The Effect of Stem Cells and Stem Cell Exosomes on Visual Functions in Patients With Retinitis Pigmentosa

September 5, 2022 updated by: Kuddusi Erkılıç, TC Erciyes University

The Effect of Wharton Jelly-derived Mesenchymal Stem Cells and Stem Cell Exosomes on Visual Functions in Patients With Retinitis Pigmentosa

This clinical trial aims to study the efficacy of umbilical cord-derived mesenchymal stem cells and their exosomes in the treatment of retinitis pigmentosa. The participants will be randomized into 3 groups. Functional and structural parameters will be compared before and after the injections and also will be compared among the groups to reveal whether stem cell and their exosomes are more effective than placebo.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Retinitis pigmentosa (RP) is one of the leading causes of vision loss and irreversible blindness. It is stated that 1.4 million people are affected in the world and its prevalence is 1:4000. Stem cell applications are methods that are increasingly gaining importance in the field of regenerative medicine and ophthalmology. In addition to many experimental studies in retinal diseases including retinitis pigmentosa, there are also clinical studies reporting successful results on humans. The most widely used stem-cell group in current clinical practice is mesenchymal stem cells. The advantages are that they are relatively easy to obtain and do not induce severe immune responses. Clinical studies in stem cell therapies for the eye suggest that stem cells benefit the surrounding tissue by secreting support such as growth factors, and extracellular vesicles, mostly due to their trophic and paracrine effects. In intraocular applications, there has been a tendency to apply mesenchymal stem cells around/outside the eye, including subtenon and suprachoroidal application due to side effects such as retinal detachment and epiretinal membrane.

Other cellular products that have been studied in animal studies and clinical research in recent years are exosomes. Exosomes are a subgroup of extracellular vesicles released from cells. Exosomes are extracellular vesicles 30-150 nm in size and carry at least one of the exosomal proteins CD63, CD9, CD81, syntenin-1 and TSG101. Exosomes are secreted from different cells in the organism and are also found in body fluids. Exosomes play a role in the transportation of biomolecules such as lipids, carbohydrates, nucleic acids and proteins from one cell to another and in this way, they function in genetic information transfer, and reprogramming of the opposite cell and intercellular communication. One of the sources of exosomes is mesenchymal stem cells that secrete high amount of exosomes. Mesenchymal stem cell-derived exosomes have been reported to have therapeutic effects, just like mesenchymal stem cells. It is thought that stem cells also exert their clinical effects through paracrine factors they secrete rather than being implanted in the tissue. However, the mechanism of action of mesenchymal stem cells has not been fully understood, and exosomes are thought to contribute to the effect. The storage and durability of exosomes may provide advantages in therapeutic applications compared to mesenchymal stem cells and may provide more immunological advantages in allogeneic applications compared to cellular treatments since they do not contain cells.

One of the sources from which mesenchymal stem cells can be obtained is Wharton jelly, which is the mesenchymal tissue of the umbilical cord. Stem cells originating from Wharton gel are a good source of stem cells due to their high differentiation capacity, high regeneration capacity, constant doubling time, high proliferation capacity, low immunogenicity, and no ethical problems due to non-invasive methods, and easy availability.

This clinical trial will enroll patients diagnosed with retinitis pigmentosa. The diagnosis of RP is made by clinical fundus examination, examinations in our clinic, and genetic analysis.

At the beginning of the study, all volunteers will undergo a full ophthalmologic examination including best-corrected visual acuity, anterior segment and fundus examination with a slit lamp, OCT (optical coherence tomography), VF (visual field), ERG (electroretinogram), mfERG (multifocal ERG), OCTA (optical coherence tomography). Retinal and choroidal thickness and ellipsoid bandwidth in OCT, MD (mean deviation) value showing sensitivity in VF, amplitude and latency times in ERG and mf-ERG, vascular density and vascular flow ratios in OCTA will be recorded.

The volunteers will be randomized into three. The 1st group will be the placebo group (45 volunteers) and 0.5 cc saline physiological saline will be applied to the subtenon space. 2nd group of patients (45 volunteers) will undergo a subtenon injection of Wharton gel-derived mesenchymal stem cell suspension. A suspension containing mesenchymal stem cell exosomes from Wharton jelly will be applied to the subtenon distance to the 3rd group of patients (45 volunteers). A single eye of each volunteer will be included. Informed consent will be obtained from the volunteers.

Allogeneic human Wharton gel tissue-derived mesenchymal stem cells and their exosomes will be obtained from healthy female volunteers, who is over 18 years old, under sterile conditions after HBV, HCV, HIV virus and "Treponema Pallidum" (VDRL) tests were performed. Cord tissue obtained from birth will be carried in a sterile transfer solution and will be processed to obtain stem cells in Erciyes University Genome and Stem Cell GMP (good manufacturing practices) certified laboratories. Exosomes will be obtained by the ultracentrifugation method in the same facility.

For injection into the subtenon distance, the conjunctiva and tenon will be opened with a small incision about 10 mm away from the lower temporal area, then 20 gauge curved subtenon cannula will be advanced parallel to the sclera and injected into the posterior subtenon area. All volunteers will be prescribed antibiotics and steroid drops after the surgical procedure.

Full ophthalmological examination and examinations at the beginning of the study will be performed and recorded again on the 1st day, 1st month, 2nd month, 3rd month and 6th months of the anterior segment and fundus examination, OCT (optical coherence tomography), VF (visual field) ), ERG (electroretinogram), mfERG (multifocal ERG), OCTA (optical coherence tomography) examinations will be performed.

In addition, a questionnaire evaluating the visual functions subjectively will be administered at the 1st, 3rd and 6th-month visits. (National Eye Institute Visual Functioning Questionnaire - 25 / National Eye Institute (USA) Visual Function Questionnaire ). Two masked investigators will perform analyses.

Post-procedure 1st Day, 1st Month, 2nd Month, 3rd Month and 6th Month data will be compared among study groups and within groups.

Study Type

Interventional

Enrollment (Anticipated)

135

Phase

  • Phase 2
  • Phase 3

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

  • Turkey
      • Kayseri, Turkey, 38039
        • Recruiting
        • Erciyes University, Faculty of Medicine
        • 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

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18 years and over,
  • Diagnosis of retinitis pigmentosa: by clinical history, fundus examination, visual field (GA), electroretinogram (ERG), and genetic analysis
  • Visual field loss
  • The best corrected visual acuity of 0.05 on the Snellen chart
  • The MD (mean deviation) value in the visual field is between 33.0 and -5.0 dB
  • Intraocular pressure value below 22 mmHg

Exclusion Criteria:

  • Presence of cataracts or other media opacities that may affect imaging and tests
  • Diagnosis of glaucoma
  • History of ocular surgery or injection in the last 6 months
  • Visual level too low for examinations (0.05 and below)
  • Diagnosis of any systemic disease (such as diabetes, uncontrolled hypertension, neurological disease)
  • Smoking and substance abuse

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Wharton jelly-derived mesenchymal stem cell
Single subtenon injection of Wharton jelly-derived mesenchymal stem cells will be performed on a single eye after randomization
Biological: Subtenon injection of Wharton jelly derived mesenchymal stem cells
Single subtenon's injection for single eye
Active Comparator: Mesenchymal stem cell exosome (Wharton jelly-derived)
Single subtenon injection of mesenchymal stem cell exosomes (Wharton jelly-derived)will be performed on a single eye after randomization.
Biological: Subtenon injection of Wharton jelly derived mesenchymal stem cell exosomes
Single subtenon's injection for single eye
Placebo Comparator: Placebo
A single subtenon injection of saline will be performed on a single eye after randomization.
Other: Placebo
Single Subtenon injection of saline for a single eye

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of best corrected visual acuity change
Time Frame: Upto 6 months
Visual acuity change with LogMar Chart
Upto 6 months
Evaluation of visual field change
Time Frame: Upto 6 months
Mean deviation values of automatic visual field testing
Upto 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of multifocal ERG changes
Time Frame: Upto 6 months
Amplitudes changes in multifocal ERG testing
Upto 6 months
Evaluation of ERG changes
Time Frame: Upto 6 months
Amplitude changes in multifocal ERG testing
Upto 6 months
Evaluation of optical coherence tomography changes
Time Frame: Upto 6 months
Retinal thickness changes in optical coherence tomography change
Upto 6 months
Evaluation of optical coherence tomography angiography changes
Time Frame: Upto 6 months
Vascular density changes in optical coherence tomography angiography
Upto 6 months

Collaborators and Investigators

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

Sponsor

TC Erciyes University

Investigators

  • Principal Investigator: Kuddusi ERKILIÇ, Professor, Erciyes University Medical Faculty

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 (Actual)

August 5, 2022

Primary Completion (Anticipated)

July 1, 2023

Study Completion (Anticipated)

December 15, 2023

Study Registration Dates

First Submitted

May 28, 2022

First Submitted That Met QC Criteria

June 7, 2022

First Posted (Actual)

June 9, 2022

Study Record Updates

Last Update Posted (Actual)

September 7, 2022

Last Update Submitted That Met QC Criteria

September 5, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TSG-2021-11599.

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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