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CompletedNCT01144494BrimonidineUpdated Nov 28, 2023Results posted

Aqueous Humor Dynamics and Brimonidine

An Early Phase 1 interventional study of Brimonidine and Artificial tears in Intraocular Pressure, sponsored by University of Nebraska. Completed at 1 site in United States. Open to participants aged 19 Years and older. Per ClinicalTrials.gov, last updated 2023-11-28.

Sponsored by University of Nebraska · Early Phase 1, Interventional, and Treatment

Phase
Early Phase 1
Study type
Interventional
Enrollment
35
Allocation
Randomized
Ages
19 Years and older
Sex
All
01

Study 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 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.

02

Conditions studied

  • Intraocular Pressure

Keywords

  • Aqueous Humor Dynamics
  • Aqueous Humor Dynamics and Circadian Rhythms
03

In context

Lead sponsor

University of Nebraska is the lead sponsor of 473 studies on the registry; 66 are open to participants now.

Of its 75 completed or terminated interventional studies of FDA-regulated products, 46 (61%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
19 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Subjects must be 19 years of age or older
  • Subjects must exhibit a history of untreated IOPs between 21 and 35 mmHg (inclusive)

Exclusion criteria

Exclusion Criteria:

  • 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.
  • 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.
05

Study design

Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
35 participants (actual)

Study arms

  • Active comparator
    Intraocular pressure lowering drug

    Eyedrops for lowering intraocular pressure

    Drug: Brimonidine

  • Placebo comparator
    Artificial Tears

    Lubricated eye drops

    Drug: Artificial tears

Interventions

  • DrugBrimonidine

    One drop of brimonidine in each eye three times a day for six weeks.

    Also known as: Mirvaso, Alphagan P

  • DrugArtificial tears

    Lubricating drops added three times a day for six weeks

    Also known as: Systane

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 6 weeks

  2. Supine Night-time & Day-time Seated Episcleral Venous Pressure (EVP)

    The episcleral venous pressure was measured using the episcleral venomanometer

    Time frame: 6 weeks plus 2 days

Secondary outcomes

  1. Aqueous Flow

    Measured by fluorophotometry during the day and night on 29 participants.

    Time frame: 6 weeks

  2. 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.

    Time frame: 6 weeks

  3. 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.

    Time frame: 6 weeks

07

Results

Posted Apr 24, 2019

Participant flow

Participant flow — Overall Study
MilestoneIOP Lowering Drug Then Art TearsArtificial Tears Then IOP Lowering Drug
Started1518
Completed1514
Not completed04

Outcome measures

PrimarySeated 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.

Time frame:
6 weeks
Reported as:
Mean · mmHg
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
mmHgIntraocular Pressure Lowering DrugArtificial Tears
Seated day-time 9 am18.1 ± 0.720.3 ± 0.7
Seated day-time 11 am18.0 ± 0.719.9 ± 0.8
Supine day-time 9 am23.1 ± 0.725.4 ± 0.7
Supine day-time 11 am23.1 ± 0.724.7 ± 0.8
Seated night-time 9 pm16.0 ± 0.618.0 ± 0.7
Seated night-time 11 pm16.7 ± 0.718.4 ± 0.7
PrimarySupine Night-time & Day-time Seated Episcleral Venous Pressure (EVP)

The episcleral venous pressure was measured using the episcleral venomanometer

Time frame:
6 weeks plus 2 days
Reported as:
Mean · mmHg
Supine Night-time & Day-time Seated Episcleral Venous Pressure (EVP)
mmHgIntraocular Pressure Lowering DrugArtificial Tears
Daytime Seated10.3 ± 0.210.3 ± 0.2
Nighttime Supine11.3 ± 0.311.2 ± 0.2
SecondaryAqueous Flow

Measured by fluorophotometry during the day and night on 29 participants.

Time frame:
6 weeks
Reported as:
Mean · µl/min
Aqueous Flow
µl/minIOP Lowering DrugArtificial Tears
day-time measurement2.4 ± 0.12.3 ± 0.1
night-time measurement1.5 ± 0.11.5 ± 0.1
SecondaryUveoscleral 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.

Time frame:
6 weeks
Reported as:
Mean · μL/min
Uveoscleral Outflow
μL/minIOP Lowering DrugArtificial Tears
Uveoscleral Outflow0.84 (0.24 to 1.46)0.72 (0.11 to 1.34)
SecondaryOutflow 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.

Time frame:
6 weeks
Reported as:
Mean · μL/min
Outflow Facility
μL/minIOP Lowering Drug (Day)IOP Lowering Drug (Night)Artificial Tears (Day)Artificial Tears (Night)
Outflow Facility0.28 ± 0.020.28 ± 0.020.29 ± 0.020.29 ± 0.02

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Intraocular Pressure Lowering Drug—0/33 (0%)0/33 (0%)
Artificial Tears—0/33 (0%)4/33 (12.1%)
Most frequent other events
Most frequent other events
EventIntraocular Pressure Lowering DrugArtificial Tears
Acute anterior uveitisEye disorders0/333/33
IOP equal to 35mmHgEye disorders0/331/33
Corneal EpitheliopathyEye disorders0/331/33

Baseline characteristics

Intraocular pressure, episcleral venous pressure, and aqueous flow were calculated using data from 29 participants. However, tonography/outflow facility data on 2 participants were not reliable, therefore uveosleral outflow and outflow facility analysis were performed on 27 participants.

Age, Continuous
Age, Continuous(years)All Study Participants
Mean58.6 ± 1.7
Sex: Female, Male
Sex: Female, Male(Participants)All Study Participants
Female19
Male10
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)All Study Participants
White21
African American6
Hispanic1
Native American1
Region of Enrollment
Region of Enrollment(participants)All Study Participants
United States29
08

Study locations

1 site
  • University of Nebraska Medical Center
    Omaha, Nebraska 68198-5540, United States
09

References and documents

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 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 28, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01144494
Lead sponsor
University of Nebraska
Responsible party
Sponsor
First posted
Jun 15, 2010
Start date
Aug 1, 2010
Primary completion
Oct 1, 2011
Completion
Oct 1, 2011
Results posted
Apr 24, 2019
Last update
Nov 28, 2023

Study contacts

Carol B Toris, PhD
principal investigator · Research Instructor

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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