Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)

February 18, 2021 updated by: Prof. Dr. Sheikh Riazuddin, Jinnah Burn and Reconstructive Surgery Centre, Lahore

Investigation of Therapeutic Efficacy and Safety of Umbilical Cord Derived Mesenchymal Stem Cells (UMSCs) for the Management of Retinitis Pigmentosa (RP)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Isolation and characterization of human umbilical cord derived mesenchymal stem cells (UMSCs): The culturing and characterization of UMSCs will be performed as documented by Ali and colleagues. Briefly, human umbilical cord tissues along with informed consent forms will be collected from COVID-19- and hepatitis B, C virus-negative women with healthy pregnancies during the Cesarean Section surgery after completion of gestation period. The umbilical cord tissue will be transported in sterile 1x phosphate-buffered saline (PBS) containing penicillin and streptomycin on ice. In the biosafety cabinet, the cord will be washed with 4-5 changes of sterile 1x PBS and placed in a Petri plate with 15ml PBS. The cord will then gently scrap with a surgical blade to remove any dead cells. A 9 cm umbilical cord will be cut into three equal pieces and wash thoroughly to remove blood clots, umbilical cord arteries, and veins. Segments will be washed three times with PBS and minced. The minced pieces will be incubated in 17.5ml of collagenase solution (201 U/ml collagenase type I in serum-free DMEM-HG) in a 50ml conical tube for ~3 hrs in an incubator at 5% CO2, 95% humidity at 37oC. After ~3 hrs, the digested lysate will be passed through strainer and will be diluted three times with 1x PBS. Following centrifugation, the cells will be seeded into two T-25cm2 flasks and will be placed in an incubator at 5% CO2, 95% humidity at 37o C. The flasks will be fed with fresh media (DMEM-HG supplemented with 20% FBS and 1% antibiotic solution) every third day. At around day 18, cells will reach up to 85% confluency and will be transferred in two T-75cm2 flasks with media replaced at alternate days. UMSCs at P3 will be characterized using different specific antibodies. Cells at P3 will be employed for injection in RP patients.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Pakistan
    • Punjab
      • Lahore, Punjab, Pakistan, 54550
        • Recruiting
        • Stem Cell laboratory, Jinnah Burn & Reconstructive Surgery Centre
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sub-tenon injection group
In total twenty five subjects will be treated by injecting UMSCs in sub-tenon space of eye.
Biological: Injection of stem cells in sub-tenon space of eye for the management of retinitis pigmentosa
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.
Experimental: Suprachoroidal injection group
A total of twenty five subjects will be treated by suprachoroidal injection of UMSCs.
Biological: Injection of stem cells in suprachoroidal space of eye for the management of Retinitis Pigmentosa
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of safety related adverse ocular events including immune response
Time Frame: Baseline to day 360
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
Time Frame: Baseline to day 360
Change in best corrected visual acuity (BCVA)
Baseline to day 360

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of electrical activity/function of retina using Electroretinography (ERG) test
Time Frame: Baseline to day 360
Change in electrical response/function of various cell types of retina
Baseline to day 360
Evaluation of outer retinal thickness using Optical Coherence Tomography (OCT) imaging test
Time Frame: Baseline to day 360
Alteration in retinal thickness
Baseline to day 360
Examination of retinal damage by Fundus Photography
Time Frame: Baseline to day 360
Change in retinal Fundus image
Baseline to day 360
Evaluation of visual field sensitivity using perimeter
Time Frame: Baseline to day 360
Change in visual field sensitivity
Baseline to day 360

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jinnah Burn and Reconstructive Surgery Centre, Lahore

Collaborators

The Layton Rahmatullah Benevolent Trust (LRBT) Free Eye Hospital, Township Lahore.
Centre of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore.

Investigators

  • 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)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

February 1, 2021

Primary Completion (Anticipated)

May 1, 2022

Study Completion (Anticipated)

June 1, 2022

Study Registration Dates

First Submitted

February 6, 2021

First Submitted That Met QC Criteria

February 18, 2021

First Posted (Actual)

February 21, 2021

Study Record Updates

Last Update Posted (Actual)

February 21, 2021

Last Update Submitted That Met QC Criteria

February 18, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JB&RSC-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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