WJ-MSC: Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton's Jelly Derived Mesenchymal Stem Cells

Sponsor

Ankara Universitesi Teknokent (Other)

Overall Status

Completed

CT.gov ID

NCT04224207

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Retinitis Pigmentosa Inherited Retinal Dystrophy	Biological: Wharton's jelly derived mesenchymal stem cell	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 1, 2019

Actual Primary Completion Date :

Oct 30, 2019

Actual Study Completion Date :

Jan 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Before application RP patients with progressive visual acuity and visual field loss: before stem cell application.	Biological: 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 .
Active Comparator: After application RP patients, after stem cell applications.	Biological: 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 .

Arm

Intervention/Treatment

Active Comparator: Before application

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

Biological: 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 .

Active Comparator: After application

RP patients, after stem cell applications.

Biological: Wharton's jelly derived mesenchymal stem cell

Outcome Measures

Primary Outcome Measures

ETDRS visual acuity [Change from baseline visual acuity at 6 months]
The visual acuity scores obtained from the baseline testing and the final examination were analyzed and compared statistically to determine effectiveness.

Secondary Outcome Measures

Outer retinal thickness [Change from baseline outer retinal thickness at 6 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.