Intraocular PressureEarly Phase 1BrimonidineNCT01144494
Aqueous Humor Dynamics and Brimonidine
A Early Phase 1 study testing Brimonidine and Artificial tears in people with Intraocular Pressure, run by University of Nebraska at 1 site in United States.
Trial summary
This single-center, investigator-masked, crossover study is designed to investigate the circadian rhythms of aqueous humor dynamics in human subjects with ocular hypertension (OHT) before and after intervention with a commonly used ocular hypotensive medication, brimonidine for six weeks. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Intraocular Pressure
- What is being tested?
- Brimonidine and Artificial tears
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2010to 1 Oct 2011
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Subjects must be 19 years of age or older
- Subjects must exhibit a history of untreated IOPs between 21 and 35 mmHg (inclusive)
Who cannot join
- Age less than nineteen years old
- Women who are pregnant, lactating or of childbearing potential who are not using birth control measures.
- Aphakia or pseudophakia
- Best corrected visual acuity worse than 20/60 in either eye
- Chronic or recurrent severe ocular inflammatory disease
- Ocular infection or inflammation within (3) months of screening visit.
Show all 23Show fewer
- History of clinically significant or progressive retinal disease such as retinal degeneration, diabetic retinopathy or retinal detachment.
- Any abnormality preventing reliable tonometry of either eye.
- Previous exposure to: beta-adrenergic antagonists, topical prostaglandin analogues within six (6) weeks of the baseline visit; α-adrenergic agonists within two (2) weeks of the baseline visit; and cholinergic agonists and carbonic anhydrase inhibitors within five (5) days of the treatment initiation visit.
- History of any severe ocular pathology (including severe dry eye) that would prelude the administration of a topical beta blocker, carbonic anhydrase inhibitor, or a topical prostaglandin.
- Any eye with a cup-to-disc ratio greater than 0.8.
- History of intraocular surgery
- History of ocular laser surgery
- History of severe or serious hypersensitivity to brimonidine or its vehicle.
- History of severe, unstable, or uncontrolled cardiovascular, hepatic or renal disease.
- History of bronchial asthma or chronic obstructive pulmonary disease (COPD).
- Less than one month (prior to baseline) stable dosing regimen of any non-glaucoma medication that would affect IOP.
- Gonioscopy angle < 2.
- Inability to be dosed with treatment medication
- Inability to discontinue contact lens wear.
- Therapy with any investigational agent within 30 days of screening.
- Use of any additional topical or systemic adjunctive ocular hypotensive medications during the study.
- History of open angle glaucoma (either primary open angle glaucoma or other cause of open angle glaucoma) or narrow angle glaucoma.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68198-5540
About this study
Official title: Circadian Rhythms of Aqueous Humor Dynamics in Subjects With Ocular Hypertension Using Brimonidine
This single-center, investigator-masked, crossover study is designed to investigate the circadian rhythms of aqueous humor dynamics in human subjects with ocular hypertension (OHT) before and after intervention with a commonly used ocular hypotensive medication, brimonidine for six weeks.
Read the detailed description
Currently, the only effective treatment to prevent disease progression is lowering of the intraocular pressure (IOP).2 Usually, clinical IOP measurements are performed during the day with little information collected on nocturnal IOP. A recent surge of interest in nocturnal IOPs stems from the hypothesis that significant glaucomatous damage may occur at night.4,5 In response, some investigators have advocated particular classes of glaucoma medications based on their nocturnal IOP effects.6-8 The most efficacious drug on the market may not be the preferred treatment if it is ineffective at night. Therefore, the understanding of nighttime IOP and the aqueous humor dynamics that control it has important scientific, clinical, and commercial implications.
Previous research on glaucoma medications has been limited to the effects of ocular hypotensive drugs on 24-hour IOP or daytime aqueous humor dynamics. Few studies have evaluated nocturnal aqueous humor dynamics. The investigators recently completed studies of day and night differences in aqueous humor dynamics in patients treated with drugs from three different classes that include a prostaglandin analog, a beta blocker and a carbonic anhydrase inhibitor. The current study is designed to elucidate the physiological mechanisms driving the efficacy of brimonidine, an alpha 2 adrenergic agonist, throughout the 24-hour period, i.e. circadian rhythms in aqueous humor dynamics. Based on what the investigators know of 24 hour IOPs this drug is expected to work well at night potentially by enhancing uveoscleral outflow. This study will test this hypothesis.
This single-center, investigator-masked, crossover study is designed to investigate the circadian rhythms of aqueous humor dynamics in human subjects with ocular hypertension (OHT) before and after intervention with a commonly used ocular hypotensive medication, brimonidine. Thirty participants with ocular hypertension (intraocular pressure greater than 20mmHg) will be enrolled.
The subjects will undergo a baseline phase and medication phase using brimonidine. At both phases, they will attend a daytime and a nighttime study visit in which fluorophotometry will be used to calculate aqueous flow (production), trabecular outflow facility, and uveoscleral outflow. At the completion of the study, subjects will return to their previous ophthalmic clinic.
- Conditions
- Intraocular Pressure
- Being tested
- Brimonidine, Artificial tears
- Keywords
- Aqueous Humor Dynamics, Aqueous Humor Dynamics and Circadian Rhythms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrimonidineDrug
Also called Mirvaso, Alphagan P
One drop of brimonidine in each eye three times a day for six weeks.
Artificial tearsDrug
Also called Systane
Lubricating drops added three times a day for six weeks
| Study group | Role | What they receive |
|---|---|---|
| Intraocular pressure lowering drug | Active comparator | Eyedrops for lowering intraocular pressure Receives: Drug: Brimonidine |
| Artificial Tears | Placebo comparator | Lubricated eye drops Receives: Drug: Artificial tears |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seated Day-time IOP 9 am and 11 am, Supine Day-time IOP 9 am and 11 am, and Seated Night-time IOP 9 pm and 11 pm
Seated day-time and supine day-time IOP was measured by pneumatonometer at 9 am and 11 am. Seated night-time IOP was measured at 9 pm and 11 pm.
Measured: 6 weeks
Supine Night-time & Day-time Seated Episcleral Venous Pressure (EVP)
The episcleral venous pressure was measured using the episcleral venomanometer
Measured: 6 weeks plus 2 days
Secondary outcomes (3)
Aqueous Flow
Measured by fluorophotometry during the day and night on 29 participants.
Measured: 6 weeks
Uveoscleral Outflow
Calculated from the modified Goldmann equation using data obtained at 9 am and 11 am. Goldmann equation involves data from aqueous flow, tonography/outflow facility, episcleral venous pressure and IOP. Tonography/outflow facility data on 2 participants were not reliable, therefore uveosleral outflow analysis was performed on 27 participants.
Measured: 6 weeks
Outflow Facility
Calculated from the measurement taken during the day and night. Tonography/outflow facility data was not reliable in 2 of the participants, therefore analysis was conducted on data from 27 participants.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2010 (estimated)
- Study start1 Aug 2010
- Primary completion1 Oct 2011
- Study completion1 Oct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Intraocular PressureStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Carol B Toris, PhD, Principal investigator, Research Instructor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01144494
- Sponsor's protocol ID
- 0220-10-FB
- Acronym
- Brimonidine
- Status last verified
- Nov 2023
- First submitted
- 11 Jun 2010
- Last updated
- 28 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Fan S, Agrawal A, Gulati V, Neely DG, Toris CB. Daytime and nighttime effects of brimonidine on IOP and aqueous humor dynamics in participants with ocular hypertension. J Glaucoma. 2014 Jun-Jul;23(5):276-81. doi: 10.1097/IJG.0000000000000051.
PubMed 24886701
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Circadian Rhythms of Aqueous Humor Dynamics in Subjects With Ocular Hypertension Using Brimonidine
- ClinicalTrials.gov ID
- NCT01144494
- Acronym / sponsor ID
- Brimonidine / 0220-10-FB
- Conditions
- Intraocular Pressure
- Keywords
- Aqueous Humor Dynamics, Aqueous Humor Dynamics and Circadian Rhythms
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 1 Aug 2010 (actual)
- Primary completion
- 1 Oct 2011 (actual)
- Study completion
- 1 Oct 2011 (actual)
- First posted
- 15 Jun 2010 (estimated)
- Results
- Posted 24 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This single-center, investigator-masked, crossover study is designed to investigate the circadian rhythms of aqueous humor dynamics in human subjects with ocular hypertension (OHT) before and after intervention with a commonly used ocular hypotensive medication, brimonidine for six weeks.
Detailed description
Currently, the only effective treatment to prevent disease progression is lowering of the intraocular pressure (IOP).2 Usually, clinical IOP measurements are performed during the day with little information collected on nocturnal IOP. A recent surge of interest in nocturnal IOPs stems from the hypothesis that significant glaucomatous damage may occur at night.4,5 In response, some investigators have advocated particular classes of glaucoma medications based on their nocturnal IOP effects.6-8 The most efficacious drug on the market may not be the preferred treatment if it is ineffective at night. Therefore, the understanding of nighttime IOP and the aqueous humor dynamics that control it has important scientific, clinical, and commercial implications.
Previous research on glaucoma medications has been limited to the effects of ocular hypotensive drugs on 24-hour IOP or daytime aqueous humor dynamics. Few studies have evaluated nocturnal aqueous humor dynamics. The investigators recently completed studies of day and night differences in aqueous humor dynamics in patients treated with drugs from three different classes that include a prostaglandin analog, a beta blocker and a carbonic anhydrase inhibitor. The current study is designed to elucidate the physiological mechanisms driving the efficacy of brimonidine, an alpha 2 adrenergic agonist, throughout the 24-hour period, i.e. circadian rhythms in aqueous humor dynamics. Based on what the investigators know of 24 hour IOPs this drug is expected to work well at night potentially by enhancing uveoscleral outflow. This study will test this hypothesis.
This single-center, investigator-masked, crossover study is designed to investigate the circadian rhythms of aqueous humor dynamics in human subjects with ocular hypertension (OHT) before and after intervention with a commonly used ocular hypotensive medication, brimonidine. Thirty participants with ocular hypertension (intraocular pressure greater than 20mmHg) will be enrolled.
The subjects will undergo a baseline phase and medication phase using brimonidine. At both phases, they will attend a daytime and a nighttime study visit in which fluorophotometry will be used to calculate aqueous flow (production), trabecular outflow facility, and uveoscleral outflow. At the completion of the study, subjects will return to their previous ophthalmic clinic.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intraocular pressure lowering drug | Active comparator | Drug: BrimonidineEyedrops for lowering intraocular pressure |
| Artificial Tears | Placebo comparator | Drug: Artificial tearsLubricated eye drops |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Subjects must be 19 years of age or older
- Subjects must exhibit a history of untreated IOPs between 21 and 35 mmHg (inclusive)
Key exclusion criteria (23 listed)
- Age less than nineteen years old
- Women who are pregnant, lactating or of childbearing potential who are not using birth control measures.
- Aphakia or pseudophakia
- Best corrected visual acuity worse than 20/60 in either eye
- Chronic or recurrent severe ocular inflammatory disease
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 |
|---|---|---|
| BrimonidineAlso: Mirvaso, Alphagan POne drop of brimonidine in each eye three times a day for six weeks. | Drug | Intraocular pressure lowering drug |
| Artificial tearsAlso: SystaneLubricating drops added three times a day for six weeks | Drug | Artificial Tears |
Primary outcome
Seated Day-time IOP 9 am and 11 am, Supine Day-time IOP 9 am and 11 am, and Seated Night-time IOP 9 pm and 11 pm
Time frame: 6 weeks
Seated day-time and supine day-time IOP was measured by pneumatonometer at 9 am and 11 am. Seated night-time IOP was measured at 9 pm and 11 pm.
Supine Night-time & Day-time Seated Episcleral Venous Pressure (EVP)
Time frame: 6 weeks plus 2 days
The episcleral venous pressure was measured using the episcleral venomanometer
3 secondary outcomes
Aqueous Flow
Time frame: 6 weeks
Uveoscleral Outflow
Time frame: 6 weeks
Outflow Facility
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24886701Fan S, Agrawal A, Gulati V, Neely DG, Toris CB. Daytime and nighttime effects of brimonidine on IOP and aqueous humor dynamics in participants with ocular hypertension. J Glaucoma. 2014 Jun-Jul;23(5):276-81. doi: 10.1097/IJG.0000000000000051.
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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.
Carol B Toris, PhD principal investigator
Research Instructor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Brimonidine and Artificial tears in people with Intraocular Pressure, run by University of Nebraska at 1 site in United States.
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 23 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 28 Nov 2023. 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 United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Seated Day-time IOP 9 am and 11 am, Supine Day-time IOP 9 am and 11 am, and Seated Night-time IOP 9 pm and 11 pm (time frame: 6 weeks). The study lists 2 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 NCT01144494, 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 28 Nov 2023; AzTrials last refreshed its copy on 27 Oct 2026.