Effect of Alphagan on Retinal Blood Flow Autoregulation and Motion Detection in Patients With Normal Pressure Glaucoma

• Sponsor: Massachusetts Eye and Ear Infirmary
• Information provided by (Responsible Party): Louis Pasquale, MD, Massachusetts Eye and Ear Infirmary

Study Type	Interventional
Study Design	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Glaucoma
Intervention	Drug: brimonidine 0.15%
Enrollment	46

Participant Flow

Recruitment Details
Pre-assignment Details	46 participants enrolled but only 23 had retinal vascular dysregulation.

Arm/Group Title	Patients With RVD
Arm/Group Description	Patients who exhibited retinal vascular dysregulation at the initial visit. Intervention: brimonidine 0.15% three times per day for 8 weeks. Alphagan (brimonidine) 0.15%: One drop in each eye three times a day for 8 weeks.
Period Title: Overall Study
Started	23
Completed	17
Not Completed	6
Reason Not Completed
Adverse Event	5
Technical Problems	1

Baseline Characteristics

Arm/Group Title		Patients With RVD
Arm/Group Description		Patients who exhibited retinal vascular dysregulation at the initial visit. Intervention: brimonidine 0.15% three times per day for 8 weeks. Alphagan (brimonidine) 0.15%: One drop in each eye three times a day for 8 weeks.
Overall Number of Baseline Participants		23
Baseline Analysis Population Description		[Not Specified]
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	23 participants
		57.1 (10.8)
		[1] Measure Description: age range: 35 years to 80 years
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants
	Female	12 52.2%
	Male	11 47.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	23 participants
		23

Outcome Measures

1. Primary Outcome

Title	Presence of Retinal Blood Flow Autoregulation
Description	We defined retinal vascular dysregulation based on the percentage change between the retinal blood flow measured while reclining for 30 minutes and the baseline seated measures. In a prior study, we found that healthy subjects exhibited a +6.5%±12% blood flow change induced by 30 minutes of reclining. Thus, we defined the normal range of blood flow autoregulation as within 2 standard deviations of the mean percentage change found in this group, or -17.5% to +30.5%.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Patients With RVD
Arm/Group Description:	Patients who exhibited retinal vascular dysregulation at the initial visit. Intervention: brimonidine 0.15% three times per day for 8 weeks. Alphagan (brimonidine) 0.15%: One drop in each eye three times a day for 8 weeks.
Overall Number of Participants Analyzed	17
Measure Type: Number; Unit of Measure: participants
	14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Patients With RVD
	Comments	There would be no change in retinal vascular dysregulation after treatment with brimonidine
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Chi-squared, Corrected
	Comments	[Not Specified]

2. Secondary Outcome

Title	Frequency Doubling Perimetry
Description	Frequency doubling perimetry was measured pre- and post treatment with brimonidine for 8 weeks.We used the full-threshold N-30 protocol to determine the visual field mean deviation, pattern standard deviation, and test duration in the eye that had hemodynamic testing. The results that are reported below are the mean deviation values recorded as part of the frequency doubling perimetry as these are the most significant.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RVD Patients Pre-brimonidine Treatment	RVD Patients Post-brimonidine Treatment
Arm/Group Description:	Patients who exhibited retinal vascular dysregulation at the initial visit. The mean deviation frequency doubling perimetry values were measured in these patients before their treatment with brimonidine.	Patients who exhibited retinal vascular dysregulation at the initial visit. The mean deviation frequency doubling perimetry values were measured in these patients after their treatment with brimonidine.
Overall Number of Participants Analyzed	17	17
Mean (Standard Deviation); Unit of Measure: dB
	-2.03 (3.50)	-2.77 (5.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVD Patients Pre-brimonidine Treatment
	Comments	A paired t-test was used to determine if their was a statistically significant difference between the mean deviation of the frequency doubling perimetry in the RVD patients pre and post brimonidine treatment.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.28
	Comments	[Not Specified]
	Method	paired t-test
	Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Patients With RVD
Arm/Group Description	Patients who exhibited retinal vascular dysregulation at the initial visit. Intervention: brimonidine 0.15% three times per day for 8 weeks. Alphagan (brimonidine) 0.15%: One drop in each eye three times a day for 8 weeks.
All-Cause Mortality
	Patients With RVD
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Patients With RVD
	Affected / at Risk (%)
Total	0/23 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Patients With RVD
	Affected / at Risk (%)
Total	5/23 (21.74%)
Eye disorders
Allergic reaction *	5/23 (21.74%)
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.

Results Point of Contact

Name/Title: Louis R. Pasquale, MD

Organization: Massachusetts Eye and Ear Infirmary

Phone: 617-573-4270

EMail: Louis_Pasquale@meei.harvard.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Feke GT, Bex PJ, Taylor CP, Rhee DJ, Turalba AV, Chen TC, Wand M, Pasquale LR. Effect of brimonidine on retinal vascular autoregulation and short-term visual function in normal tension glaucoma. Am J Ophthalmol. 2014 Jul;158(1):105-112.e1. doi: 10.1016/j.ajo.2014.03.015. Epub 2014 Apr 5.

Responsible Party:	Louis Pasquale, MD, Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier:	NCT01105065 History of Changes
Other Study ID Numbers:	10-03-019 (75643)
First Submitted:	April 14, 2010
First Posted:	April 16, 2010
Results First Submitted:	December 7, 2014
Results First Posted:	October 27, 2016
Last Update Posted:	April 4, 2017