Retinitis PigmentosaPRPNCT04238858
Effects of Subtenon-injected Autologous Platelet-rich Plasma on Visual Functions in Eyes With Retinitis Pigmentosa
A study testing Platelet rich plasma in people with Retinitis Pigmentosa, run by Ankara Universitesi Teknokent at 1 site in Turkey (Türkiye).
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Retinitis Pigmentosa
- What is being tested?
- Platelet rich plasma
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Sep 2016to 30 Jan 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Ankara University Biotechnology Institute
Ankara, Türkiye, 06312
About this study
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.
Read the 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.
- Conditions
- Retinitis Pigmentosa
- Being tested
- Platelet rich plasma
- Keywords
- Retinitis pigmentosa, Growth factors, Platelet rich plasma, Visual functions
- Medical subject headings
- Retinitis Pigmentosa
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Platelet rich plasmaBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Before application | Active comparator | Forty-nine eyes belonging to 37 patients before injection aPRP. Receives: Biological: Platelet rich plasma |
| After application | No intervention | Forty-nine eyes belonging to 37 patients after injection aPRP. |
| Sham application | Sham comparator | 11 patients before - after aPPP injection Receives: Biological: Platelet rich plasma |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual field sensitivity
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)
Measured: Change from baseline visual field sensitivity at 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2020
- Study start1 Sep 2016
- Primary completion28 Feb 2017
- Study completion30 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Retinitis PigmentosaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective open-label, before-after-control group comparisions
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ankara Universitesi Teknokent
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Umut Arslan, Ankara Universitesi Teknokent
- Investigators
- Umut Arslan, MD, Principal investigator, Ankara Universitesi Teknokent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04238858
- Sponsor's protocol ID
- 12-596-16
- Acronym
- PRP
- Status last verified
- Jan 2020
- First submitted
- 18 Jan 2020
- Last updated
- 23 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 21268677Daftarian N, Kiani S, Zahabi A. Regenerative therapy for retinal disorders. J Ophthalmic Vis Res. 2010 Oct;5(4):250-64.
PubMed 22737370Anitua 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.
PubMed 25832910Arslan 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.
PubMed 29546474
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Subtenon-injected Autologous Platelet-rich Plasma on Visual Functions in Eyes With Retinitis Pigmentosa
- ClinicalTrials.gov ID
- NCT04238858
- Acronym / sponsor ID
- PRP / 12-596-16
- Conditions
- Retinitis Pigmentosa
- Keywords
- Retinitis pigmentosa, Growth factors, Platelet rich plasma, Visual functions
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Ankara Universitesi TeknokentUniversity, hospital or other
- Study start
- 1 Sep 2016 (actual)
- Primary completion
- 28 Feb 2017 (actual)
- Study completion
- 30 Jan 2018 (actual)
- First posted
- 23 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Prospective open-label, before-after-control group comparisions
| Arm | Type | Receives |
|---|---|---|
| Before application | Active comparator | Biological: Platelet rich plasmaForty-nine eyes belonging to 37 patients before injection aPRP. |
| After application | No intervention | –Forty-nine eyes belonging to 37 patients after injection aPRP. |
| Sham application | Sham comparator | Biological: Platelet rich plasma11 patients before - after aPPP injection |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (4 listed)
- The presence of cataracts or other media opacity that might affect the VF, MP, or mfERG recordings;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Platelet rich plasmablood 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. | Biological | Before application, Sham application |
Primary outcome
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2020.
- Background: PubMed 21268677Koenekoop 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.
- Background: PubMed 22737370Daftarian N, Kiani S, Zahabi A. Regenerative therapy for retinal disorders. J Ophthalmic Vis Res. 2010 Oct;5(4):250-64.
- Background: PubMed 25832910Anitua 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.
- Results publication: PubMed 29546474Arslan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Umut Arslan, MD principal investigator
Ankara Universitesi Teknokent
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Platelet rich plasma in people with Retinitis Pigmentosa, run by Ankara Universitesi Teknokent at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual field sensitivity (time frame: Change from baseline visual field sensitivity at 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04238858, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2020.