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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).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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

Other trials in Turkey (Türkiye)

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.

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 groups in NCT04238858
Study groupRoleWhat they receive
Before applicationActive comparatorForty-nine eyes belonging to 37 patients before injection aPRP.
Receives: Biological: Platelet rich plasma
After applicationNo interventionForty-nine eyes belonging to 37 patients after injection aPRP.
Sham applicationSham comparator11 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.

  1. 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.

  1. First posted23 Jan 2020
  2. Study start1 Sep 2016
  3. Primary completion28 Feb 2017
  4. Study completion30 Jan 2018

Resources

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)
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 21268677
  • Daftarian N, Kiani S, Zahabi A. Regenerative therapy for retinal disorders. J Ophthalmic Vis Res. 2010 Oct;5(4):250-64.

    PubMed 22737370
  • 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.

    PubMed 25832910
  • 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.

    PubMed 29546474

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.

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