- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04238858
Effects of Subtenon-injected Autologous Platelet-rich Plasma on Visual Functions in Eyes With Retinitis Pigmentosa (PRP)
January 22, 2020 updated by: Umut Arslan, Ankara Universitesi Teknokent
Purpose One of the main reasons for apoptosis and dormant cell phases in degenerative retinal diseases such as retinitis pigmentosa (RP) is growth factor withdrawal in the cellular microenvironment.
Growth factors and neurotrophins can significantly slow down retinal degeneration and cell death in animal models.
One possible source of autologous growth factors is platelet-richplasma.The purpose of this study was to determine if subtenon injections of autologous platelet-rich plasma (aPRP) can have beneficial effects on visual function in RP patients by reactivating dormant photoreceptors.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
More than 240 genetic mutations are involved in inherited retinal dystrophies, which constitute an overlapping group of genetic and clinical heterogeneous disorders.
Retinitis pigmentosa (RP) is a heterogeneous genetic disorder (autosomal dominant, autosomal recessive, X-linked, or sporadic cases from spontaneous mutations) characterized by the progressive devolution of the retina and affecting 1/3000- 8000 people worldwide.
Symptoms include generally diminishing visual fields starting in the mid-periphery and advancing toward the fovea, ultimately leading to visual impairment and blindness with waxy-colored optic atrophy.
RP is also described as rod-cone dystrophy because of the primary degeneration of rods along with secondary degeneration of cones, with photoreceptor rods appearing to be more affected than cones.
Diseased photoreceptors face apoptosis,which results in reducing the thickness of the outer nuclear layer and the retinal pigment epithelium layer with abnormal pigmentary deposits.
Although apoptosis and photoreceptor loss are common outcomes of all genetic types, their clinical features and progression are not homogeneous.
It is currently known that while some photoreceptor cells do die, others appear to be in suspended animation .
In the photoreceptor microenvironment,when growth factor (GF) levels or their receptor activities decrease over an extended period, apoptosis and cell death occur.
The length of this period differs with each genetic type.
The time during which there is a decrease in the effects of growth factors until cell death, the photoreceptors can be described as being in sleep mode, on standby, or in a dormant phase.
In this phase, cone photoreceptors are alive, but they cannot function.
GFs and neurotrophins, such as basic fibroblast growth factor (bFGF), neural growth factor (NGF), ciliary neurotrophic factor (CNTF), and brain-derived neurotrophic factor (BDNF), can significantly slow retinal degeneration and cell death in animal models.
One possible source of autologous GFs is platelet-rich plasma (PRP).
PRP is defined as a biological product that features platelet concentration; it is collected from centrifuged whole blood.
Through the activation ofa reactivator (such as sodium chloride or citrate), accumulated platelets can secrete a large quantity of preparations rich in growth factors (PRGFs) via the release of intracellular α-granules.
PRGFs are an aggregation of cytokines that include transforming growth factors (TGF-β), interleukine-6 (IL-6), BDNF, and vascular endothelial growth factors (VEGF).
The strong restoring function of autologous PRP (aPRP) is based mainly on the trophic capacity of PRGFs .
Currently, PRP is being tested as a therapeutic option in some clinical situations, for example in orthopedics, ophthalmology, and healing therapies.
Some pre-clinical and clinical trials have addressed the use of PRP and various GFs, such as the intravitreal injection of bFGF in retinal dystrophy and the topical applications of NGF to treat glaucoma and neurotrophic keratitis.
The use of PRGFs in ophthalmology has been successfully applied to ocular surface disorders, including the treatment of ocular surface syndrome and flap necrosis after LASIK surgery.
A recent study observed that administration of platelet-derived proteins adjacent to the lacrimal gland restored lacrimal function in all patients.
The clinical and pre-clinical use of aPRP in ophthalmology has encouraged practitioners to use it through subtenon injection in the treatment of retinal diseases.
Through the subtenon injection of PRP, the level of neurotrophic growth factors may be increased in the microenvironment around the photoreceptors, thus potentially reactivating photoreceptors that are in sleep mode.Fetal bovine serum,allogeneic serum,and umbilical cord serum have also been used as sources of growth factors, but they are heterologous products with a higher risk of allergic reactions and infectious disease transmission.
In order to avoid these issues, and because of the accessibility and relatively safe nature of aPRP, we chose to use aPRP as a source of growth factors in our study.
The purpose of this prospective open-label clinical trial was to determine whether the subtenon injection of aPRP may have beneficial effects on visual functions-such as best corrected visual acuity (BCVA), visual field (VF), multifocal electroretinography (mfERG), and microperimetry (MP)-in RP patients with various degrees of narrowed visual fields.
Study Type
Interventional
Enrollment (Actual)
48
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Türkiye
-
Ankara, Türkiye, Turkey, 06312
- Ankara University Biotechnology Institute
-
-
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 55 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
18 years of age or older;
- Diagnosis of any phenotypic variation of RP, confirmed by clinical history, fundus appearance, VF, and electroretinogram;
- Experience of various degrees of VF loss;
- BCVA from light perception of up to 110 letters (equal to 1.6 decimal values) in early treatment of diabetic retinopathy study (ETDRS) chart testing (Topcon CC-100 XP, Japan); & Mean deviation (MD) values from-33.0 to-5.0 dB with Humphrey or Octopus 900 visual field analysis (threshold 30-2, Sita Standard, Stimulus 3-white);
- Intraocular pressure (IOP) <22 mmHg.
Exclusion Criteria:
The presence of cataracts or other media opacity that might affect the VF, MP, or mfERG 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 functions;
- The habit of smoking.
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 |
---|---|
Active Comparator: Before application
Forty-nine eyes belonging to 37 patients before injection aPRP.
|
blood is drawn from the patient's antecubital vein and inserted into four 3.0 ml vacutainer tubes that contain trisodium citrate.
These four tubes were placed in a centrifuge machine, and centrifugation was carried out at 2500 rpm (580×g) for 8 min within a 30-min blood collection period.
As a result of centrifugation, the plasma was separated in the vacutainer tubes from the remaining blood components.
Three different layers formed in the tubes: red blood cells at the bottom, aPRP in the middle layer, and aPPP in the top layer.
A total of 1.5 ml of the middle layer (which mainly contained platelets) was withdrawn by syringe, and it was immediately injected into the subtenon space of each eye.
|
No Intervention: After application
Forty-nine eyes belonging to 37 patients after injection aPRP.
|
|
Sham Comparator: Sham application
11 patients before - after aPPP injection
|
blood is drawn from the patient's antecubital vein and inserted into four 3.0 ml vacutainer tubes that contain trisodium citrate.
These four tubes were placed in a centrifuge machine, and centrifugation was carried out at 2500 rpm (580×g) for 8 min within a 30-min blood collection period.
As a result of centrifugation, the plasma was separated in the vacutainer tubes from the remaining blood components.
Three different layers formed in the tubes: red blood cells at the bottom, aPRP in the middle layer, and aPPP in the top layer.
A total of 1.5 ml of the middle layer (which mainly contained platelets) was withdrawn by syringe, and it was immediately injected into the subtenon space of each eye.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Visual field sensitivity
Time Frame: Change from baseline visual field sensitivity at 1 month
|
A Humphrey or Octopus 900 visual field analyzer, threshold 30-2 modality, was used at time points of 0,1,2,and 3.In addition, it was used three times before application during experimentation to exclude the learning effect.
The MD values, which were obtained from the baseline test and the final examination, were analyzed and compared statistically to make conclusions regarding effectiveness.
Visual field analysis could be properly performed on patients whose BCVA values were better than 50 letters in ETDRS chart testing (0.1 decimal)
|
Change from baseline visual field sensitivity at 1 month
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Umut Arslan, MD, Ankara Universitesi Teknokent
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
- Koenekoop RK. Why some photoreceptors die, while others remain dormant: lessons from RPE65 and LRAT associated retinal dystrophies. Ophthalmic Genet. 2011 Jun;32(2):126-8. doi: 10.3109/13816810.2010.544361. Epub 2011 Jan 26.
- Daftarian N, Kiani S, Zahabi A. Regenerative therapy for retinal disorders. J Ophthalmic Vis Res. 2010 Oct;5(4):250-64.
- Anitua E, Muruzabal F, Tayebba A, Riestra A, Perez VL, Merayo-Lloves J, Orive G. Autologous serum and plasma rich in growth factors in ophthalmology: preclinical and clinical studies. Acta Ophthalmol. 2015 Dec;93(8):e605-14. doi: 10.1111/aos.12710. Epub 2015 Apr 2.
- Arslan U, Ozmert E, Demirel S, Ornek F, Sermet F. Effects of subtenon-injected autologous platelet-rich plasma on visual functions in eyes with retinitis pigmentosa: preliminary clinical results. Graefes Arch Clin Exp Ophthalmol. 2018 May;256(5):893-908. doi: 10.1007/s00417-018-3953-5. Epub 2018 Mar 15.
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)
September 1, 2016
Primary Completion (Actual)
February 28, 2017
Study Completion (Actual)
January 30, 2018
Study Registration Dates
First Submitted
January 18, 2020
First Submitted That Met QC Criteria
January 22, 2020
First Posted (Actual)
January 23, 2020
Study Record Updates
Last Update Posted (Actual)
January 23, 2020
Last Update Submitted That Met QC Criteria
January 22, 2020
Last Verified
January 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 12-596-16
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.
Clinical Trials on Retinitis Pigmentosa
-
MeiraGTx UK II LtdSyne Qua Non Limited; Bionical EmasCompletedGene Therapy for X-linked Retinitis Pigmentosa (XLRP) - Retinitis Pigmentosa GTPase Regulator (RPGR)X-Linked Retinitis PigmentosaUnited Kingdom, United States
-
Oslo University HospitalRecruitingRetinitis Pigmentosa | Retinitis Pigmentosa 11Norway
-
Jinnah Burn and Reconstructive Surgery Centre,...The Layton Rahmatullah Benevolent Trust (LRBT) Free Eye Hospital, Township... and other collaboratorsRecruitingRetinitis Pigmentosa (RP)Pakistan
-
AbbVieActive, not recruitingAdvanced Retinitis PigmentosaUnited States
-
jCyte, IncCalifornia Institute for Regenerative Medicine (CIRM)CompletedRetinitis Pigmentosa (RP)United States
-
Janssen Research & Development, LLCJanssen Research & Development, LLCActive, not recruitingX-Linked Retinitis PigmentosaBelgium, Canada, United States, Israel, United Kingdom, Spain, Denmark, France, Italy, Netherlands, Switzerland
-
Janssen Research & Development, LLCActive, not recruitingX-Linked Retinitis PigmentosaUnited States, United Kingdom
-
GenSight BiologicsRecruitingNon-syndromic Retinitis PigmentosaUnited States, France, United Kingdom
-
Janssen Research & Development, LLCJanssen Research & Development, LLCActive, not recruitingX-Linked Retinitis PigmentosaUnited States, Canada, Israel, United Kingdom, Spain, Denmark, France, Belgium, Italy, Netherlands, Switzerland
-
BiogenCompletedX-Linked Retinitis PigmentosaUnited States, United Kingdom
Clinical Trials on Platelet rich plasma
-
Stanford UniversityPartnership for Clean CompetitionCompletedRheumatic Diseases | TendinopathyUnited States
-
VivaTech International, Inc.RecruitingOsteoarthritisUnited States
-
Genesis Athens ClinicNational and Kapodistrian University of AthensRecruitingMenopause, Premature | Menopausal Syndrome | Premature Ovarian Failure | Ovarian Failure, Premature | Menopause Related ConditionsGreece
-
Cardenal Herrera UniversityCompletedCarpal Tunnel SyndromeSpain
-
Damascus UniversityCompletedBone ResorptionSyrian Arab Republic
-
Peking University Third HospitalRecruiting
-
Rajavithi HospitalRecruitingAutologous Platelet-rich Plasma Supplement | Sperm Cryopreservation | Post-cryopreserved Sperm Quality | Semen AnalysisThailand
-
Matthew GettmanCompleted
-
Sutherland Medical CenterActive, not recruitingRotator Cuff Tears | Rotator Cuff TendinosisPoland
-
Skin Care and Laser Physicians of Beverly HillsEclipse Aesthetics, LLCUnknownAndrogenetic AlopeciaUnited States