Management of Retinitis Pigmentosa Via Combination of Wharton's Jelly-derived Mesenchymal Stem Cells and Magnovision

NCT05800301 | Completed Phase 3 DMC

• 1 other identifier: 11-962-19
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

Purpose To investigate whether the natural progression rate of retinitis pigmentosa (RP) can be decreased with subtenon umbilical cord Wharton's jelly derived mesenchymal stemcell (WJ-MSC) application alone or combination with retinal electromagnetic stimulation (rEMS). Material and methods The study included prospective analysis of 130 eyes of 80 retinitis pigmentosa patients with a 36-month follow-up duration. Patients constitute 4 groups with similar demographic characteristics. The subtenon WJ-MSC only group consisted of 34 eyes of 32 RP patients as Group1; The rEMS only group consisted of 32 eyes of 16 RP patients as Group2; The combined management group consisted of 32 eyes of 16 RP patients who received combined WJ-MSC and rEMS as Group3; The natural course (control) group consisted of 32 eyes of 16 RP patients who did not receive any treatment were classified as Group4. Fundus autofluorescence surface area (FAF-field), horizontal and vertical ellipsoid zone width (EZW), fundus perimetry deviation index (FPDI), full field electroretinography magnitude (ERG-m) and best corrected visual acuity (BCVA) changes were compared within and between groups after 36 month follow up period.

Conditions

Retinitis Pigmentosa

Keywords

Retinitis pigmentosa,; stemcell; Wharton jelly; umbilical cord; mesenchymal stemcell; electromagnetic stimulation; iontophoresis; Magnovision.

Outcome Measures

Primary Outcomes (1)

• Fundus autofluorescence surface area (FAF-field):

  The pattern of FAF correlates well with functional tests such as perimetry and ERG. The ring of increased autofluorescence appears to represent the border between functional and dysfunctional retinas. Metabolically active photoreceptors/RPE appear as hyperfluorescent areas in the FAF device due to the presence of lipofuscin. The FAF device calculated the FAF field automatically after marking the horizontal and vertical longest axes of the hyperfluorescent field in the posterior pole.

  Change between the 36th month (Time1) and baseline (Time0) values.

Secondary Outcomes (4)

• ETDRS visual acuity (BCVA):

  Change between the 36th month (Time1) and baseline (Time0) values.

• Ellipsoid zone widths (EZW):

  Change between the 36th month (Time1) and baseline (Time0) values.

• Fundus perimetry deviation index (FPDI):

  Change between the 36th month (Time1) and baseline (Time0) values.

• Full-field multi-luminance flicker electroretinography magnitude (ERG-m):

  Change between the 36th month (Time1) and baseline (Time0) values.

Study Arms (4)

Only WJ-MSCs

ACTIVE COMPARATOR

Consisted of 34 eyes of 32 RP patients treated with only WJ-MSCs, and it was applied only once following necessary preparations. After the inoculation of stem cells, the patients were followed up regularly on the 10th day, 3rd month, and every 6 months after that until 36 th months. For ethical reasons, the worse eye was selected to inject the stem cells instead of both eyes.

Biological: Wharton's jelly derived mesenchymal stemcells

Only rEMS

ACTIVE COMPARATOR

Consisted of 32 eyes of 16 RP patients treated with only rEMS. rEMS was applied with a custom-designed helmet once a week for 30 min for 36 months. Both eyes are stimulated at the same time with the specially designed system for ophthalmologic use (MagnoVisionTM).

Device: Magnovision

WJ-MSCs and rEMS combination

ACTIVE COMPARATOR

Consisted of 32 eyes of 16 RP patients treated with the WJ-MSCs and rEMS combination. WJ-MSCs were applied first into the deep subtenon space of both eyes after necessary preparations. rEMS application was started 10 days after the WJ-MSC application with a custom-designed helmet for 30 min. WJ-MSCs were inoculated only once, and rEMS was applied regularly once a week for 30 min for 36 months. Both eyes are stimulated at the same time with the specially designed system for ophthalmologic use (MagnoVisionTM).

Biological: Wharton's jelly derived mesenchymal stemcells; Device: Magnovision

The natural course

NO INTERVENTION

The natural course (control) group consisted of 32 eyes of 16 RP patients who received no treatment and were regularly followed until the 36th month. This group comprised patients who did not accept any treatment and/or were in good condition at baseline.

Interventions

Wharton's jelly derived mesenchymal stemcells BIOLOGICAL

The WJ-MSCs suspension from the culture was delivered to the operating room by cold chain and used within 24 h. A total of 1.5 ml of the WJ-MSC suspension was immediately injected into the deep subtenon space of each eye.

Only WJ-MSCs; WJ-MSCs and rEMS combination

Magnovision DEVICE

Specifically designed helmets producing high-frequency repetitive electromagnetic stimulation (MagnovisionTM, Bioretina Biotechnology, Ankara, Türkiye) stimulated the retinas and visual pathways in both eyes.

Also known as: Electromagnetic stimulator, iontophoresis, neuromodulator

Only rEMS; WJ-MSCs and rEMS combination

Eligibility Criteria

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

You may qualify if:

• RP patients of any genotype and phenotype;
• BCVA better than 35 letters;
• Any degree and kind of visual field loss;
• Over 18 years old.

You may not qualify if:

• The presence of glaucoma,
• Dense cataracts
• Dense vitreus opacities
• Autoimmune retinopathy-like clinical picture
• Any degree of smoking
• Presence of systemic neurological disease with seizure
• Presence of a cardiac pacemaker.

Sponsors & Collaborators

• Ankara Universitesi Teknokent: lead

Study Sites (3)

BioRetina

Ankara, Gölbaşı, 06570, Turkey (Türkiye)

Location

Ankara University Biotechnology Institute

Ankara, Türkiye, 06312, Turkey (Türkiye)

Location

Umut Arslan

Ankara, 06000, Turkey (Türkiye)

Location

Related Publications (7)

• 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. 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 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• Ozmert E, Arslan U. Management of Retinitis Pigmentosa Via Wharton's Jelly-Derived Mesenchymal Stem Cells or Combination With Magnovision: 3-Year Prospective Results. Stem Cells Transl Med. 2023 Oct 5;12(10):631-650. doi: 10.1093/stcltm/szad051.

  PMID: 37713598 DERIVED

MeSH Terms

Conditions

Retinitis Pigmentosa

Interventions

Iontophoresis

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Electrophoresis; Electrochemical Techniques; Investigative Techniques

Study Design

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

Model Details: A total of 130 eyes of 80 RP patients who could be checked regularly, mean 36 months of the follow-up period, were included in this study. Four different groups with similar demographic characteristics were created in the cohort

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: April 5, 2023
• Study Start: January 1, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2022
• Last Updated: April 5, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

TU (3)