Diabetic Macular EdemaPhase 4FORESIGHTNCT03780361
Changes in Inflammatory Biomarkers Including Soluble CD14 and Hyperreflective Foci in DME Patients Treated With Aflibercept (FORESIGHT)
A Phase 4 study testing Aflibercept Injection in people with Diabetic Macular Edema, run by Hyewon Chung at 1 site in South Korea.
Trial summary
This study evaluates the effect of aflibercept on the change of cytokines incluing sCD14, MCP-1, IL-6, and ICAM-1 in the aqueous humor of DME patients. Additionally, changes of visual acuity (ETDRS), optical coherence tomography parameters including hyperreflective foci and thickness of macula are also investigated. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Diabetic Macular Edema
- What is being tested?
- Aflibercept Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteSouth Korea
- Study dates
- 17 May 2019to 1 Feb 2024
- Phase
- Phase 4
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥ 19 years with type 1 or 2 diabetes mellitus.
- Patients with DME secondary to diabetes mellitus involving the center of the macula (defined as the OCT center subfield) in the study eye.
- Decrease in vision determined to be primarily the result of DME in the study eye.
- BCVA ETDRS letter score of 80 to 24 (20/25 to 20/320) in the study eye.
- Retinal thickness ≥ 300 µm as assessed by OCT in the study eye.
- Willing and able to comply with clinic visits and study-related procedures.
Who cannot join
- Ocular conditions with a poorer prognosis in the fellow eye than in the study eye.
- History of vitreoretinal surgery in the study eye.
- Previous treatment with intraocular anti-angiogenic drugs (bevacizumab, ranibizumab etc.) or laser photocoagulation in the study eye within 90 days.
- Previous use of intraocular or periocular corticosteroids in the study eye within 120 days of day 1.
- Invasive intraocular surgery incluing cataract surgery within 90 days of day 1.
- Yttrium-aluminium-garnet capsulotomy in the study eye within 30 days before day 1.
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- Aphakia in the study eye.
- Vitreomacular traction or epiretinal membrane in the study eye evident on OCT that is thought to affect central vision.
- Active proliferative diabetic retinopathy in the study eye.
- Current iris neovascularization in the study eye.
- Evidence of infection including infectious blepharitis, keratitis, scleritis, conjunctivitis or endophthalmitis in either eye.
- Uncontrolled glaucoma in the study eye or filtration surgery for glaucoma in the past or likely to be needed in the future on the study eye.
- Intraocular pressure ≥25 mmHg in the study eye.
- Myopia of a spherical equivalent prior to any possible refractive or cataract surgery of ≥ -8 diopters.
- Concurrent disease in the study eye, other than DME, that could compromise VA, require medical or surgical intervention during the study period, or could confound interpretation of the results (including uveitis, retinal vascular occlusion, retinal detachment, macular hole, significanlty large hard exudate at macula, atrophy of retinal pigment epithelium, submacular scar, macular isdhemia, or choroidal neovascularization).
- Only one functional eye even if that eye is otherwise eligible for the study.
- Ocular media of insufficient quality to obtain fundus and OCT images.
- Current treatment for a serious systemic infection.
- Administration of systemic anti-angiogenic agents within 180 days before day 1.
- Pregnant women, pregnancy planning during the study period, lactating
- Severe active intraocular inflammation is observed in the eyes injected with Aflibercept
- History of hypersensitivity to Aflibercept or excipient
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Changes in Inflammatory Biomarkers Including Soluble CD14 and Hyperreflective Foci in Diabetic Macular Edema Patients Treated With Aflibercept (FORESIGHT)
This study evaluates the effect of aflibercept on the change of cytokines incluing sCD14, MCP-1, IL-6, and ICAM-1 in the aqueous humor of DME patients. Additionally, changes of visual acuity (ETDRS), optical coherence tomography parameters including hyperreflective foci and thickness of macula are also investigated.
Read the detailed description
Intraocular steroid agents have been shown to decrease inflammatory cytokines in diabetic macular edema (DME) patients and thus have roles in the treatment of these patients. However, I believe that anti-VEGF could effectively decrease intraocular inflammatory responses in these patients with much fewer side effects than intraocular steroid agents.
Since soluble CD14 (sCD14) is the known marker of inflammatory cells including microglia, increased or decreased retinal inflammation accompanied by DME could be monitored using sCD14 in patients with DME. Recently, I published an article regarding the strong association of increased sCD14 in the aqueous humor (AH) from DME patients, especially in increased inner retinal edema as well as increased hyper reflective foci (HF) in optical coherence tomography (OCT). This associated changes of sCD14 levels and HF in the retina suggested that the HF might represent the activated microglia in DME. I also showed that the intravitreal bevacizumab injection resulted in a reduction of sCD14 in the AH and HF in OCT. However, that study was retrospective and I could not have many patients' follow-up data after bevacizumab treatments and thus was not able to get conclusive results regarding decreased retinal inflammation after anti-VEGF. Therefore, I believe that a well-desinged prospective study is needed to clarify whether retinal inflammation is ameliorated after anti-VEGF treatment. Moreover, I believe that aflibercept is more appropriate and better drug than bevacizumab to investigate the changes in the cytokine levels along with the improvement of inflammatory milieu in DME due to the following reasons. First, recent DRCR.net Protocol-T reported the superior clinical outome of aflibercept compared to bevacizumab on DME. Second, aflibercept has significantly higher binding affinity to VEGF-A compared to ranibizumab or bevacizumab. Third, aflibercept also binds to VEGF-B and placental growth factor (PlGF), unlike ranibizumab or bevacizumab. PlGF-VEGFR1 pathway contributes to inflammation by triggering production of proinflammatory cytokines.
Thus, I would like to investigate the efficacy of aflibercept for reducing inflammation in DME. Therapeutic effects of aflibercept on reduction of DME in the context of amelioration of inflammation will be proved using sCD14 and HF as surrogate markers in this proposed study. Besides sCD14, tracking the cytokines including MCP-1, IL-6, and ICAM-1 in the AH in a well-controlled prospective setting of aflibercept treatments will enhance our understanding regarding the role of inflammation on DME, and the importance of aflibercept for decreasing ocular inflammation in DME patients.
- Conditions
- Diabetic Macular Edema
- Being tested
- Aflibercept Injection
- Keywords
- soluble CD14, MCP-1, IL-6, ICAM-1, cytokine, visual acuity, optical coherence tomography, macular thickness, hyperreflective foci
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aflibercept InjectionDrug
Also called Eylea
Total 5 times of monthly intravitreal aflibercept injections will be done.
| Study group | Role | What they receive |
|---|---|---|
| Aflibercept injection group | Experimental | drug: Eylea (aflibercept) (11.12mg/0.278ml) dose: 2mg (0.05ml) usage: With topical anesthesia and intravitreal injection of aflibercpt in aseptic condition.
frequency and duration: monthly intravitreal aflibercept injections. Receives: Drug: Aflibercept Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the level of sCD14 in the aqueous humor
Change in the level of sCD14 in the aqueous humor measured by ELISA
Measured: From baseline to week 20
Secondary outcomes (4)
Change in the levels of cytokines (MCP-1, IL-6, ICAM-1) in the aqueous humor
Change in the levels of cytokines (MCP-1, IL-6, ICAM-1) in the aqueous humor measured by ELISA
Measured: From baseline to week 20
Change in the number of hyperreflective foci (HF) on optical coherence tomography (OCT)
Change in the number of HF on optical coherence tomography OCT B-scan
Measured: From baseline to week 20
Change in the thickeness of macula on OCT
Change in the thickeness of macula on OCT
Measured: From baseline to week 20
Change in mean visual acuity (ETDRS)
Change in mean visual acuity (ETDRS)
Measured: From baseline to week 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2018
- Study start17 May 2019
- Primary completion1 Jan 2023
- Study completion1 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic Macular EdemaStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hyewon Chung
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor-investigator, Hyewon Chung, Konkuk University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03780361
- Sponsor's protocol ID
- 20658
- Acronym
- FORESIGHT
- Status last verified
- May 2024
- First submitted
- 17 Dec 2018
- Last updated
- 29 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lee H, Jang H, Choi YA, Kim HC, Chung H. Association Between Soluble CD14 in the Aqueous Humor and Hyperreflective Foci on Optical Coherence Tomography in Patients With Diabetic Macular Edema. Invest Ophthalmol Vis Sci. 2018 Feb 1;59(2):715-721. doi: 10.1167/iovs.17-23042.
PubMed 29392317
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Changes in Inflammatory Biomarkers Including Soluble CD14 and Hyperreflective Foci in Diabetic Macular Edema Patients Treated With Aflibercept (FORESIGHT)
- ClinicalTrials.gov ID
- NCT03780361
- Acronym / sponsor ID
- FORESIGHT / 20658
- Conditions
- Diabetic Macular Edema
- Keywords
- soluble CD14, MCP-1, IL-6, ICAM-1, cytokine, visual acuity, optical coherence tomography, macular thickness
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Hyewon ChungUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- 17 May 2019 (actual)
- Primary completion
- 1 Jan 2023 (actual)
- Study completion
- 1 Feb 2024 (actual)
- First posted
- 19 Dec 2018 (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.
This study evaluates the effect of aflibercept on the change of cytokines incluing sCD14, MCP-1, IL-6, and ICAM-1 in the aqueous humor of DME patients. Additionally, changes of visual acuity (ETDRS), optical coherence tomography parameters including hyperreflective foci and thickness of macula are also investigated.
Detailed description
Intraocular steroid agents have been shown to decrease inflammatory cytokines in diabetic macular edema (DME) patients and thus have roles in the treatment of these patients. However, I believe that anti-VEGF could effectively decrease intraocular inflammatory responses in these patients with much fewer side effects than intraocular steroid agents.
Since soluble CD14 (sCD14) is the known marker of inflammatory cells including microglia, increased or decreased retinal inflammation accompanied by DME could be monitored using sCD14 in patients with DME. Recently, I published an article regarding the strong association of increased sCD14 in the aqueous humor (AH) from DME patients, especially in increased inner retinal edema as well as increased hyper reflective foci (HF) in optical coherence tomography (OCT). This associated changes of sCD14 levels and HF in the retina suggested that the HF might represent the activated microglia in DME. I also showed that the intravitreal bevacizumab injection resulted in a reduction of sCD14 in the AH and HF in OCT. However, that study was retrospective and I could not have many patients' follow-up data after bevacizumab treatments and thus was not able to get conclusive results regarding decreased retinal inflammation after anti-VEGF. Therefore, I believe that a well-desinged prospective study is needed to clarify whether retinal inflammation is ameliorated after anti-VEGF treatment. Moreover, I believe that aflibercept is more appropriate and better drug than bevacizumab to investigate the changes in the cytokine levels along with the improvement of inflammatory milieu in DME due to the following reasons. First, recent DRCR.net Protocol-T reported the superior clinical outome of aflibercept compared to bevacizumab on DME. Second, aflibercept has significantly higher binding affinity to VEGF-A compared to ranibizumab or bevacizumab. Third, aflibercept also binds to VEGF-B and placental growth factor (PlGF), unlike ranibizumab or bevacizumab. PlGF-VEGFR1 pathway contributes to inflammation by triggering production of proinflammatory cytokines.
Thus, I would like to investigate the efficacy of aflibercept for reducing inflammation in DME. Therapeutic effects of aflibercept on reduction of DME in the context of amelioration of inflammation will be proved using sCD14 and HF as surrogate markers in this proposed study. Besides sCD14, tracking the cytokines including MCP-1, IL-6, and ICAM-1 in the AH in a well-controlled prospective setting of aflibercept treatments will enhance our understanding regarding the role of inflammation on DME, and the importance of aflibercept for decreasing ocular inflammation in DME patients.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aflibercept injection group | Experimental | Drug: Aflibercept Injectiondrug: Eylea (aflibercept) (11.12mg/0.278ml) dose: 2mg (0.05ml) usage: With topical anesthesia and intravitreal injection of aflibercpt in aseptic condition. frequency and duration: monthly intravitreal aflibercept injections. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adults ≥ 19 years with type 1 or 2 diabetes mellitus.
- Patients with DME secondary to diabetes mellitus involving the center of the macula (defined as the OCT center subfield) in the study eye.
- Decrease in vision determined to be primarily the result of DME in the study eye.
- BCVA ETDRS letter score of 80 to 24 (20/25 to 20/320) in the study eye.
- Retinal thickness ≥ 300 µm as assessed by OCT in the study eye.
Key exclusion criteria (22 listed)
- Ocular conditions with a poorer prognosis in the fellow eye than in the study eye.
- History of vitreoretinal surgery in the study eye.
- Previous treatment with intraocular anti-angiogenic drugs (bevacizumab, ranibizumab etc.) or laser photocoagulation in the study eye within 90 days.
- Previous use of intraocular or periocular corticosteroids in the study eye within 120 days of day 1.
- Invasive intraocular surgery incluing cataract surgery within 90 days of day 1.
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 |
|---|---|---|
| Aflibercept InjectionAlso: EyleaTotal 5 times of monthly intravitreal aflibercept injections will be done. | Drug | Aflibercept injection group |
Primary outcome
Change in the level of sCD14 in the aqueous humor
Time frame: From baseline to week 20
Change in the level of sCD14 in the aqueous humor measured by ELISA
4 secondary outcomes
Change in the levels of cytokines (MCP-1, IL-6, ICAM-1) in the aqueous humor
Time frame: From baseline to week 20
Change in the number of hyperreflective foci (HF) on optical coherence tomography (OCT)
Time frame: From baseline to week 20
Change in the thickeness of macula on OCT
Time frame: From baseline to week 20
Change in mean visual acuity (ETDRS)
Time frame: From baseline to week 20
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 29 May 2024.
- Background: PubMed 29392317Lee H, Jang H, Choi YA, Kim HC, Chung H. Association Between Soluble CD14 in the Aqueous Humor and Hyperreflective Foci on Optical Coherence Tomography in Patients With Diabetic Macular Edema. Invest Ophthalmol Vis Sci. 2018 Feb 1;59(2):715-721. doi: 10.1167/iovs.17-23042.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Aflibercept Injection in people with Diabetic Macular Edema, run by Hyewon Chung at 1 site in South Korea.
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 6 inclusion and 22 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 29 May 2024. 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 South Korea. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Change in the level of sCD14 in the aqueous humor (time frame: From baseline to week 20). 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 NCT03780361, which also lists 1 linked publication.
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 29 May 2024.