Patients With Primary Nasal PterygiumPhase 1NCT04878835
Effects of Ranibizumab in Primary Pterygium Surgery
A Phase 1 study testing intralesional ranibizumab in people with Patients With Primary Nasal Pterygium, run by Universiti Sains Malaysia at 1 site in Malaysia.
Trial summary
Pterygium is a common ocular surface disease in Malaysia. Without treatment, it can lead to severe visual impairment. Recurrence is the commonest complication and novel treatment approaches are crucial to prevent vision loss. Read more about this study
- Who is it for?
- Ages 40 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Patients With Primary Nasal Pterygium
- What is being tested?
- intralesional ranibizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteMalaysia
- Study dates
- 1 May 2018to 30 Apr 2020
- Phase
- Phase 1
- 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 40 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- primary nasal grade 2 to 3 pterygium based on the clinical stages outlined by Johnston et al (2004)
- who consented for pterygium excision and conjunctival autograft surgery
Who cannot join
- cornea pathology such as scarring, history of herpetic keratitis, eyelid abnormalities, previous ocular surgery, ocular trauma, and ocular or systemic inflammatory disease
- Pregnant women and lactating mothers
Trial locations and contacts
1 site in 1 country.
Malaysia1 site
Hospital Universiti Sains Malaysia
Kota Bharu, Kelantan, 16150
About this study
Official title: Effects of Ranibizumab on Microvasculature, Oxidative Stress and Recurrence in Primary Pterygium Surgery
Pterygium is a common ocular surface disease in Malaysia. Without treatment, it can lead to severe visual impairment. Recurrence is the commonest complication and novel treatment approaches are crucial to prevent vision loss. The biological processes underlying the formation of pterygium are complex, but central to its pathogenesis is the angiogenic cytokine vascular endothelial growth factor (VEGF). VEGF is upregulated under conditions of increased oxidative stress, which plays an integral role in pterygium development (Cardenas-Cantu et al., 2016, Karaman, 2018, Norrby, 1998, Rossino et al., 2020, Shibunya, 2011).Various biomarkers on pterygium have been identified and are useful to determine the effectiveness of new modality treatment for pterygium. These markers can be identified via histopathological stain such as Masson Trichrome to observe changes of collagen fibres. Other identifiable markers include the use of special immunohistochemical stain such as anti CD34 antibody for microvascular density and anti-8-OHdG antibody for oxidative changes in the pterygium tissue. By analyzing the changes with or without Ranibizumab injection in addition to observation of clinical recurrence rate of pterygium, we are able to conclude the effectiveness of anti-VEGF on pterygium recurrence. The aim of the study was to evaluate the association between collagen fibres changes, microvascular density changes and inflammation resultant from oxidative stress with the clinical recurrence of pterygium following intralesional Ranibizumab injection in comparison to control group.
Read the detailed description
This is a prospective interventional study conducted from May 2018 to April 2020. Patients with primary pterygium who attended eye clinic Hospital Universiti Sains Malaysia (HUSM) Kubang Kerian, Kelantan and fulfilled the inclusion and exclusion criteria were recruited as participants of this study. Convenient sampling method was applied for participants' recruitment where all patients will be given thorough explanation in regards to the study and subsequently divided into interventional and control group. Intervention group participants were given intralesional Ranibizumab (0.5mg/ 0.05mL) 2 weeks prior to pterygium excision surgery. Both groups of participants undergo pterygium excision with autologous conjunctival graft surgery thereafter. Excised pterygium tissues were sent to the laboratory for slide preparation and staining with specific reagents including Masson Trichrome for collagen fibers, anti CD34 antibody for microvascular density and anti-8 OHdG antibody for oxidative stress changes. Slides were then analysed by the pathologist and statistical analysis of the results were carried out with the Statistical Package for the Social Sciences (SPSS) Version 26.0. All participants had intralesional Ranibizumab injection and pterygium excision with autologous conjunctival graft surgery in May 2018. They were scheduled for follow-up visits for the next 24 months to observe for complications of intralesional Ranibizumab injection, pterygium excision and conjunctival autograft surgery and any signs of recurrence.
- Conditions
- Patients With Primary Nasal Pterygium
- Being tested
- intralesional ranibizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intralesional ranibizumabBiological
Lucentis; Genentech, Inc, San Francisco, California, USA 0.5mg/ 0.05mL
| Study group | Role | What they receive |
|---|---|---|
| Control group | No intervention | No intervention was given. No intralesional ranibizumab (Lucentis; Genentech, Inc, San Francisco, California, USA 0.5mg/ 0.05mL) was given at 2 weeks prior to pterygium excision surgery |
| Intervention group | Experimental | The interventional group was given intralesional ranibizumab (Lucentis; Genentech, Inc, San Francisco, California, USA 0.5mg/ 0.05mL) 2 weeks prior to pterygium excision surgery Receives: Biological: intralesional ranibizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Microvascular Density (MVD) using anti-CD34 antibody staining, classified based on the Weidner scoring system.
MVD is a reflection of angiogenesis (Norrby, 1998). The effects of anti-VEGF on MVD of the excised tissue were assessed using anti-CD34 antibody (50 µg at 1 mg/ml at dilution of 1:50-1:100, QBEnd/10, Mouse anti-Human, Dako, North America).
Measured: After pterygium excision surgery, tissues were sent to the histopathological laboratory where microvascular density was assessed within two weeks
Secondary outcomes (1)
Oxidative Stress using eight-hydroxyguanosine (8-OHdG) staining, based on the percentage of positively stained cells viewed under 400x high-power field magnification.
8-OHdG is an oxidative stress biomarker which has been observed to have a significant association with primary pterygium Ismaeel et al. (2010).
Measured: After pterygium excision surgery, tissues were sent to the histopathological laboratory where assessment for oxidative stress via 8-OHdG staining was performed within two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2021
- Study start1 May 2018
- Primary completion1 Apr 2020
- Study completion30 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Patients With Primary Nasal PterygiumStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universiti Sains Malaysia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kueh Yee Cheng, PhD, Universiti Sains Malaysia
- Investigators
- Jin Yi Yap, MMed, Principal investigator, Universiti Sains Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04878835
- Sponsor's protocol ID
- USM/JEPeM/18010009
- Status last verified
- May 2021
- First submitted
- 26 Apr 2021
- Last updated
- 10 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ismaeel OM, Jaafar H, Ibrahim M. Detection of 8-hydroxydeoxyguanosine enzyme in recurrent pterygium raising a question on its role on recurrence. Int J Ophthalmol. 2010;3(3):245-8. doi: 10.3980/j.issn.2222-3959.2010.03.15. Epub 2010 Sep 18.
PubMed 22553564Johnston SC, Williams PB, Sheppard JDJr. A Comprehensive System for Pterygium Classification. Invest Ophthalmol Vis Sci. 2004; 45(13): 2940.
Norrby K. Microvascular density in terms of number and length of microvessel segments per unit tissue volume in mammalian angiogenesis. Microvasc Res. 1998 Jan;55(1):43-53. doi: 10.1006/mvre.1997.2054.
PubMed 9473408Shibuya M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes Cancer. 2011 Dec;2(12):1097-105. doi: 10.1177/1947601911423031.
PubMed 22866201Karaman S, Leppanen VM, Alitalo K. Vascular endothelial growth factor signaling in development and disease. Development. 2018 Jul 20;145(14):dev151019. doi: 10.1242/dev.151019.
PubMed 30030240Cardenas-Cantu E, Zavala J, Valenzuela J, Valdez-Garcia JE. Molecular Basis of Pterygium Development. Semin Ophthalmol. 2016;31(6):567-83. doi: 10.3109/08820538.2014.971822. Epub 2014 Nov 21.
PubMed 25415268Rossino MG, Lulli M, Amato R, Cammalleri M, Monte MD, Casini G. Oxidative Stress Induces a VEGF Autocrine Loop in the Retina: Relevance for Diabetic Retinopathy. Cells. 2020 Jun 11;9(6):1452. doi: 10.3390/cells9061452.
PubMed 32545222
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Ranibizumab on Microvasculature, Oxidative Stress and Recurrence in Primary Pterygium Surgery
- ClinicalTrials.gov ID
- NCT04878835
- Acronym / sponsor ID
- USM/JEPeM/18010009
- Conditions
- Patients With Primary Nasal Pterygium
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Universiti Sains MalaysiaUniversity, hospital or other
- Study start
- 1 May 2018 (actual)
- Primary completion
- 1 Apr 2020 (actual)
- Study completion
- 30 Apr 2020 (actual)
- First posted
- 10 May 2021 (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.
Pterygium is a common ocular surface disease in Malaysia. Without treatment, it can lead to severe visual impairment. Recurrence is the commonest complication and novel treatment approaches are crucial to prevent vision loss. The biological processes underlying the formation of pterygium are complex, but central to its pathogenesis is the angiogenic cytokine vascular endothelial growth factor (VEGF). VEGF is upregulated under conditions of increased oxidative stress, which plays an integral role in pterygium development (Cardenas-Cantu et al., 2016, Karaman, 2018, Norrby, 1998, Rossino et al., 2020, Shibunya, 2011).Various biomarkers on pterygium have been identified and are useful to determine the effectiveness of new modality treatment for pterygium. These markers can be identified via histopathological stain such as Masson Trichrome to observe changes of collagen fibres. Other identifiable markers include the use of special immunohistochemical stain such as anti CD34 antibody for microvascular density and anti-8-OHdG antibody for oxidative changes in the pterygium tissue. By analyzing the changes with or without Ranibizumab injection in addition to observation of clinical recurrence rate of pterygium, we are able to conclude the effectiveness of anti-VEGF on pterygium recurrence. The aim of the study was to evaluate the association between collagen fibres changes, microvascular density changes and inflammation resultant from oxidative stress with the clinical recurrence of pterygium following intralesional Ranibizumab injection in comparison to control group.
Detailed description
This is a prospective interventional study conducted from May 2018 to April 2020. Patients with primary pterygium who attended eye clinic Hospital Universiti Sains Malaysia (HUSM) Kubang Kerian, Kelantan and fulfilled the inclusion and exclusion criteria were recruited as participants of this study. Convenient sampling method was applied for participants' recruitment where all patients will be given thorough explanation in regards to the study and subsequently divided into interventional and control group. Intervention group participants were given intralesional Ranibizumab (0.5mg/ 0.05mL) 2 weeks prior to pterygium excision surgery. Both groups of participants undergo pterygium excision with autologous conjunctival graft surgery thereafter. Excised pterygium tissues were sent to the laboratory for slide preparation and staining with specific reagents including Masson Trichrome for collagen fibers, anti CD34 antibody for microvascular density and anti-8 OHdG antibody for oxidative stress changes. Slides were then analysed by the pathologist and statistical analysis of the results were carried out with the Statistical Package for the Social Sciences (SPSS) Version 26.0. All participants had intralesional Ranibizumab injection and pterygium excision with autologous conjunctival graft surgery in May 2018. They were scheduled for follow-up visits for the next 24 months to observe for complications of intralesional Ranibizumab injection, pterygium excision and conjunctival autograft surgery and any signs of recurrence.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | No intervention | –No intervention was given. No intralesional ranibizumab (Lucentis; Genentech, Inc, San Francisco, California, USA 0.5mg/ 0.05mL) was given at 2 weeks prior to pterygium excision surgery |
| Intervention group | Experimental | Biological: intralesional ranibizumabThe interventional group was given intralesional ranibizumab (Lucentis; Genentech, Inc, San Francisco, California, USA 0.5mg/ 0.05mL) 2 weeks prior to pterygium excision surgery |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- primary nasal grade 2 to 3 pterygium based on the clinical stages outlined by Johnston et al (2004)
- who consented for pterygium excision and conjunctival autograft surgery
Key exclusion criteria (2 listed)
- cornea pathology such as scarring, history of herpetic keratitis, eyelid abnormalities, previous ocular surgery, ocular trauma, and ocular or systemic inflammatory disease
- Pregnant women and lactating mothers
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 |
|---|---|---|
| intralesional ranibizumabLucentis; Genentech, Inc, San Francisco, California, USA 0.5mg/ 0.05mL | Biological | Intervention group |
Primary outcome
Microvascular Density (MVD) using anti-CD34 antibody staining, classified based on the Weidner scoring system.
Time frame: After pterygium excision surgery, tissues were sent to the histopathological laboratory where microvascular density was assessed within two weeks
MVD is a reflection of angiogenesis (Norrby, 1998). The effects of anti-VEGF on MVD of the excised tissue were assessed using anti-CD34 antibody (50 µg at 1 mg/ml at dilution of 1:50-1:100, QBEnd/10, Mouse anti-Human, Dako, North America).
1 secondary outcome
Oxidative Stress using eight-hydroxyguanosine (8-OHdG) staining, based on the percentage of positively stained cells viewed under 400x high-power field magnification.
Time frame: After pterygium excision surgery, tissues were sent to the histopathological laboratory where assessment for oxidative stress via 8-OHdG staining was performed within two weeks
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 10 May 2021.
- Background: PubMed 22553564Ismaeel OM, Jaafar H, Ibrahim M. Detection of 8-hydroxydeoxyguanosine enzyme in recurrent pterygium raising a question on its role on recurrence. Int J Ophthalmol. 2010;3(3):245-8. doi: 10.3980/j.issn.2222-3959.2010.03.15. Epub 2010 Sep 18.
- BackgroundJohnston SC, Williams PB, Sheppard JDJr. A Comprehensive System for Pterygium Classification. Invest Ophthalmol Vis Sci. 2004; 45(13): 2940.
- Background: PubMed 9473408Norrby K. Microvascular density in terms of number and length of microvessel segments per unit tissue volume in mammalian angiogenesis. Microvasc Res. 1998 Jan;55(1):43-53. doi: 10.1006/mvre.1997.2054.
- Background: PubMed 22866201Shibuya M. Vascular Endothelial Growth Factor (VEGF) and Its Receptor (VEGFR) Signaling in Angiogenesis: A Crucial Target for Anti- and Pro-Angiogenic Therapies. Genes Cancer. 2011 Dec;2(12):1097-105. doi: 10.1177/1947601911423031.
- Background: PubMed 30030240Karaman S, Leppanen VM, Alitalo K. Vascular endothelial growth factor signaling in development and disease. Development. 2018 Jul 20;145(14):dev151019. doi: 10.1242/dev.151019.
- Background: PubMed 25415268Cardenas-Cantu E, Zavala J, Valenzuela J, Valdez-Garcia JE. Molecular Basis of Pterygium Development. Semin Ophthalmol. 2016;31(6):567-83. doi: 10.3109/08820538.2014.971822. Epub 2014 Nov 21.
- Background: PubMed 32545222Rossino MG, Lulli M, Amato R, Cammalleri M, Monte MD, Casini G. Oxidative Stress Induces a VEGF Autocrine Loop in the Retina: Relevance for Diabetic Retinopathy. Cells. 2020 Jun 11;9(6):1452. doi: 10.3390/cells9061452.
- Individual participant dataSharing planned: No
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.
Jin Yi Yap, MMed principal investigator
Universiti Sains Malaysia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing intralesional ranibizumab in people with Patients With Primary Nasal Pterygium, run by Universiti Sains Malaysia at 1 site in Malaysia.
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 2 inclusion and 2 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 10 May 2021. 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 Malaysia. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Microvascular Density (MVD) using anti-CD34 antibody staining, classified based on the Weidner scoring system. (time frame: After pterygium excision surgery, tissues were sent to the histopathological laboratory where microvascular density was assessed within two weeks). 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 NCT04878835, which also lists 7 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 10 May 2021.