Aqueous Humor Dynamics and Brimonidine

• Sponsor: University of Nebraska (Other)
• Overall Status: Completed
• CT.gov ID: NCT01144494
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arms: 2
• Actual Duration (Months): 19
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

Investigate nocturnal effects on aqueous humor dynamics of a clinically used eye pressure -lowering drug, brimonidine, when given for six weeks.

Condition or Disease	Intervention/Treatment	Phase
Intraocular Pressure	Drug: Brimonidine; Drug: Artificial tears	N/A

Detailed Description

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 volunteers 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

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Circadian Rhythms of Aqueous Humor Dynamics in Subjects With Ocular Hypertension Using Brimonidine
• Actual Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Intraocular pressure lowering drug Eyedrops for lowering intraocular pressure	Drug: Brimonidine; One drop of brimonidine in each eye three times a day for six weeks.
Placebo Comparator: Artificial Tears Lubricated eye drops	Drug: Artificial tears; Lubricating drops added three times a day for six weeks; Other Names: Systane

Outcome Measures

Primary Outcome Measures

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 [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.

2. Supine Night-time & Day-time Seated Episcleral Venous Pressure (EVP) [6 weeks plus 2 days]

   The episcleral venous pressure was measured using the episcleral venomanometer

Secondary Outcome Measures

1. Aqueous Flow [6 weeks]

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

2. Uveoscleral Outflow [6 weeks]

   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.

3. Outflow Facility [6 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: 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:

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-5540

Sponsors and Collaborators

• University of Nebraska

Investigators

• Principal Investigator: Carol B Toris, PhD, Research Instructor

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Carol B. Toris, BA MS PhD, Principal Investigator, University of Nebraska
• ClinicalTrials.gov Identifier: NCT01144494
• Other Study ID Numbers: 220-10-FB
• First Posted: Jun 15, 2010
• Last Update Posted: May 22, 2019
• Last Verified: May 1, 2019

• Keywords provided by Carol B. Toris, BA MS PhD, Principal Investigator, University of Nebraska: Aqueous Humor Dynamics; Aqueous Humor Dynamics and Circadian Rhythms
• Additional relevant MeSH terms: Brimonidine Tartrate; Lubricant Eye Drops

Study Results

Participant Flow

Pre-assignment Detail	2 subjects consented and then dropped out prior to assignment.

Arm/Group Title	IOP Lowering Drug Then Art Tears	Artificial Tears Then IOP Lowering Drug
Arm/Group Description	Eyedrops for lowering intraocular pressure Brimonidine: One drop of brimonidine in each eye three times a day for six weeks. Lubricated eye drops Artificial tears: Lubricating drops added three times a day for six weeks	Lubricated eye drops Artificial tears: Lubricating drops added three times a day for six weeks Eyedrops for lowering intraocular pressure Brimonidine: One drop of brimonidine in each eye three times a day for six weeks.
Period Title: Overall Study
STARTED	15	18
COMPLETED	15	14
NOT COMPLETED	0	4

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	participants were randomized to receive both IOP lowering drug and lubricating drops in a randomized order
Overall Participants	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.6 (1.7)
Sex: Female, Male (Count of Participants)
Female	19 65.5%
Male	10 34.5%
Race/Ethnicity, Customized (Count of Participants)
White	21 72.4%
African American	6 20.7%
Hispanic	1 3.4%
Native American	1 3.4%
Region of Enrollment (participants) [Number]
United States	29 100%

Outcome Measures

1. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

some patients were consented but did not participate due to various reasons

Arm/Group Title	Intraocular Pressure Lowering Drug	Artificial Tears
Arm/Group Description	Eyedrops for lowering intraocular pressure Brimonidine: One drop of brimonidine in each eye three times a day for six weeks.	Lubricated eye drops Artificial tears: Lubricating drops added three times a day for six weeks
Measure Participants	29	29
Seated day-time 9 am	18.1 (0.7)	20.3 (0.7)
Seated day-time 11 am	18.0 (0.7)	19.9 (0.8)
Supine day-time 9 am	23.1 (0.7)	25.4 (0.7)
Supine day-time 11 am	23.1 (0.7)	24.7 (0.8)
Seated night-time 9 pm	16.0 (0.6)	18.0 (0.7)
Seated night-time 11 pm	16.7 (0.7)	18.4 (0.7)

2. Primary Outcome

Title	Supine Night-time & Day-time Seated Episcleral Venous Pressure (EVP)
Description	The episcleral venous pressure was measured using the episcleral venomanometer
Time Frame	6 weeks plus 2 days

Outcome Measure Data

Analysis Population Description

some patients were consented but did not participate due to various reasons

Arm/Group Title	Intraocular Pressure Lowering Drug	Artificial Tears
Arm/Group Description	Eyedrops for lowering intraocular pressure Brimonidine: One drop of brimonidine in each eye three times a day for six weeks.	Lubricated eye drops Artificial tears: Lubricating drops added three times a day for six weeks
Measure Participants	27	27
Daytime Seated	10.3 (0.2)	10.3 (0.2)
Nighttime Supine	11.3 (0.3)	11.2 (0.2)

3. Secondary Outcome

Title	Aqueous Flow
Description	Measured by fluorophotometry during the day and night on 29 participants.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Measurements were taken in the day and night for each group and analysis was done comparing the difference between and within both groups in the day and night respectively. some patients were consented but did not participate due to various reasons

Arm/Group Title	IOP Lowering Drug	Artificial Tears
Arm/Group Description	Eyedrops for lowering intraocular pressure Brimonidine: One drop of brimonidine in each eye three times a day for six weeks.	Lubricated eye drops Artificial tears: Lubricating drops added three times a day for six weeks
Measure Participants	29	29
day-time measurement	2.4 (0.1)	2.3 (0.1)
night-time measurement	1.5 (0.1)	1.5 (0.1)

4. Secondary Outcome

Title	Uveoscleral Outflow
Description	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

Outcome Measure Data

Analysis Population Description

Tonography/outflow facility data on 2 participants were not reliable, therefore uveosleral outflow analysis was performed on 27 participants. some patients were consented but did not participate due to various reasons

Arm/Group Title	IOP Lowering Drug	Artificial Tears
Arm/Group Description	Eyedrops for lowering intraocular pressure Brimonidine: One drop of brimonidine in each eye three times a day for six weeks.	Lubricated eye drops Artificial tears: Lubricating drops added three times a day for six weeks
Measure Participants	27	27
Mean (95% Confidence Interval) [μL/min]	0.84	0.72

5. Secondary Outcome

Title	Outflow Facility
Description	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

Outcome Measure Data

Analysis Population Description

Tonography/outflow facility data was not reliable in 2 of the participants, therefore analysis was conducted on data from 27 participants. some patients were consented but did not participate due to various reasons

Arm/Group Title	IOP Lowering Drug (Day)	IOP Lowering Drug (Night)	Artificial Tears (Day)	Artificial Tears (Night)
Arm/Group Description	Eyedrops for lowering intraocular pressure Brimonidine: One drop of brimonidine in each eye three times a day for six weeks.	Eyedrops for lowering intraocular pressure Brimonidine: One drop of brimonidine in each eye three times a day for six weeks.	Lubricated eye drops Artificial tears: Lubricating drops added three times a day for six weeks	Lubricated eye drops Artificial tears: Lubricating drops added three times a day for six weeks
Measure Participants	27	27	27	27
Mean (Standard Error) [μL/min]	0.28 (0.02)	0.28 (0.02)	0.29 (0.02)	0.29 (0.02)

Adverse Events

Arm/Group Title	Intraocular Pressure Lowering Drug		Artificial Tears
Arm/Group Description	Eyedrops for lowering intraocular pressure Brimonidine: One drop of brimonidine in each eye three times a day for six weeks.		Lubricated eye drops Artificial tears: Lubricating drops added three times a day for six weeks
All Cause Mortality
	Intraocular Pressure Lowering Drug		Artificial Tears
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Intraocular Pressure Lowering Drug		Artificial Tears
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	Intraocular Pressure Lowering Drug		Artificial Tears
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		4/33 (12.1%)
Eye disorders
IOP equal to 35mmHg	0/33 (0%)		1/33 (3%)
Acute anterior uveitis	0/33 (0%)		3/33 (9.1%)
Corneal Epitheliopathy	0/33 (0%)		1/33 (3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.