Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
1 other identifier
interventional
50
1 country
1
Brief Summary
Retinitis pigmentosa (RP) is the most common hereditary retinal disorder (accounts for 20% of children attending blind schools in Pakistan) which causes degeneration of rod and cone photoreceptors. Rods and cones largely depend on the retinal pigment epithelium for their proper functioning. Various growth factors and their receptors are present in retinal epithelium and a number of genes are responsible for the production of these growth factors. Genetic mutation in any of these genes causes retinal degeneration by progressive loss of retinal pigment epithelium and photoreceptors. The disease initially starts with night blindness and leads to the loss of central vision and eventually total blindness. To date, there is no definitive cure for patients suffering from RP. Recently, stem cell based therapies have shown great promise for the management of RP. It is well documented that umbilical cord derived mesenchymal stem cells (UMSCs) have the ability to release various paracrine and immunomodulatory factors that are similar to those synthesized by retinal pigment epithelium. Multiple routes including systemic (intravenous) and localized (subretinal, intravitreal, suprachoroidal and sub-tenon) have been employed to administer UMSCs for the management of RP. It is important to note that deep sub-tenon region (space between the sclera and the conjunctiva) acts as both natural culture medium for cells and as immune privileged site because of avascularity of the region. It has been reported that the injection of UMSCs in sub-tenon space of human subjects have improved the visual acuity even after 1 year post-injection. In addition, the injection of UMSCs in suprachoroidal space enhances the entry of growth factors released by the cells into choroidal flow and maintain the constant growth factors secretion to the choroidal and retinal tissues. Limoli and colleagues were the first to report the suprachoroidal administration of cells being the safe mode of cell delivery with no complications. The present study is aimed to investigate the safety and therapeutic efficacy of UMSC injection employing two different routes (sub-tenon injection versus suprachoroidal injection) for the treatment of RP in human subjects.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Feb 2021
Shorter than P25 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2021
CompletedFirst Submitted
Initial submission to the registry
February 6, 2021
CompletedFirst Posted
Study publicly available on registry
February 21, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2022
CompletedFebruary 21, 2021
February 1, 2021
1.2 years
February 6, 2021
February 18, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Evaluation of safety related adverse ocular events including immune response
No significant side effects in stem cell treated subjects
Baseline to day 360
Ophthalmic examination for best-corrected visual acuity (BCVA) using early treatment of diabetic retinopathy study (ETDRS) chart
Change in best corrected visual acuity (BCVA)
Baseline to day 360
Secondary Outcomes (4)
Measurement of electrical activity/function of retina using Electroretinography (ERG) test
Baseline to day 360
Evaluation of outer retinal thickness using Optical Coherence Tomography (OCT) imaging test
Baseline to day 360
Examination of retinal damage by Fundus Photography
Baseline to day 360
Evaluation of visual field sensitivity using perimeter
Baseline to day 360
Study Arms (2)
Sub-tenon injection group
EXPERIMENTALIn total twenty five subjects will be treated by injecting UMSCs in sub-tenon space of eye.
Suprachoroidal injection group
EXPERIMENTALA total of twenty five subjects will be treated by suprachoroidal injection of UMSCs.
Interventions
Cultured stem cells will be injected in the sub-tenon space of eye and patients will be monitored and evaluated for outer retinal thickness, early treatment of diabetic retinopathy study visual acuity, visual field sensitivity, fundus photography, amplitudes of multifocal electroretinogram and implicit times of multifocal electroretinogram at baseline (day 0) and days 30, 60, 90, 180, 270 and 360.
Cultured stem cells will be injected in the suprachoroidal space of eye and patients will be monitored and evaluated for outer retinal thickness, early treatment of diabetic retinopathy study visual acuity, visual field sensitivity, fundus photography, amplitudes of multifocal electroretinogram and implicit times of multifocal electroretinogram at baseline (day 0) and days 30, 60, 90, 180, 270 and 360.
Eligibility Criteria
You may qualify if:
- Patients who will be voluntarily participated for UMSCs injection for the treatment of RP.
- Patients who will be able to adhere to the study follow-up and protocol requirements.
- Individuals with age ranges from 18 years to 70 years will be included.
- Patients with best corrected visual acuity (BCVA) from 50 letters to 110 letters or \<20/50 in the ETDRS chart testing (Topcon CC-100 XP, Japan).
- Mean deviation values ranging between -33.0 and - 5.0 dB with compass visual field analysis (threshold 24-2, Sita Standard, Stimulus 3-white).
- Diagnosis of any phenotypic or genotypic variation of RP, confirmed by clinical history, fundus appearance, visual field, electroretinogram and genetic mutation analysis.
You may not qualify if:
- Presence of cataracts or other media opacity that might affect the visual field, mean deviation, or electroretinogram recordings.
- Presence of another ocular disease except RP (i.e., uveitis, strabismus, glaucoma) that causes visual field and optic disc changes.
- Presence of any systemic disorder that may affect visual functions. This includes diabetes, neurological disorders, and uncontrolled systemic hypertension.
- Smokers will be excluded from the study.
- Individuals who underwent ocular surgery except cataract extraction will be considered as excluded.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Stem Cell laboratory, Jinnah Burn & Reconstructive Surgery Centre
Lahore, Punjab Province, 54550, Pakistan
Related Publications (6)
Kahraman NS, Oner A. Umbilical cord derived mesenchymal stem cell implantation in retinitis pigmentosa: a 6-month follow-up results of a phase 3 trial. Int J Ophthalmol. 2020 Sep 18;13(9):1423-1429. doi: 10.18240/ijo.2020.09.14. eCollection 2020.
PMID: 32953582BACKGROUNDAzam M, Collin RW, Malik A, Khan MI, Shah ST, Shah AA, Hussain A, Sadeque A, Arimadyo K, Ajmal M, Azam A, Qureshi N, Bokhari H, Strom TM, Cremers FP, Qamar R, den Hollander AI. Identification of novel mutations in Pakistani families with autosomal recessive retinitis pigmentosa. Arch Ophthalmol. 2011 Oct;129(10):1377-8. doi: 10.1001/archophthalmol.2011.290. No abstract available.
PMID: 21987686BACKGROUNDOzmert 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: 31931872BACKGROUNDOzmert 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: 32787913BACKGROUNDLimoli PG, Vingolo EM, Morales MU, Nebbioso M, Limoli C. Preliminary study on electrophysiological changes after cellular autograft in age-related macular degeneration. Medicine (Baltimore). 2014 Dec;93(29):e355. doi: 10.1097/MD.0000000000000355.
PMID: 25546695BACKGROUNDAli M, Mehmood A, Tarar MN, Nawaz Z, Riazuddin SA, Khan A, Riazuddin S. Efficacy of intravenous infusions of UC-derived MSCs for the treatment of COVID-19: A structured summary of a phase II double blinded, randomized controlled clinical trial. Preprint from Research Square, 28 Oct 2020. DOI: 10.21203/rs.3.rs-92995/v2
BACKGROUND
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sheikh Riazuddin, PhD
Jinnah Burn & Reconstructive Surgery Center, Lahore
- PRINCIPAL INVESTIGATOR
Zaheer-ud-Din A Qazi, consultant
The Layton Rahmatullah Benevolent Trust (LRBT)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER GOV
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Distinguished National Professor
Study Record Dates
First Submitted
February 6, 2021
First Posted
February 21, 2021
Study Start
February 1, 2021
Primary Completion
May 1, 2022
Study Completion
June 1, 2022
Last Updated
February 21, 2021
Record last verified: 2021-02