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Effect of Cosopt Versus Combigan on Retinal Vascular Autoregulation in Primary Open Angle Glaucoma (POAG)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier:
NCT00824824
First received: January 16, 2009
Last updated: October 27, 2016
Last verified: October 2012
Results First Received: August 30, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Basic Science
Condition: Glaucoma
Interventions: Drug: Dorzolamide 2%-timolol 0.5%
Drug: Brimonidine 0.2%-0.5% timolol 0.5

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 21 primary open angle glaucoma patients were recruited for the study from the practices of Douglas J. Rhee, Angela V. Turalba, and Louis R. Pasquale at Massachusetts Eye and Ear Infirmary, Boston. Recruitment took place between February 13, 2009 and December 21, 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Prior to the initial testing visit, subjects ceased using their current IOP-lowering medications and were run in for 6 weeks on timolol 0.5% BID OU. After this 6 week period baseline measurements were taken and 7 were identified with retinal vascular dysregulation. These 7 patients were then randomized into one of two treatment arms.

Reporting Groups
  Description
Dorzolamide-Timolol Then Brimonidine-Timolol 4 of the 7 POAG subjects with RVD were randomized into the dorzolamide hydrochloride 2% - timolol 0.5% ophthalmic solution. The 4 subjects received this treatment for 6 weeks. After the 6-week period the same measurements that were taken at baseline where taken once again. After these measurements were collected these 4 subjects were treated with brimonidine tartrate 0.2%-timolol maleate 0.5% ophthalmic solution for 6 weeks. After this second 6 week period the same measurements that were taken previously were taken again.
Brimonidine-Timolol Then Dorzolamide-Timolol 3 of the 7 POAG RVD subjects were ransomized into the brimonidine tartrate 0.2%-timolol maleate 0.5% ophthalmic solution. The 3 subjects received this treatment for 6 weeks. After the 6-week period the same measurements that were taken at baseline where taken once again. After these measurements were collected these 3 subjects were treated with dorzolamide hydrochloride 2% - timolol 0.5% ophthalmic solution for 6 weeks.After this second 6 week treatment period the same measurements where taken again.

Participant Flow:   Overall Study
    Dorzolamide-Timolol Then Brimonidine-Timolol   Brimonidine-Timolol Then Dorzolamide-Timolol
STARTED   4   3 
COMPLETED   4   3 
NOT COMPLETED   0   0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
There are 14 subjects in this study whop have PAOG without RVD. There are 7 subjects with POAG with RVD. The 14 subjects without RVD did not continue in the two treament arms of this study.

Reporting Groups
  Description
Primary Open Angle Glaucoma Subjects of either gender with age range 40 to 80 years old with POAG were eligible for the study. Eligible subjects had a history of an untreated IOP > 21 mmHg in the left eye and a CPSD ≥ 1.0 in this eye. Patients being treated with more than two IOP lowering medications concurrently were excluded. All eligible subjects had open angles on gonioscopy with the filtering portion of the trabecular meshwork visible for 360° in both eyes. All subjects also had at least two reliable Humphrey 24-2 full threshold visual fields that showed reproducible loss in the left eye on tests with fixation loss ≤33%, false positives ≤ 20% and false negatives ≤ 20%. Patients with evidence of exfoliation or pigment dispersion syndrome in either eye were excluded. Subjects with diabetic retinopathy or a history of ocular laser or incisional surgery in either eye were also excluded.
POAG With RVD 7 subjects with POAG were identified to have retinal vascular dysregulation (RVD). We determined whether RVD was present in the following way. The percentage change between the retinal blood flow measured while reclining for 30 min and the baseline retinal blood flow measured while seated was calculated. In a previous study, we found that among healthy subjects the change in the retinal blood flow while reclining compared to sitting was +6.5% ± 12%. For this study, we defined the normal range of blood flow autoregulation as ±2 standard deviations about the mean percentage change found in the control group in our previous study. Subjects with a change in retinal blood flow induced by posture change outside of -17.5% to +35.5% where considered to have RVD.
Total Total of all reporting groups

Baseline Measures
   Primary Open Angle Glaucoma   POAG With RVD   Total 
Overall Participants Analyzed 
[Units: Participants]
 14   7   21 
Age 
[Units: Years]
Mean (Standard Deviation)
 64.5  (8.2)   60.0  (8.6)   63  (8.3) 
Gender 
[Units: Participants]
     
Female   3   2   5 
Male   11   5   16 
Race (NIH/OMB) 
[Units: Participants]
     
American Indian or Alaska Native   0   0   0 
Asian   0   0   0 
Native Hawaiian or Other Pacific Islander   0   0   0 
Black or African American   1   0   1 
White   13   7   20 
More than one race   0   0   0 
Unknown or Not Reported   0   0   0 
Region of Enrollment 
[Units: Participants]
     
United States   14   7   21 


  Outcome Measures

1.  Primary:   Presence of Retinal Vascular Dysregulation (RVD)   [ Time Frame: 6 weeks post treatment ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
A potential limitation of this study is that no washout period occurred because the 6-week treatment periods extended beyond the typical 2-week washout period for dorzolamide and the 3-week washout period for brimonidine.


  More Information
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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
e-mail: Louis_Pasquale@meei.harvard.edu


Publications:

Responsible Party: Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier: NCT00824824     History of Changes
Other Study ID Numbers: 08-12-057
Study First Received: January 16, 2009
Results First Received: August 30, 2012
Last Updated: October 27, 2016
Health Authority: United States: Institutional Review Board