Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton's Jelly Derived Mesenchymal Stem Cells

NCT ID: NCT04224207

Last Updated: 2020-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2020-01-01

Brief Summary

The aim of this study is to determine if umbilical cord Wharton's jelly derived mesenchymal stem cells implanted in sub-tenon space have beneficial effects on visual functions in retinitis pigmentosa patients by reactivating the degenerated photoreceptors in dormant phase.

Detailed Description

The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier between photoreceptor cells and choroidal blood vessels. Photoreceptor cells are vitally and functionally dependent on the RPE. The conversion of blood glucose to ATP, synthesis of proteins in the visual cycle and removal of metabolic waste takes place in the RPE. For these important processes, various peptide growth factors and their receptors are synthesized in the RPE. More than 260 genes in the RPE are responsible for the production of these peptide fragments. Mutations in any of these genes as well as ischemic, physical or chemical RPE damage causes retinal degeneration. Retinal degeneration may be inherited, such as in retinitis pigmentosa (RP), Stargardt's disease, choroideremia, Best vitelliform dystrophy and Bietti's crystalline dystrophy. Retinal degeneration may also be acquired through genetic mechanisms, such as age-releated macular degeneration. In retinal degeneration, there is a developing loss of RPE and photoreceptors, regardless of the underlying cause.

Umbilical cord Wharton's jelly derived mesenchymal stem cells (WJ-MSCs) have significant paracrine and immunomodulatory properties. WJ-MSCs secrete trophic factors that stimulate RPE or secrete trophic factors that are similar to those produced by RPE. In studies using animal models, WJ-MSCs have been found to be effective in stopping the progression of retinal degeneration and for rescuing photoreceptors in the dormant phase. WJ-MSCs are hypoimmunogenic and have significant immunomodulatory properties. WJ-MSCs have been shown to suppress chronic inflammation and prevent apoptosis in animal models of neurodegenerative and ischemic retinal disorders. WJ-MSCs also stimulate progenitor cells in the retina and elicit self-repair mechanisms.

The aim of this preliminary clinical study is to investigate the efficacy of deep sub-tenon injected WJ-MSCs as a stem cell treatment modality for the management of retinitis pigmentosa, which creates outer retinal degeneration. These functional and structural effects were investigated using microperimetry, electrophysiology and spectral domain optical coherence tomography (SD-OCT). To the best of our knowledge, this is the first prospective clinical study that utilizes a large number of RP cases, and cases that are in phase-3.

Conditions

Retinitis Pigmentosa; Inherited Retinal Dystrophy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Before application

RP patients with progressive visual acuity and visual field loss: before stem cell application.

Group Type: ACTIVE_COMPARATOR

Wharton's jelly derived mesenchymal stem cell

Intervention Type: BIOLOGICAL

The mesenchymal cells that were used in this study were isolated from Wharton's jelly of the umbilical cord that was collected allogenicly from a single donor with the mother's consent. All cell preparation and cultivation procedures were conducted in a current Good Manufacturing Practice (cGMP) accredited laboratory (Onkim Stem Cell Technologies, Turkey).Cells were solubilized from cryopreservation before being made ready for injection. Average cell viability for each treatment was over 90.0% and each patient received cell numbers between 2-6x106 in a 1.5 ml saline solution .

After application

RP patients, after stem cell applications.

Group Type: ACTIVE_COMPARATOR

Wharton's jelly derived mesenchymal stem cell

Intervention Type: BIOLOGICAL

The mesenchymal cells that were used in this study were isolated from Wharton's jelly of the umbilical cord that was collected allogenicly from a single donor with the mother's consent. All cell preparation and cultivation procedures were conducted in a current Good Manufacturing Practice (cGMP) accredited laboratory (Onkim Stem Cell Technologies, Turkey).Cells were solubilized from cryopreservation before being made ready for injection. Average cell viability for each treatment was over 90.0% and each patient received cell numbers between 2-6x106 in a 1.5 ml saline solution .

Interventions

Wharton's jelly derived mesenchymal stem cell

The mesenchymal cells that were used in this study were isolated from Wharton's jelly of the umbilical cord that was collected allogenicly from a single donor with the mother's consent. All cell preparation and cultivation procedures were conducted in a current Good Manufacturing Practice (cGMP) accredited laboratory (Onkim Stem Cell Technologies, Turkey).Cells were solubilized from cryopreservation before being made ready for injection. Average cell viability for each treatment was over 90.0% and each patient received cell numbers between 2-6x106 in a 1.5 ml saline solution .

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• • 18 years of age or older;

• Diagnosis of any phenotypic or genotypic variation of RP, confirmed by clinical history, fundus appearance, visual field (VF), electroretinogram (ERG) and genetic mutation analysis;
• Having experienced various degrees of VF loss;
• BCVA from 50 letters to 110 letters in the ETDRS chart testing (Topcon CC-100 XP, Japan);
• Mean deviation (MD) values ranging between -33.0 and -5.0 dB with Compass visual field analysis (threshold 24-2, Sita Standard, Stimulus 3-white);
• Intraocular pressure (IOP) of <22 mmHg.

Exclusion Criteria

• • The presence of cataracts or other media opacity that might affect the VF, MD, or ERG recordings;

• The presence of glaucoma, which causes visual field and optic disc changes;
• The presence of any systemic disorder (e.g.,diabetes, neurological disease, or uncontrolled systemic hypertension) that may affect visual function;
• The habit of smoking.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ankara Universitesi Teknokent

OTHER

Sponsor Role: lead

Responsible Party

Umut Arslan

Principle investigator, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Umut Arslan, MD

Role: PRINCIPAL_INVESTIGATOR

Ankara Universitesi Teknokent

Locations

Ankara University Biotechnology Institute

Ankara, Türkiye, Turkey (Türkiye)

Umut Arslan

Ankara, Türkiye, Turkey (Türkiye)

Countries

Turkey (Türkiye)

References

Musial-Wysocka A, Kot M, Sulkowski M, Badyra B, Majka M. Molecular and Functional Verification of Wharton's Jelly Mesenchymal Stem Cells (WJ-MSCs) Pluripotency. Int J Mol Sci. 2019 Apr 12;20(8):1807. doi: 10.3390/ijms20081807.

Reference Type: RESULT

PMID: 31013696 (View on PubMed)

Leow SN, Luu CD, Hairul Nizam MH, Mok PL, Ruhaslizan R, Wong HS, Wan Abdul Halim WH, Ng MH, Ruszymah BH, Chowdhury SR, Bastion ML, Then KY. Safety and Efficacy of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Therapy for Retinal Degeneration. PLoS One. 2015 Jun 24;10(6):e0128973. doi: 10.1371/journal.pone.0128973. eCollection 2015.

Reference Type: RESULT

PMID: 26107378 (View on PubMed)

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Reference Type: RESULT

PMID: 25868399 (View on PubMed)

Canto-Soler V, Flores-Bellver M, Vergara MN. Stem Cell Sources and Their Potential for the Treatment of Retinal Degenerations. Invest Ophthalmol Vis Sci. 2016 Apr 1;57(5):ORSFd1-9. doi: 10.1167/iovs.16-19127.

Reference Type: RESULT

PMID: 27116661 (View on PubMed)

Garg A, Yang J, Lee W, Tsang SH. Stem Cell Therapies in Retinal Disorders. Cells. 2017 Feb 2;6(1):4. doi: 10.3390/cells6010004.

Reference Type: RESULT

PMID: 28157165 (View on PubMed)

Mohamed EM, Abdelrahman SA, Hussein S, Shalaby SM, Mosaad H, Awad AM. Effect of human umbilical cord blood mesenchymal stem cells administered by intravenous or intravitreal routes on cryo-induced retinal injury. IUBMB Life. 2017 Mar;69(3):188-201. doi: 10.1002/iub.1608. Epub 2017 Feb 5.

Reference Type: RESULT

PMID: 28164440 (View on PubMed)

Limoli PG, Vingolo EM, Limoli C, Scalinci SZ, Nebbioso M. Regenerative Therapy by Suprachoroidal Cell Autograft in Dry Age-related Macular Degeneration: Preliminary In Vivo Report. J Vis Exp. 2018 Feb 12;(132):56469. doi: 10.3791/56469.

Reference Type: RESULT

PMID: 29553543 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32787913 (View on PubMed)

Other Identifiers

01.11.2018/01

Identifier Type: -

Identifier Source: org_study_id