Corticosteroid Induced Ocular Hypertension/GlaucomaNCT03250819
Gene Polymorphisms of Corticosteroid-induced Ocular Hypertension
An observational study of Corticosteroid Induced Ocular Hypertension/Glaucoma, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Glaucoma is one of the most prevalent eye diseases and the second most common cause of blindness worldwide. The most common form is primary open angle glaucoma (POAG). Glaucoma is a slowly progressing neuropathy of the optic nerve that causes loss of visual field and eventually blindness. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corticosteroid Induced Ocular Hypertension/Glaucoma
- What is being tested?
- SNP analysis
- How many people
- 370 participants
- Where
- 1 siteNetherlands
- Study dates
- 13 Sep 2017to 1 May 2020
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients who started topical, intravitreal or subconjunctival corticosteroids will be included at the University Eye Clinic Maastricht of the Maastricht University Medical Centre+, the Netherlands. The participants will be divided in two groups: cases who are corticosteroid responder (n=150) and controls exposed to corticosteroids who did not respond with an IOP increase (n=300).
Who may be able to join
- Use of corticosteroids:
- Patients treated with Ozurdex (an intravitreal dexamethasone implant
- Patients treated with subconjunctival Triamcinolone/ Celestone injections
- Patients treated with corticosteroids after a corneal surgery
- Patients treated with corticosteroids after a refractive surgery
- Patients treated with corticosteroids after a cataract surgery
Show all 11Show fewer
- Patients treated with corticosteroids for macular edema
- Patients exposed to corticosteroids for other diseases such as uveitis
- When using topical corticosteroids, time of use > 3 months
- Age > 18 year and mentally competent
- Patient from the Maastricht University Medical Centre+ (MUMC+), the Netherlands
Who cannot join
- Age < 18 year
- Mentally not able to participate or give permission
- Not able to communicate in Dutch
- Patients with a type of uveitis that might cause a decrease of the IOP
- When using topical corticosteroids, time of use < 3 months.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
University Eye Clinic Maastricht, Maastricht UMC+
Maastricht, Limburg, 6229 HX
About this study
Official title: Genetic Association Study on Corticosteroid-induced Elevation of the Intraocular Pressure
Glaucoma is one of the most prevalent eye diseases and the second most common cause of blindness worldwide. The most common form is primary open angle glaucoma (POAG). Glaucoma is a slowly progressing neuropathy of the optic nerve that causes loss of visual field and eventually blindness. Elevated intra-ocular pressure (IOP) is the most important risk factor.
Corticosteroids, which are often used for the treatment of many diseases in ophthalmology and other specialities, may cause an elevation of the IOP. It is estimated that corticosteroids induce ocular hypertension in approximately 18%-36% of the general population and in patients with POAG this percentage can be as high as 92%. When the treatment is sustained, this can cause a glaucomatous neuropathy of the optic nerve (corticosteroid-induced glaucoma).
Read more
The precise pathogenic mechanism isn't clear yet. Genetic factors are likely to affect the susceptibility to corticosteroid response. Therefore, an overview of the genetic mechanisms of corticosteroid-induced glaucoma can give more insight in the pathogenesis. In this study the researchers investigate the occurrence of SNPs (single nucleotide polymorphisms) in 150 cases with a steroid-response in comparison with 300 controls exposed to corticosteroids without a steroid-response.
Up to now, one small GWAS has been conducted comparing 32 patients with and without corticosteroid-induced ocular hypertension after treatment with intravitreal triamcinolone. In this study, two SNPs proximal of the transcriptional start site (near the 5') of HCG22 on chromosome 6 were identified. However, this is a rather small sample population and the investigators didn't match for the underlying disease. Further, in another small study, Hogewind et al. performed SNP analysis in multiple genes (SFRS3, FKBP4, FKBP5, and NR3C1) in corticosteroid-induced ocular hypertension.
This study enables the investigators to identify patients at risk for developing corticosteroid-induced glaucoma and to gain a better insight in the pathogenesis. This may also lead to the discovery of biomarkers that indicate an increased risk of developing a steroid-induced glaucoma and new prevention and treatment strategies, which are necessary as the treatment of corticosteroid induced-glaucoma now only focuses at lowering the IOP and can still be challenging.
- Being tested
- SNP analysis
- Medical subject headings
- Glaucoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SNP analysisOther
The collected blood samples will be used to investigate the occurrence of SNPs (single nucleotide polymorphisms) in both study groups
| Study group | Role | What they receive |
|---|---|---|
| Corticosteroid responders | Patients who develop an increase in eye pressure after the use of corticosteroids Receives: Other: SNP analysis | |
| Non-corticosteroid responders | Patients who use/used corticosteroids but didn't develop an increase in eye pressure Receives: Other: SNP analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in SNP's in corticosteroid responders and non-responders
What are the differences in SNPs in patients with corticosteroid-induced ocular hypertension in comparison with patients exposed to corticosteroids who do not respond with an IOP increase
Measured: At the time of inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2017
- Study start13 Sep 2017
- Primary completion6 Feb 2019
- Study completion1 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Corticosteroid Induced Ocular Hypertension/GlaucomaStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- 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
- Other
- Enrolment
- 370 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Johannes SA Schouten, MD, PhD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03250819
- Sponsor's protocol ID
- NL58992.068.17
- Status last verified
- May 2020
- First submitted
- 11 Aug 2017
- Last updated
- 1 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Jeong S, Patel N, Edlund CK, Hartiala J, Hazelett DJ, Itakura T, Wu PC, Avery RL, Davis JL, Flynn HW, Lalwani G, Puliafito CA, Wafapoor H, Hijikata M, Keicho N, Gao X, Argueso P, Allayee H, Coetzee GA, Pletcher MT, Conti DV, Schwartz SG, Eaton AM, Fini ME. Identification of a Novel Mucin Gene HCG22 Associated With Steroid-Induced Ocular Hypertension. Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2737-48. doi: 10.1167/iovs.14-14803.
PubMed 25813999Fini ME, Schwartz SG, Gao X, Jeong S, Patel N, Itakura T, Price MO, Price FW Jr, Varma R, Stamer WD. Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine. Prog Retin Eye Res. 2017 Jan;56:58-83. doi: 10.1016/j.preteyeres.2016.09.003. Epub 2016 Sep 22.
PubMed 27666015
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Association Study on Corticosteroid-induced Elevation of the Intraocular Pressure
- ClinicalTrials.gov ID
- NCT03250819
- Acronym / sponsor ID
- NL58992.068.17
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 370 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- 13 Sep 2017 (actual)
- Primary completion
- 6 Feb 2019 (actual)
- Study completion
- 1 May 2020 (actual)
- First posted
- 16 Aug 2017 (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.
Glaucoma is one of the most prevalent eye diseases and the second most common cause of blindness worldwide. The most common form is primary open angle glaucoma (POAG). Glaucoma is a slowly progressing neuropathy of the optic nerve that causes loss of visual field and eventually blindness. Elevated intra-ocular pressure (IOP) is the most important risk factor.
Corticosteroids, which are often used for the treatment of many diseases in ophthalmology and other specialities, may cause an elevation of the IOP. It is estimated that corticosteroids induce ocular hypertension in approximately 18%-36% of the general population and in patients with POAG this percentage can be as high as 92%. When the treatment is sustained, this can cause a glaucomatous neuropathy of the optic nerve (corticosteroid-induced glaucoma).
The precise pathogenic mechanism isn't clear yet. Genetic factors are likely to affect the susceptibility to corticosteroid response. Therefore, an overview of the genetic mechanisms of corticosteroid-induced glaucoma can give more insight in the pathogenesis. In this study the researchers investigate the occurrence of SNPs (single nucleotide polymorphisms) in 150 cases with a steroid-response in comparison with 300 controls exposed to corticosteroids without a steroid-response.
Up to now, one small GWAS has been conducted comparing 32 patients with and without corticosteroid-induced ocular hypertension after treatment with intravitreal triamcinolone. In this study, two SNPs proximal of the transcriptional start site (near the 5') of HCG22 on chromosome 6 were identified. However, this is a rather small sample population and the investigators didn't match for the underlying disease. Further, in another small study, Hogewind et al. performed SNP analysis in multiple genes (SFRS3, FKBP4, FKBP5, and NR3C1) in corticosteroid-induced ocular hypertension.
This study enables the investigators to identify patients at risk for developing corticosteroid-induced glaucoma and to gain a better insight in the pathogenesis. This may also lead to the discovery of biomarkers that indicate an increased risk of developing a steroid-induced glaucoma and new prevention and treatment strategies, which are necessary as the treatment of corticosteroid induced-glaucoma now only focuses at lowering the IOP and can still be challenging.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Corticosteroid responders | – | Other: SNP analysisPatients who develop an increase in eye pressure after the use of corticosteroids |
| Non-corticosteroid responders | – | Other: SNP analysisPatients who use/used corticosteroids but didn't develop an increase in eye pressure |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who started topical, intravitreal or subconjunctival corticosteroids will be included at the University Eye Clinic Maastricht of the Maastricht University Medical Centre+, the Netherlands. The participants will be divided in two groups: cases who are corticosteroid responder (n=150) and controls exposed to corticosteroids who did not respond with an IOP increase (n=300).
Key inclusion criteria (11 listed)
- Use of corticosteroids:
- Patients treated with Ozurdex (an intravitreal dexamethasone implant
- Patients treated with subconjunctival Triamcinolone/ Celestone injections
- Patients treated with corticosteroids after a corneal surgery
- Patients treated with corticosteroids after a refractive surgery
Key exclusion criteria (5 listed)
- Age < 18 year
- Mentally not able to participate or give permission
- Not able to communicate in Dutch
- Patients with a type of uveitis that might cause a decrease of the IOP
- When using topical corticosteroids, time of use < 3 months.
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 |
|---|---|---|
| SNP analysisThe collected blood samples will be used to investigate the occurrence of SNPs (single nucleotide polymorphisms) in both study groups | Other | Corticosteroid responders, Non-corticosteroid responders |
Primary outcome
Differences in SNP's in corticosteroid responders and non-responders
Time frame: At the time of inclusion
What are the differences in SNPs in patients with corticosteroid-induced ocular hypertension in comparison with patients exposed to corticosteroids who do not respond with an IOP increase
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 1 Jun 2020.
- Background: PubMed 25813999Jeong S, Patel N, Edlund CK, Hartiala J, Hazelett DJ, Itakura T, Wu PC, Avery RL, Davis JL, Flynn HW, Lalwani G, Puliafito CA, Wafapoor H, Hijikata M, Keicho N, Gao X, Argueso P, Allayee H, Coetzee GA, Pletcher MT, Conti DV, Schwartz SG, Eaton AM, Fini ME. Identification of a Novel Mucin Gene HCG22 Associated With Steroid-Induced Ocular Hypertension. Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2737-48. doi: 10.1167/iovs.14-14803.
- Background: PubMed 27666015Fini ME, Schwartz SG, Gao X, Jeong S, Patel N, Itakura T, Price MO, Price FW Jr, Varma R, Stamer WD. Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine. Prog Retin Eye Res. 2017 Jan;56:58-83. doi: 10.1016/j.preteyeres.2016.09.003. Epub 2016 Sep 22.
- Individual participant dataSharing planned: Undecided
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.
Johannes SA Schouten, MD, PhD principal investigator
Maastricht University Medical Center
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 Corticosteroid Induced Ocular Hypertension/Glaucoma, run by Maastricht University Medical Center at 1 site in Netherlands.
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 11 inclusion and 5 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 1 Jun 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 Netherlands. 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?
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?
Differences in SNP's in corticosteroid responders and non-responders (time frame: At the time of inclusion). 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 NCT03250819, which also lists 2 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 1 Jun 2020.