Epilepsy (Treatment Refractory)NCT07716930

Retinal OCT Changes and Biomarkers in Drug-Resistant Epilepsy

An observational study of Epilepsy (Treatment Refractory) and Epilepsy, run by Kemal Tutkavul at 1 site in Turkey (Türkiye).

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for: Epilepsy (Treatment Refractory), Epilepsy
How many people: 250 participants
Where: 1 siteTurkey (Türkiye)
Study dates: 1 Jul 2026to Apr 2028
Phase: Observational
Are there results?: Not yet: the study is under way

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 40 years
All sexes
Healthy volunteers accepted
Adult

Study population: The population will consist of three groups: patients with epilepsy (n=150), disease-control patients with chronic pain disorders using relevant medications (n=50) and healthy controls (n=50). Patients with epilepsy will include individuals diagnosed with epilepsy for at least 1 year and treated with at least one antiseizure medication. The epilepsy group will be further categorized according to drug-resistant epilepsy status. Participants with epilepsy will undergo NHS3 and LAEP-TR assessments at baseline and at 18 months using the same standardized administration procedures at both visits. The disease-control group (Control 1 group) will include patients with migraine, analgesic-overuse headache, or neuralgia who have been receiving relevant medication. Healthy controls (Control 2 group; HC) will include volunteers with no history of epilepsy, major neurological disease, ophthalmological disease, or regular antiseizure medication use.

Who may be able to join

Age between 18 and 40 years
Ability to provide written informed consent
For the epilepsy group: diagnosis of epilepsy for at least 1 year
For the epilepsy group: treatment with at least one antiseizure medication for at least 1 year
For the disease-control group: diagnosis of migraine, analgesic-overuse headache, or neuralgia
For the disease-control group: current treatment with at least one antiseizure medication for a non-epileptic indication
For the disease-control group: no history of epilepsy or unprovoked seizures
For the healthy-control group: no history of epilepsy, major neurological disease, ophthalmological disease, or regular antiseizure medication use

Who cannot join

Age younger than 18 years or older than 40 years
Inability or unwillingness to provide written informed consent
History of ocular surgery, ocular trauma, glaucoma, retinal disease, optic neuropathy, or severe refractive error, defined as spherical equivalent greater than ±6.0 diopters
Media opacity or poor image quality preventing reliable OCT or OCTA assessment
Vigabatrin or Valproate use
Multiple sclerosis, Parkinson's disease, dementia, brain tumor, stroke, optic neuritis, or other major neurological disorders

Show all 10Show fewer

Evidence of visual pathway lesions on MRI
Diabetes mellitus, uncontrolled hypertension, or other systemic vascular, metabolic diseases that may affect retinal or OCTA parameters
Chronic alcohol or psychoactive substance abuse
Inability to undergo OCT or OCTA examination because of cognitive, behavioral, or physical limitations

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Turkey (Türkiye)1 site

Saglik Bilimleri University Haydarpasa Numune Education and Research Hospital Neurology Clinic
Istanbul, 34668

Other trials in Turkey (Türkiye)

About this study

Official title: Retina-Based Biomarkers in Epilepsy: Structural and Microvascular OCT Changes and Inflammatory Markers (sCD14, sCD163, CCL2, IL-1β) in Relation to Pathophysiology, Phenotype, Prognosis, and Drug-Resistant Epilepsy (DRE)

This prospective, longitudinal observational study investigates whether epilepsy involves a progressive neurodegenerative process. Retinal structural and microvascular changes assessed by optical coherence tomography (OCT) and optical coherence (OCTA) will be analyzed alongside inflammatory biomarkers (sCD14, sCD163, CCL2, IL-1β). The study aims to explore their association with epilepsy pathophysiology, clinical phenotype, prognosis, and drug-resistant epilepsy (DRE). Among participants with epilepsy, seizure severity and antiseizure medication-related adverse-effect burden will also be assessed longitudinally using the National Hospital Seizure Severity Scale (NHS3) and the Turkish version of Liverpool Adverse Events Profile (LAEP-TR).

Read the detailed description

Epilepsy may be associated with neuroinflammatory and neurodegenerative mechanisms. The retina provides a non-invasive window for evaluating neuroaxonal and microvascular changes through OCT and OCTA. This study will investigate whether retinal structural, microvascular, and serum inflammatory biomarker measures are associated with epilepsy phenotype, disease severity, prognosis, and drug-resistant epilepsy. Participants will be enrolled into three cohorts: adults with epilepsy, adults using antiseizure medications for non-epileptic indications, and healthy controls. Clinical data will include demographic characteristics, epilepsy history, mean monthly seizure frequency derived from seizure diaries and clinical records, antiseizure medication use, neurological examination findings, electroencephalography (EEG) findings, and magnetic resonance imaging (MRI) findings. Among participants with epilepsy, clinical epilepsy activity will be characterized using two prespecified components: mean monthly seizure frequency and seizure severity assessed with the National Hospital Seizure Severity Scale (NHS3). These components will be analyzed separately and jointly in multivariable models rather than combined into a study-specific unvalidated total score. The NHS3 will be administered at baseline and at 18 months based on the participant's most severe habitual seizure during the preceding 6 months. Patient-reported adverse effects associated with antiseizure medication treatment will be assessed separately at the same visits using the Turkish version of Liverpool Adverse Events Profile (LAEP-TR). All participants will undergo ophthalmological assessment, including visual acuity, intraocular pressure measurement, and refraction assessment. OCT and OCTA imaging will be used to measure peripapillary retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, inner nuclear layer thickness, macular volume, hyperreflective retinal foci, capillary density, and foveal avascular zone area.

Peripheral venous blood samples will be collected only from participants in the epilepsy group at baseline and at 18 months for serum biomarker analysis. Serum samples will be stored at -80°C. Serum soluble CD14, soluble CD163, C-C motif chemokine ligand 2, and interleukin-1 beta concentrations will be measured using commercial enzyme-linked immunosorbent assay kits according to the manufacturers' protocols. Serum biomarker outcomes and serum biomarker-based prediction analyses will therefore be restricted to participants with epilepsy.

Conditions: Epilepsy (Treatment Refractory), Epilepsy
Keywords: Drug Resistant Epilepsy, Biomarkers, Neurodegeneration, Neuroinflammation, Optical Coherence Tomography
Medical subject headings: Epilepsy, Drug Resistant Epilepsy, Nerve Degeneration, Neuroinflammatory Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT07716930
Study group	Role	What they receive
Epilepsy Group		Adults (n=150) aged 18 to 40 years with epilepsy for at least 1 year and currently receiving at least one antiseizure medication. Participants in this cohort will complete NHS3 and LAEP-TR assessments at baseline and at 18 months.
Control Group 1		Adults (n=50) aged 18 to 40 years with migraine, medication-overuse headache, or neuralgia who are currently receiving at least one antiseizure medication for a non-epileptic indication and have no history of epilepsy or unprovoked seizures.
Control Group 2(HC)		Healthy volunteers (n=50) aged 18 to 40 years with no known neurological or ophthalmological disease.

What is being measured

The primary outcome is the main question the study is designed to answer.

Annualized percentage change in peripapillary retinal nerve fiber layer thickness measured by OCT
Peripapillary RNFL thickness will be assessed with Heidelberg OCT at baseline and 18 months using the optic nerve head-centered circular scan protocol. Eye-tracking and follow-up registration will ensure reproducibility. Automated segmentation will be reviewed for centration and accuracy; global and quadrant values (superior, inferior, nasal, temporal) will be recorded. Images will be checked for quality and artifacts; scans failing criteria or with uncorrectable errors will be repeated or excluded. For participants with two eligible eyes, mean thickness will be analyzed; if one eye is eligible, that measurement will be used. Annualized percentage change will be calculated as:
[((18-month pRNFL thickness - baseline pRNFL thickness) / baseline pRNFL thickness) × 100] / 1.5 years.
Unit of measure: Percent change per year
Measured: Baseline to 18 months after enrollment.
Annualized percentage change in ganglion cell-inner plexiform layer thickness measured by OCT
Ganglion cell-inner plexiform layer (GC-IPL) thickness will be measured with Heidelberg OCT at baseline and 18 months using a fovea-centered 6 × 6 mm macular scan. Identical parameters and eye-tracking functions will ensure reproducibility. Automated segmentation will be reviewed for centration, accuracy, and artifacts; errors will be corrected when possible. GC-IPL thickness will be calculated as the sum of ganglion cell and inner plexiform layers. Scans failing quality criteria or with uncorrectable artifacts will be repeated or excluded. For two eligible eyes, mean thickness will be analyzed; if one eye is eligible, that measurement will be used. Annualized percentage change will be calculated as:
{[(18-month GC-IPL thickness - baseline GC-IPL thickness) / baseline GC-IPL thickness] × 100} / 1.5 years.
Unit of measure: Percent change per year
Measured: Baseline to 18 months after enrollment
Difference in annualized percentage change in peripapillary retinal nerve fiber layer thickness between drug-resistant and non-drug-resistant epilepsy groups
Annualized percentage change in peripapillary retinal nerve fiber layer thickness measured by optical coherence tomography will be compared between participants with drug-resistant epilepsy and participants without drug-resistant epilepsy. This analysis will be performed only among participants with epilepsy.
Drug-resistant epilepsy will be defined as failure of adequate trials of two tolerated, appropriately chosen and used antiseizure medication schedules to achieve sustained seizure freedom.
Unit of measure: Percent change per year
Measured: Baseline to 18 months after enrollment.
Difference in annualized percentage change in ganglion cell-inner plexiform layer thickness between drug-resistant and non-drug-resistant epilepsy groups
Annualized percentage change in ganglion cell-inner plexiform layer thickness measured by macular optical coherence tomography will be compared between participants with drug-resistant epilepsy and participants without drug-resistant epilepsy. This analysis will be performed only among participants with epilepsy.
Drug-resistant epilepsy will be defined as failure of adequate trials of two tolerated, appropriately chosen and used antiseizure medication schedules to achieve sustained seizure freedom.
Unit of measure: Percent change per year
Measured: Baseline to 18 months after enrollment.

Secondary outcomes (18)

Change in hyperreflective foci count measured on optical coherence tomography
Hyperreflective retinal foci (HRF) will be assessed with Heidelberg OCT at baseline and 18 months using fovea-centered 6 × 6 mm macular scans. Identical parameters will be applied at both visits. HRF will be counted twice per scan volume, and the mean of the two counts will be analyzed. For participants with two eligible eyes, the mean of both eyes will be used; if only one eye is eligible, that measurement will be included. Change will be calculated as the 18-month count minus the baseline count. Unit of measure: Number of hyperreflective foci
Measured: Baseline to 18 months after enrollment.
Difference in hyperreflective retinal foci count between drug-resistant and non-drug-resistant epilepsy groups
Hyperreflective retinal foci count measured on optical coherence tomography will be compared between participants with drug-resistant epilepsy and participants without drug-resistant epilepsy. This analysis will be performed only among participants with epilepsy. Hyperreflective retinal foci will be counted twice on the same scan volume, and the average count will be used for analysis.
Unit of measure: Number of hyperreflective retinal foci
Measured: Baseline to 18 months after enrollment.
Change in superficial macular vessel density measured by optical coherence tomography angiography
Superficial macular vessel density will be measured using optical coherence tomography angiography at baseline and at 18 months. The OCTA device-derived superficial capillary plexus vessel density value will be recorded. The mean value of both eyes will be used for analysis.
Unit of measure: Percentage points
Measured: Baseline to 18 months after enrollment.
Change in deep macular vessel density measured by optical coherence tomography angiography
Deep macular vessel density will be measured using optical coherence tomography angiography at baseline and at 18 months. The OCTA device-derived deep capillary plexus vessel density value will be recorded. The mean value of both eyes will be used for analysis.
Unit of measure: Percentage points
Measured: Baseline to 18 months after enrollment.
Change in peripapillary capillary vessel density measured by optical coherence tomography angiography
Peripapillary capillary vessel density will be measured using optical coherence tomography angiography at baseline and at 18 months. The OCTA device-derived peripapillary capillary density value will be recorded. The mean value of both eyes will be used for analysis.
Unit of measure: Percentage points
Measured: Baseline to 18 months after enrollment.
Change in foveal avascular zone area measured by optical coherence tomography angiography
Foveal avascular zone area will be measured using optical coherence tomography angiography at baseline and at 18 months. The OCTA device-derived foveal avascular zone area will be recorded. The mean value of both eyes will be used for analysis.
Unit of measure: Square millimeters
Measured: Baseline to 18 months after enrollment.
Change from baseline in serum interleukin-1 beta concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy
Serum interleukin-1 beta concentration will be measured only in participants with epilepsy from peripheral venous blood samples collected at baseline and at 18 months. Measurements will be performed using a commercial enzyme-linked immunosorbent assay kit according to the manufacturer's protocol. Change from baseline will be calculated as the 18-month value minus the baseline value.
Unit of measure: Picograms per milliliter(pg/mL)
Measured: Baseline to 18 months after enrollment.
Change from baseline in serum C-C motif chemokine ligand 2 concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy
Serum C-C motif chemokine ligand 2 concentration will be measured only in participants with epilepsy from peripheral venous blood samples collected at baseline and at 18 months. Measurements will be performed using a commercial enzyme-linked immunosorbent assay kit according to the manufacturer's protocol. Change from baseline will be calculated as the 18-month value minus the baseline value.
Unit of Measure: Picograms per milliliter(pg/mL)
Measured: Baseline to 18 months after enrollment.
Change from baseline in serum soluble CD14 concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy
Serum soluble CD14 concentration will be measured only in participants with epilepsy from peripheral venous blood samples collected at baseline and at 18 months. Measurements will be performed using a commercial enzyme-linked immunosorbent assay kit according to the manufacturer's protocol. Change from baseline will be calculated as the 18-month value minus the baseline value.
Unit of measure: Nanograms per milliliter(ng/mL)
Measured: Baseline to 18 months after enrollment.
Change from baseline in serum soluble CD163 concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy
Serum soluble CD163 concentration will be measured only in participants with epilepsy from peripheral venous blood samples collected at baseline and at 18 months. Measurements will be performed using a commercial enzyme-linked immunosorbent assay kit according to the manufacturer's protocol. Change from baseline will be calculated as the 18-month value minus the baseline value.
Unit of measure: Nanograms per milliliter(ng/mL)
Measured: Baseline to 18 months after enrollment.
Association of mean monthly seizure frequency and baseline National Hospital Seizure Severity Scale score with annualized percentage change in peripapillary retinal nerve fiber layer thickness
Among participants with epilepsy, mean monthly seizure frequency during follow-up will be calculated from seizure diaries and clinical records. Baseline seizure severity will be assessed with the National Hospital Seizure Severity Scale (NHS3), based on all seizure types experienced in the past 6 months and their severity. Annualized percentage change in peripapillary RNFL thickness will be derived from baseline and 18-month OCT measurements. Independent associations of seizure frequency and NHS3 total score with RNFL change will be evaluated using multivariable linear regression.
Unit of Measure: Regression coefficient
Measured: Baseline to 18 months after enrollment.
Association of mean monthly seizure frequency and baseline National Hospital Seizure Severity Scale score with annualized percentage change in ganglion cell-inner plexiform layer thickness
Among participants with epilepsy, mean monthly seizure frequency during follow-up will be calculated from seizure diaries and clinical records. Baseline seizure severity will be assessed with the National Hospital Seizure Severity Scale (NHS3), based on all seizure types experienced in the past 6 months and their severity. Annualized percentage change in ganglion cell-inner plexiform layer (GC-IPL) thickness will be derived from baseline and 18-month OCT measurements. Independent associations of seizure frequency and NHS3 total score with GC-IPL change will be evaluated using multivariable linear regression. Unit of Measure: Regression coefficient
Measured: Baseline to 18 months after enrollment.
Correlation between number of antiseizure medications and ganglion cell-inner plexiform layer thickness measured by optical coherence tomography
The number of antiseizure medications will be recorded from clinical records. Ganglion cell-inner plexiform layer thickness will be measured using macular optical coherence tomography. The correlation between the number of antiseizure medications and ganglion cell-inner plexiform layer thickness will be assessed using Pearson or Spearman correlation according to data distribution.
Unit of Measure: Correlation coefficient
Measured: Baseline to 18 months after enrollment.
Difference in peripapillary retinal nerve fiber layer thickness across epilepsy syndrome groups
Peripapillary retinal nerve fiber layer thickness measured by optical coherence tomography will be compared across epilepsy syndrome groups classified according to the International League Against Epilepsy classification. The mean value of both eyes will be used for analysis.
Unit of Measure: Micrometers(µm)
Measured: Baseline to 18 months after enrollment.
Difference in ganglion cell-inner plexiform layer thickness across epilepsy syndrome groups
Ganglion cell-inner plexiform layer thickness measured by macular optical coherence tomography will be compared across epilepsy syndrome groups classified according to the International League Against Epilepsy classification. The mean value of both eyes will be used for analysis.
Unit of Measure: Micrometers(µm)
Measured: Baseline to 18 months after enrollment.
Predictive performance of a predefined retinal-inflammatory biomarker model for drug-resistant epilepsy status
A predefined multivariable prediction model will include retinal structural measures, optical coherence tomography angiography-derived vascular measures, hyperreflective retinal foci count, and serum inflammatory biomarker concentrations. The model's ability to predict drug-resistant epilepsy status will be evaluated using the area under the receiver operating characteristic curve.
Unit of Measure: Area under the receiver operating characteristic curve
Measured: Baseline to 18 months after enrollment.
Change from baseline in National Hospital Seizure Severity Scale score among participants with epilepsy
The National Hospital Seizure Severity Scale (NHS3) will be administered to participants with epilepsy at baseline and 18 months. All seizure types experienced in the past 6 months and their severity will be evaluated, applying the same predefined seizure-selection rule at both visits. Change from baseline will be calculated as the 18-month NHS3 total score minus the baseline score.
Unit of Measure: Points.
Measured: Baseline to 18 months after enrollment
Change from baseline in Turkish version of Liverpool Adverse Events Profile total score among participants with epilepsy
The Turkish version of Liverpool Adverse Events Profile (LAEP-TR) will be administered to participants with epilepsy at baseline and 18 months to assess patient-reported adverse effects of antiseizure medications. Change from baseline will be calculated as the 18-month LAEP-TR total score minus the baseline score.
Unit of Measure: Points.
Measured: Baseline to 18 months after enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jul 2026Apr 2028

First posted21 Jul 2026
Study start1 Jul 2026
Primary completionJan 2028 (estimated)
Study completionApr 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (21)Papers the sponsor has linked to this study.
Other trials for Epilepsy (Treatment Refractory)Studies 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: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 250 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07716930
Sponsor's protocol ID: 2024-KAEK-18/2026/10
Other IDs: 55435
Status last verified: Jul 2026
First submitted: 26 Jun 2026
Last updated: 21 Jul 2026
Results posted: No
Data monitoring committee: No
Individual data sharing: Yes: All IPD that underlie results in a publication

Publications

Mermi-Dibek D, Kılıç B, Oztura İ, Baklan B. The liverpool adverse drug events profile (LAEP): Validity and reliability of Turkish version (LAEP-TR). Neurol Sci Neurophysiol 2023;40:101-5. DOI: 10.4103/nsn.nsn_83_23
O'Donoghue MF, Duncan JS, Sander JW. The National Hospital Seizure Severity Scale: a further development of the Chalfont Seizure Severity Scale. Epilepsia. 1996 Jun;37(6):563-71. doi: 10.1111/j.1528-1157.1996.tb00610.x.
PubMed 8641234
Aguilar-Castillo MJ, Estivill-Torrus G, Garcia-Martin G, Cabezudo-Garcia P, Lopez-Moreno Y, Ortega-Pinazo J, Ramirez-Garcia T, Ciano-Petersen NL, Serrano-Castro PJ. Inflammatory Drug-Resistant Epilepsy Index (IDREI) as a Molecular Compound Biomarker in Focal Epilepsies. Biomolecules. 2025 Jun 22;15(7):914. doi: 10.3390/biom15070914.
PubMed 40723787
Rider F, Guekht A, Shpak A. Optical coherence tomography angiography in patients with focal epilepsy. Front Neurol. 2025 Jan 29;16:1529409. doi: 10.3389/fneur.2025.1529409. eCollection 2025.
PubMed 39944552
Ahl M, Avdic U, Skoug C, Ali I, Chugh D, Johansson UE, Ekdahl CT. Immune response in the eye following epileptic seizures. J Neuroinflammation. 2016 Jun 27;13(1):155. doi: 10.1186/s12974-016-0618-3.
PubMed 27346214
Pilotto E, Torresin T, Bacelle ML, De Moja G, Ferrara AM, Zovato S, Midena G, Midena E. Hyper-reflective retinal foci as possible in vivo imaging biomarker of microglia activation in von Hippel-Lindau disease. PLoS One. 2022 Aug 12;17(8):e0272318. doi: 10.1371/journal.pone.0272318. eCollection 2022.
PubMed 35960779
Midena E, Torresin T, Velotta E, Pilotto E, Parrozzani R, Frizziero L. OCT Hyperreflective Retinal Foci in Diabetic Retinopathy: A Semi-Automatic Detection Comparative Study. Front Immunol. 2021 Apr 22;12:613051. doi: 10.3389/fimmu.2021.613051. eCollection 2021.
PubMed 33968016
Cherkezzade M, Soylu S, Tuzun E, Yilmaz V, Sezgin M, Yapici Z, Kucukali CI, Topaloglu P. The Association Between Serum Levels of Glial Biomarkers, Clinical Severity and Electro-encephalography Features in Idiopathic West and Lennox-Gastaut Syndromes. Noro Psikiyatr Ars. 2024 Feb 2;61(2):128-134. doi: 10.29399/npa.28669. eCollection 2024.
PubMed 38868840
Pranzatelli MR, Tate ED, McGee NR. Microglial/macrophage markers CHI3L1, sCD14, and sCD163 in CSF and serum of pediatric inflammatory and non-inflammatory neurological disorders: A case-control study and reference ranges. J Neurol Sci. 2017 Oct 15;381:285-290. doi: 10.1016/j.jns.2017.09.006. Epub 2017 Sep 6.
PubMed 28991699
Stilund M, Reuschlein AK, Christensen T, Moller HJ, Rasmussen PV, Petersen T. Soluble CD163 as a marker of macrophage activity in newly diagnosed patients with multiple sclerosis. PLoS One. 2014 Jun 2;9(6):e98588. doi: 10.1371/journal.pone.0098588. eCollection 2014.
PubMed 24886843
Tan TH, Sequeira RP, Perucca P, Kwan P, O'Brien TJ, Monif M. Peripheral cytokine and monocyte phenotype associations in drug-resistant epilepsy. Sci Rep. 2025 Aug 13;15(1):29654. doi: 10.1038/s41598-025-14402-4.
PubMed 40804444
Milano C, Montali M, Barachini S, Burzi IS, Pratesi F, Petrozzi L, Chico L, Morganti R, Gambino G, Rossi L, Ceravolo R, Siciliano G, Migliorini P, Petrini I, Pizzanelli C. Increased production of inflammatory cytokines by circulating monocytes in mesial temporal lobe epilepsy: A possible role in drug resistance. J Neuroimmunol. 2024 Jan 15;386:578272. doi: 10.1016/j.jneuroim.2023.578272. Epub 2023 Dec 23.
PubMed 38160122
Ceska K, Papez J, Oslejskova H, Slaby O, Radova L, Loja T, Liba Z, Sverakova A, Brazdil M, Aulicka S. CCL2/MCP-1, interleukin-8, and fractalkine/CXC3CL1: Potential biomarkers of epileptogenesis and pharmacoresistance in childhood epilepsy. Eur J Paediatr Neurol. 2023 Sep;46:48-54. doi: 10.1016/j.ejpn.2023.06.001. Epub 2023 Jun 15.
PubMed 37429062
Stauner L, Bao H, Delazer L, Kirsch I, Christmann T, Noachtar S, Havla J, Lauseker M, Kaufmann E. Longitudinal evaluation of retinal neuroaxonal loss in epilepsy using optical coherence tomography. Epilepsia. 2024 Dec;65(12):3644-3654. doi: 10.1111/epi.18139. Epub 2024 Oct 9.
PubMed 39380535
Clayton LM, Devile M, Punte T, de Haan GJ, Sander JW, Acheson JF, Sisodiya SM. Patterns of peripapillary retinal nerve fiber layer thinning in vigabatrin-exposed individuals. Ophthalmology. 2012 Oct;119(10):2152-60. doi: 10.1016/j.ophtha.2012.05.009. Epub 2012 Jul 30.
PubMed 22853973

Interested in taking part?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
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Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Retina-Based Biomarkers in Epilepsy: Structural and Microvascular OCT Changes and Inflammatory Markers (sCD14, sCD163, CCL2, IL-1β) in Relation to Pathophysiology, Phenotype, Prognosis, and Drug-Resistant Epilepsy (DRE)
ClinicalTrials.gov ID: NCT07716930
Acronym / sponsor ID: 2024-KAEK-18/2026/10
Conditions: Epilepsy (Treatment Refractory), Epilepsy
Keywords: Drug Resistant Epilepsy, Biomarkers, Neurodegeneration, Neuroinflammation, Optical Coherence Tomography
Study type: Observational
Recruitment status: Enrolling by invitation
Enrolment: 250 participants (estimated)
Lead sponsor: Kemal TutkavulUniversity, hospital or other
Collaborators: Haydarpasa Numune Training and Research Hospital Department of Neurology, Haydarpasa Numune Training and Research Hospital Department of Ophthalmology, Istanbul University Aziz Sancar Institute of Experimental Medicine, Health Institutes of Türkiye
Study start: 1 Jul 2026 (actual)
Primary completion: Jan 2028 (estimated)
Study completion: Apr 2028 (estimated)
First posted: 21 Jul 2026 (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.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 3

Arm	Type	Receives
Epilepsy Group	–	–Adults (n=150) aged 18 to 40 years with epilepsy for at least 1 year and currently receiving at least one antiseizure medication. Participants in this cohort will complete NHS3 and LAEP-TR assessments at baseline and at 18 months.
Control Group 1	–	–Adults (n=50) aged 18 to 40 years with migraine, medication-overuse headache, or neuralgia who are currently receiving at least one antiseizure medication for a non-epileptic indication and have no history of epilepsy or unprovoked seizures.
Control Group 2(HC)	–	–Healthy volunteers (n=50) aged 18 to 40 years with no known neurological or ophthalmological disease.

Who may qualify

Ages: 18 to 40 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult
Study population: The population will consist of three groups: patients with epilepsy (n=150), disease-control patients with chronic pain disorders using relevant medications (n=50) and healthy controls (n=50). Patients with epilepsy will include individuals diagnosed with epilepsy for at least 1 year and treated with at least one antiseizure medication. The epilepsy group will be further categorized according to drug-resistant epilepsy status. Participants with epilepsy will undergo NHS3 and LAEP-TR assessments at baseline and at 18 months using the same standardized administration procedures at both visits. The disease-control group (Control 1 group) will include patients with migraine, analgesic-overuse headache, or neuralgia who have been receiving relevant medication. Healthy controls (Control 2 group; HC) will include volunteers with no history of epilepsy, major neurological disease, ophthalmological disease, or regular antiseizure medication use.

Key inclusion criteria (8 listed)

Age between 18 and 40 years
Ability to provide written informed consent
For the epilepsy group: diagnosis of epilepsy for at least 1 year
For the epilepsy group: treatment with at least one antiseizure medication for at least 1 year
For the disease-control group: diagnosis of migraine, analgesic-overuse headache, or neuralgia

Key exclusion criteria (10 listed)

Age younger than 18 years or older than 40 years
Inability or unwillingness to provide written informed consent
History of ocular surgery, ocular trauma, glaucoma, retinal disease, optic neuropathy, or severe refractive error, defined as spherical equivalent greater than ±6.0 diopters
Media opacity or poor image quality preventing reliable OCT or OCTA assessment
Vigabatrin or Valproate use

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

Annualized percentage change in peripapillary retinal nerve fiber layer thickness measured by OCT
Time frame: Baseline to 18 months after enrollment.
Peripapillary RNFL thickness will be assessed with Heidelberg OCT at baseline and 18 months using the optic nerve head-centered circular scan protocol. Eye-tracking and follow-up registration will ensure reproducibility. Automated segmentation will be reviewed for centration and accuracy; global and quadrant values (superior, inferior, nasal, temporal) will be recorded. Images will be checked for quality and artifacts; scans failing criteria or with uncorrectable errors will be repeated or excluded. For participants with two eligible eyes, mean thickness will be analyzed; if one eye is eligible, that measurement will be used. Annualized percentage change will be calculated as: [((18-month pRNFL thickness - baseline pRNFL thickness) / baseline pRNFL thickness) × 100] / 1.5 years. Unit of measure: Percent change per year
Annualized percentage change in ganglion cell-inner plexiform layer thickness measured by OCT
Time frame: Baseline to 18 months after enrollment
Ganglion cell-inner plexiform layer (GC-IPL) thickness will be measured with Heidelberg OCT at baseline and 18 months using a fovea-centered 6 × 6 mm macular scan. Identical parameters and eye-tracking functions will ensure reproducibility. Automated segmentation will be reviewed for centration, accuracy, and artifacts; errors will be corrected when possible. GC-IPL thickness will be calculated as the sum of ganglion cell and inner plexiform layers. Scans failing quality criteria or with uncorrectable artifacts will be repeated or excluded. For two eligible eyes, mean thickness will be analyzed; if one eye is eligible, that measurement will be used. Annualized percentage change will be calculated as: {[(18-month GC-IPL thickness - baseline GC-IPL thickness) / baseline GC-IPL thickness] × 100} / 1.5 years. Unit of measure: Percent change per year
Difference in annualized percentage change in peripapillary retinal nerve fiber layer thickness between drug-resistant and non-drug-resistant epilepsy groups
Time frame: Baseline to 18 months after enrollment.
Annualized percentage change in peripapillary retinal nerve fiber layer thickness measured by optical coherence tomography will be compared between participants with drug-resistant epilepsy and participants without drug-resistant epilepsy. This analysis will be performed only among participants with epilepsy. Drug-resistant epilepsy will be defined as failure of adequate trials of two tolerated, appropriately chosen and used antiseizure medication schedules to achieve sustained seizure freedom. Unit of measure: Percent change per year
Difference in annualized percentage change in ganglion cell-inner plexiform layer thickness between drug-resistant and non-drug-resistant epilepsy groups
Time frame: Baseline to 18 months after enrollment.
Annualized percentage change in ganglion cell-inner plexiform layer thickness measured by macular optical coherence tomography will be compared between participants with drug-resistant epilepsy and participants without drug-resistant epilepsy. This analysis will be performed only among participants with epilepsy. Drug-resistant epilepsy will be defined as failure of adequate trials of two tolerated, appropriately chosen and used antiseizure medication schedules to achieve sustained seizure freedom. Unit of measure: Percent change per year

18 secondary outcomes

Change in hyperreflective foci count measured on optical coherence tomography
Time frame: Baseline to 18 months after enrollment.
Difference in hyperreflective retinal foci count between drug-resistant and non-drug-resistant epilepsy groups
Time frame: Baseline to 18 months after enrollment.
Change in superficial macular vessel density measured by optical coherence tomography angiography
Time frame: Baseline to 18 months after enrollment.
Change in deep macular vessel density measured by optical coherence tomography angiography
Time frame: Baseline to 18 months after enrollment.
Change in peripapillary capillary vessel density measured by optical coherence tomography angiography
Time frame: Baseline to 18 months after enrollment.
Change in foveal avascular zone area measured by optical coherence tomography angiography
Time frame: Baseline to 18 months after enrollment.
Change from baseline in serum interleukin-1 beta concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy
Time frame: Baseline to 18 months after enrollment.
Change from baseline in serum C-C motif chemokine ligand 2 concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy
Time frame: Baseline to 18 months after enrollment.
Change from baseline in serum soluble CD14 concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy
Time frame: Baseline to 18 months after enrollment.
Change from baseline in serum soluble CD163 concentration measured by enzyme-linked immunosorbent assay in participants with epilepsy
Time frame: Baseline to 18 months after enrollment.
Association of mean monthly seizure frequency and baseline National Hospital Seizure Severity Scale score with annualized percentage change in peripapillary retinal nerve fiber layer thickness
Time frame: Baseline to 18 months after enrollment.
Association of mean monthly seizure frequency and baseline National Hospital Seizure Severity Scale score with annualized percentage change in ganglion cell-inner plexiform layer thickness
Time frame: Baseline to 18 months after enrollment.
Correlation between number of antiseizure medications and ganglion cell-inner plexiform layer thickness measured by optical coherence tomography
Time frame: Baseline to 18 months after enrollment.
Difference in peripapillary retinal nerve fiber layer thickness across epilepsy syndrome groups
Time frame: Baseline to 18 months after enrollment.
Difference in ganglion cell-inner plexiform layer thickness across epilepsy syndrome groups
Time frame: Baseline to 18 months after enrollment.
Predictive performance of a predefined retinal-inflammatory biomarker model for drug-resistant epilepsy status
Time frame: Baseline to 18 months after enrollment.
Change from baseline in National Hospital Seizure Severity Scale score among participants with epilepsy
Time frame: Baseline to 18 months after enrollment
Change from baseline in Turkish version of Liverpool Adverse Events Profile total score among participants with epilepsy
Time frame: Baseline to 18 months after enrollment

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
Results publicationMermi-Dibek D, Kılıç B, Oztura İ, Baklan B. The liverpool adverse drug events profile (LAEP): Validity and reliability of Turkish version (LAEP-TR). Neurol Sci Neurophysiol 2023;40:101-5. DOI: 10.4103/nsn.nsn_83_23
Results publication: PubMed 8641234O'Donoghue MF, Duncan JS, Sander JW. The National Hospital Seizure Severity Scale: a further development of the Chalfont Seizure Severity Scale. Epilepsia. 1996 Jun;37(6):563-71. doi: 10.1111/j.1528-1157.1996.tb00610.x.
Results publication: PubMed 40723787Aguilar-Castillo MJ, Estivill-Torrus G, Garcia-Martin G, Cabezudo-Garcia P, Lopez-Moreno Y, Ortega-Pinazo J, Ramirez-Garcia T, Ciano-Petersen NL, Serrano-Castro PJ. Inflammatory Drug-Resistant Epilepsy Index (IDREI) as a Molecular Compound Biomarker in Focal Epilepsies. Biomolecules. 2025 Jun 22;15(7):914. doi: 10.3390/biom15070914.
Results publication: PubMed 39944552Rider F, Guekht A, Shpak A. Optical coherence tomography angiography in patients with focal epilepsy. Front Neurol. 2025 Jan 29;16:1529409. doi: 10.3389/fneur.2025.1529409. eCollection 2025.
Results publication: PubMed 27346214Ahl M, Avdic U, Skoug C, Ali I, Chugh D, Johansson UE, Ekdahl CT. Immune response in the eye following epileptic seizures. J Neuroinflammation. 2016 Jun 27;13(1):155. doi: 10.1186/s12974-016-0618-3.
Results publication: PubMed 35960779Pilotto E, Torresin T, Bacelle ML, De Moja G, Ferrara AM, Zovato S, Midena G, Midena E. Hyper-reflective retinal foci as possible in vivo imaging biomarker of microglia activation in von Hippel-Lindau disease. PLoS One. 2022 Aug 12;17(8):e0272318. doi: 10.1371/journal.pone.0272318. eCollection 2022.
Results publication: PubMed 33968016Midena E, Torresin T, Velotta E, Pilotto E, Parrozzani R, Frizziero L. OCT Hyperreflective Retinal Foci in Diabetic Retinopathy: A Semi-Automatic Detection Comparative Study. Front Immunol. 2021 Apr 22;12:613051. doi: 10.3389/fimmu.2021.613051. eCollection 2021.
Results publication: PubMed 38868840Cherkezzade M, Soylu S, Tuzun E, Yilmaz V, Sezgin M, Yapici Z, Kucukali CI, Topaloglu P. The Association Between Serum Levels of Glial Biomarkers, Clinical Severity and Electro-encephalography Features in Idiopathic West and Lennox-Gastaut Syndromes. Noro Psikiyatr Ars. 2024 Feb 2;61(2):128-134. doi: 10.29399/npa.28669. eCollection 2024.
Results publication: PubMed 28991699Pranzatelli MR, Tate ED, McGee NR. Microglial/macrophage markers CHI3L1, sCD14, and sCD163 in CSF and serum of pediatric inflammatory and non-inflammatory neurological disorders: A case-control study and reference ranges. J Neurol Sci. 2017 Oct 15;381:285-290. doi: 10.1016/j.jns.2017.09.006. Epub 2017 Sep 6.
Results publication: PubMed 24886843Stilund M, Reuschlein AK, Christensen T, Moller HJ, Rasmussen PV, Petersen T. Soluble CD163 as a marker of macrophage activity in newly diagnosed patients with multiple sclerosis. PLoS One. 2014 Jun 2;9(6):e98588. doi: 10.1371/journal.pone.0098588. eCollection 2014.
Results publication: PubMed 40804444Tan TH, Sequeira RP, Perucca P, Kwan P, O'Brien TJ, Monif M. Peripheral cytokine and monocyte phenotype associations in drug-resistant epilepsy. Sci Rep. 2025 Aug 13;15(1):29654. doi: 10.1038/s41598-025-14402-4.
Results publication: PubMed 38160122Milano C, Montali M, Barachini S, Burzi IS, Pratesi F, Petrozzi L, Chico L, Morganti R, Gambino G, Rossi L, Ceravolo R, Siciliano G, Migliorini P, Petrini I, Pizzanelli C. Increased production of inflammatory cytokines by circulating monocytes in mesial temporal lobe epilepsy: A possible role in drug resistance. J Neuroimmunol. 2024 Jan 15;386:578272. doi: 10.1016/j.jneuroim.2023.578272. Epub 2023 Dec 23.
Individual participant dataSharing planned: Yes. All IPD that underlie results in a publication

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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.

KEMAL TUTKAVUL, Professor study director

Saglik Bilimleri University Haydarpasa Numune Education and Research Hospital Neurology Clinic

NUR D BASPINAR, MD principal investigator

Saglik Bilimleri University Haydarpasa Numune Education and Research Hospital Neurology Clinic

ECE TURAN VARDAR, Professor study director

Saglik Bilimleri University Haydarpasa Numune Education and Research Hospital Ophthalmology Clinic

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Epilepsy (Treatment Refractory) and Epilepsy, run by Kemal Tutkavul 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 8 inclusion and 10 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: enrolling by invitation, as of the sponsor's last update on 21 Jul 2026. 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. 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?

This study is still under way. Results are not available in the source record yet.

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?

Annualized percentage change in peripapillary retinal nerve fiber layer thickness measured by OCT (time frame: Baseline to 18 months after enrollment.). The study lists 4 primary outcomes in all. 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 NCT07716930, which also lists 21 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 21 Jul 2026.