Magnovision

Only rEMS; WJ-MSC combine witf rEMS

Eligibility Criteria

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

You may qualify if:

• Cases poisoned with a toxic agent within 3 months
• Patients with BCVA better than 35 letters
• Any degree of visual field loss
• Patients over 18 years old

You may not qualify if:

• Cases poisoned with a toxic agent more than 3 months
• Patients with BCVA less than 35 letters: to perform the visual field test correctly
• Neurological sequelae that cannot be cooperated
• Smoking

Sponsors & Collaborators

• Ankara Universitesi Teknokent: lead
• International Olympic Committee: collaborator

Study Sites (2)

Ankara University Biotechnology Institute

Ankara, Türkiye, 06312, Turkey (Türkiye)

Location

Umut Arslan

Ankara, 06000, Turkey (Türkiye)

Location

Related Publications (6)

• Ozmert E, Arslan U. Management of retinitis pigmentosa by Wharton's jelly derived mesenchymal stem cells: preliminary clinical results. Stem Cell Res Ther. 2020 Jan 13;11(1):25. doi: 10.1186/s13287-020-1549-6.

  PMID: 31931872 BACKGROUND

• Ozmert E, Arslan U. Management of retinitis pigmentosa by Wharton's jelly-derived mesenchymal stem cells: prospective analysis of 1-year results. Stem Cell Res Ther. 2020 Aug 12;11(1):353. doi: 10.1186/s13287-020-01870-w.

  PMID: 32787913 BACKGROUND

• Arslan U, Ozmert E. Treatment of resistant chronic central serous chorioretinopathy via platelet-rich plasma with electromagnetic stimulation. Regen Med. 2020 Aug;15(8):2001-2014. doi: 10.2217/rme-2020-0056. Epub 2020 Oct 27.

  PMID: 33107400 BACKGROUND

• Ozmert E, Arslan U. Management of Deep Retinal Capillary Ischemia by Electromagnetic Stimulation and Platelet-Rich Plasma: Preliminary Clinical Results. Adv Ther. 2019 Sep;36(9):2273-2286. doi: 10.1007/s12325-019-01040-2. Epub 2019 Aug 5.

  PMID: 31385285 BACKGROUND

• Arslan U, Ozmert E. Management of Retinitis Pigmentosa via Platelet-Rich Plasma or Combination with Electromagnetic Stimulation: Retrospective Analysis of 1-Year Results. Adv Ther. 2020 May;37(5):2390-2412. doi: 10.1007/s12325-020-01308-y. Epub 2020 Apr 18.

  PMID: 32303913 BACKGROUND

• Ozmert E, Arslan U. Management of toxic optic neuropathy via a combination of Wharton's jelly-derived mesenchymal stem cells with electromagnetic stimulation. Stem Cell Res Ther. 2021 Sep 27;12(1):518. doi: 10.1186/s13287-021-02577-2.

  PMID: 34579767 DERIVED

MeSH Terms

Conditions

Toxic Optic Neuropathy

Condition Hierarchy (Ancestors)

Optic Nerve Injuries; Cranial Nerve Injuries; Cranial Nerve Diseases; Nervous System Diseases; Optic Nerve Diseases; Craniocerebral Trauma; Trauma, Nervous System; Eye Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The cases were divided into 3 groups according to their similar demographic characteristics. Prospective open label

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 7, 2021
• Study Start: April 1, 2019
• Primary Completion: April 30, 2021
• Study Completion: April 30, 2021
• Last Updated: May 10, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

TU (2)