The Effect of Stem Cells and Stem Cell Exosomes on Visual Functions in Patients With Retinitis Pigmentosa

NCT05413148 | Unknown Phase 2 DMC

• 1 other identifier: TSG-2021-11599.
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial aims to study the efficacy of umbilical cord-derived mesenchymal stem cells and their exosomes in the treatment of retinitis pigmentosa. The participants will be randomized into 3 groups. Functional and structural parameters will be compared before and after the injections and also will be compared among the groups to reveal whether stem cell and their exosomes are more effective than placebo.

Conditions

Retinitis Pigmentosa

Keywords

wharton jelly derived; mesenchymal stem cell; exosome

Outcome Measures

Primary Outcomes (2)

• Evaluation of best corrected visual acuity change

  Visual acuity change with LogMar Chart

  Upto 6 months

• Evaluation of visual field change

  Mean deviation values of automatic visual field testing

  Upto 6 months

Secondary Outcomes (4)

• Evaluation of multifocal ERG changes

  Upto 6 months

• Evaluation of ERG changes

  Upto 6 months

• Evaluation of optical coherence tomography changes

  Upto 6 months

• Evaluation of optical coherence tomography angiography changes

  Upto 6 months

Study Arms (3)

Wharton jelly-derived mesenchymal stem cell

ACTIVE COMPARATOR

Single subtenon injection of Wharton jelly-derived mesenchymal stem cells will be performed on a single eye after randomization

Biological: Subtenon injection of Wharton jelly derived mesenchymal stem cells

Mesenchymal stem cell exosome (Wharton jelly-derived)

ACTIVE COMPARATOR

Single subtenon injection of mesenchymal stem cell exosomes (Wharton jelly-derived)will be performed on a single eye after randomization.

Biological: Subtenon injection of Wharton jelly derived mesenchymal stem cell exosomes

Placebo

PLACEBO COMPARATOR

A single subtenon injection of saline will be performed on a single eye after randomization.

Other: Placebo

Interventions

Subtenon injection of Wharton jelly derived mesenchymal stem cells BIOLOGICAL

Single subtenon's injection for single eye

Wharton jelly-derived mesenchymal stem cell

Subtenon injection of Wharton jelly derived mesenchymal stem cell exosomes BIOLOGICAL

Single subtenon's injection for single eye

Mesenchymal stem cell exosome (Wharton jelly-derived)

Placebo OTHER

Single Subtenon injection of saline for a single eye

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years and over,
• Diagnosis of retinitis pigmentosa: by clinical history, fundus examination, visual field (GA), electroretinogram (ERG), and genetic analysis
• Visual field loss
• The best corrected visual acuity of 0.05 on the Snellen chart
• The MD (mean deviation) value in the visual field is between 33.0 and -5.0 dB
• Intraocular pressure value below 22 mmHg

You may not qualify if:

• Presence of cataracts or other media opacities that may affect imaging and tests
• Diagnosis of glaucoma
• History of ocular surgery or injection in the last 6 months
• Visual level too low for examinations (0.05 and below)
• Diagnosis of any systemic disease (such as diabetes, uncontrolled hypertension, neurological disease)
• Smoking and substance abuse

Sponsors & Collaborators

• TC Erciyes University: lead

Study Sites (1)

Erciyes University, Faculty of Medicine

Kayseri, 38039, Turkey (Türkiye)

RECRUITING

Related Publications (24)

• Limoli PG, Limoli CSS, Morales MU, Vingolo EM. Mesenchymal stem cell surgery, rescue and regeneration in retinitis pigmentosa: clinical and rehabilitative prognostic aspects. Restor Neurol Neurosci. 2020;38(3):223-237. doi: 10.3233/RNN-190970.

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• Bhattacharya S, Gangaraju R, Chaum E. Recent Advances in Retinal Stem Cell Therapy. Curr Mol Biol Rep. 2017 Sep;3(3):172-182. doi: 10.1007/s40610-017-0069-3. Epub 2017 Jul 10.

  PMID: 29152454 BACKGROUND

• Limoli PG, Vingolo EM, Limoli C, Nebbioso M. Stem Cell Surgery and Growth Factors in Retinitis Pigmentosa Patients: Pilot Study after Literature Review. Biomedicines. 2019 Nov 30;7(4):94. doi: 10.3390/biomedicines7040094.

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• Borkowska-Kuczkowska A, Slugocka D, Swiatkowska-Flis B, Boruczkowski D. The use of mesenchymal stem cells for the treatment of progressive retinal diseases: a review. Regen Med. 2019 May;14(4):321-329. doi: 10.2217/rme-2019-0022. Epub 2019 Apr 12.

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• Jin ZB, Gao ML, Deng WL, Wu KC, Sugita S, Mandai M, Takahashi M. Stemming retinal regeneration with pluripotent stem cells. Prog Retin Eye Res. 2019 Mar;69:38-56. doi: 10.1016/j.preteyeres.2018.11.003. Epub 2018 Nov 9.

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• 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

• Oner A. Stem Cell Treatment in Retinal Diseases: Recent Developments. Turk J Ophthalmol. 2018 Feb;48(1):33-38. doi: 10.4274/tjo.89972. Epub 2018 Feb 23.

  PMID: 29576896 BACKGROUND

• Cotrim CC, Jorge R, Oliveira MC, Pieroni F, Messias AMV, Siqueira RC. Clinical studies using stem cells for treatment of retinal diseases: state of the art. Arq Bras Oftalmol. 2020 Mar-Apr;83(2):160-167. doi: 10.5935/0004-2749.20200037.

  PMID: 32159599 BACKGROUND

• Huo DM, Dong FT, Yu WH, Gao F. Differentiation of mesenchymal stem cell in the microenviroment of retinitis pigmentosa. Int J Ophthalmol. 2010;3(3):216-9. doi: 10.3980/j.issn.2222-3959.2010.03.08. Epub 2010 Sep 18.

  PMID: 22553557 BACKGROUND

• Satarian L, Nourinia R, Safi S, Kanavi MR, Jarughi N, Daftarian N, Arab L, Aghdami N, Ahmadieh H, Baharvand H. Intravitreal Injection of Bone Marrow Mesenchymal Stem Cells in Patients with Advanced Retinitis Pigmentosa; a Safety Study. J Ophthalmic Vis Res. 2017 Jan-Mar;12(1):58-64. doi: 10.4103/2008-322X.200164.

  PMID: 28299008 BACKGROUND

• Kuriyan AE, Albini TA, Townsend JH, Rodriguez M, Pandya HK, Leonard RE 2nd, Parrott MB, Rosenfeld PJ, Flynn HW Jr, Goldberg JL. Vision Loss after Intravitreal Injection of Autologous "Stem Cells" for AMD. N Engl J Med. 2017 Mar 16;376(11):1047-1053. doi: 10.1056/NEJMoa1609583.

  PMID: 28296617 BACKGROUND

• Harrell CR, Fellabaum C, Jovicic N, Djonov V, Arsenijevic N, Volarevic V. Molecular Mechanisms Responsible for Therapeutic Potential of Mesenchymal Stem Cell-Derived Secretome. Cells. 2019 May 16;8(5):467. doi: 10.3390/cells8050467.

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• Klingeborn M, Dismuke WM, Bowes Rickman C, Stamer WD. Roles of exosomes in the normal and diseased eye. Prog Retin Eye Res. 2017 Jul;59:158-177. doi: 10.1016/j.preteyeres.2017.04.004. Epub 2017 Apr 29.

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• Harrell CR, Simovic Markovic B, Fellabaum C, Arsenijevic A, Djonov V, Arsenijevic N, Volarevic V. Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases. Adv Exp Med Biol. 2018;1089:47-57. doi: 10.1007/5584_2018_219.

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• Mead B, Tomarev S. Extracellular vesicle therapy for retinal diseases. Prog Retin Eye Res. 2020 Nov;79:100849. doi: 10.1016/j.preteyeres.2020.100849. Epub 2020 Mar 10.

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• Yaghoubi Y, Movassaghpour A, Zamani M, Talebi M, Mehdizadeh A, Yousefi M. Human umbilical cord mesenchymal stem cells derived-exosomes in diseases treatment. Life Sci. 2019 Sep 15;233:116733. doi: 10.1016/j.lfs.2019.116733. Epub 2019 Aug 5.

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• Zhang X, Liu J, Yu B, Ma F, Ren X, Li X. Effects of mesenchymal stem cells and their exosomes on the healing of large and refractory macular holes. Graefes Arch Clin Exp Ophthalmol. 2018 Nov;256(11):2041-2052. doi: 10.1007/s00417-018-4097-3. Epub 2018 Aug 30.

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• Yu B, Shao H, Su C, Jiang Y, Chen X, Bai L, Zhang Y, Li Q, Zhang X, Li X. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1. Sci Rep. 2016 Sep 30;6:34562. doi: 10.1038/srep34562.

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MeSH Terms

Conditions

Retinitis Pigmentosa

Condition Hierarchy (Ancestors)

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

Study Officials

• Kuddusi ERKILIÇ, Professor

  Erciyes University Medical Faculty

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Osman Ahmet POLAT, MD

CONTACT

905424395196; osmanahmet@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 28, 2022
• First Posted: June 9, 2022
• Study Start: August 5, 2022
• Primary Completion: July 1, 2023
• Study Completion: December 15, 2023
• Last Updated: September 7, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)