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Retinitis PigmentosaPhase 3WJ-MSCNCT04224207

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

A Phase 3 study testing Wharton's jelly derived mesenchymal stem cell in people with Retinitis Pigmentosa and Inherited Retinal Dystrophy, run by Ankara Universitesi Teknokent at 2 sites in Turkey (Türkiye).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 60 years
What is being tested?
Wharton's jelly derived mesenchymal stem cell
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
2 sitesTurkey (Türkiye)
Study dates
1 Apr 2019to 1 Jan 2020
Phase
Phase 3
Are there results?
None posted in the registry

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 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • • 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.

Who cannot join

  • • 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.

Trial locations and contacts

2 sites in 1 country.

Turkey (Türkiye)2 sites

  • Ankara University Biotechnology Institute

    Ankara, Türkiye, 06312

  • Umut Arslan

    Ankara, Türkiye, 06312

Other trials in Turkey (Türkiye)

About this study

Official title: Management of Retinitis Pigmentosa by Wharton's Jelly Derived Mesenchymal Stem Cells: Preliminary Clinical Results

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.

Read the 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.

Being tested
Wharton's jelly derived mesenchymal stem cell
Keywords
Retinitis pigmentosa, Wharton's jelly derived mesenchimal stem cell, Subtenon space, Umbilical cord
Medical subject headings
Retinitis Pigmentosa

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Wharton's jelly derived mesenchymal stem cellBiological

    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 .

Study groups in NCT04224207
Study groupRoleWhat they receive
Before applicationActive comparatorRP patients with progressive visual acuity and visual field loss: before stem cell application.
Receives: Biological: Wharton's jelly derived mesenchymal stem cell
After applicationActive comparatorRP patients, after stem cell applications.
Receives: Biological: Wharton's jelly derived mesenchymal stem cell

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ETDRS visual acuity

    The visual acuity scores obtained from the baseline testing and the final examination were analyzed and compared statistically to determine effectiveness.

    Measured: Change from baseline visual acuity at 6 months

Secondary outcomes (1)

  1. Outer retinal thickness

    This is the thickness from the outer plexiform layer to the Bruch membrane in the 3x3 mm area of the fovea measured (and recorded automatically) by the multimodal imaging OCTA device.

    Measured: Change from baseline outer retinal thickness at 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2020
  2. Study start1 Apr 2019
  3. Primary completion30 Oct 2019
  4. Study completion1 Jan 2020

Resources

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 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Prospective, open-label clinical trial; The statistical comparisons were made primarily between the baseline and final values from the same eye. The parametric results for visual functions and structural changes were analyzed.
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04224207
Sponsor's protocol ID
01.11.2018/01
Acronym
WJ-MSC
Status last verified
Jan 2020
First submitted
6 Jan 2020
Last updated
13 Jan 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 31013696

  • 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.

    PubMed 26107378

  • Rani S, Ryan AE, Griffin MD, Ritter T. Mesenchymal Stem Cell-derived Extracellular Vesicles: Toward Cell-free Therapeutic Applications. Mol Ther. 2015 May;23(5):812-823. doi: 10.1038/mt.2015.44. Epub 2015 Mar 19.

    PubMed 25868399

  • 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.

    PubMed 27116661

  • 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.

    PubMed 28157165

  • 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.

    PubMed 28164440

  • 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.

    PubMed 29553543

  • 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.

    PubMed 32787913

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Wharton's jelly derived mesenchymal stem cell in people with Retinitis Pigmentosa and Inherited Retinal Dystrophy, run by Ankara Universitesi Teknokent at 2 sites in Turkey (Türkiye).

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 6 inclusion and 4 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 13 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Turkey (Türkiye). 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 phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

ETDRS visual acuity (time frame: Change from baseline visual acuity at 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04224207, which also lists 8 linked publications.

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 13 Jan 2020.

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