The Diurnal and Nocturnal Effect of Pilocarpine on Intraocular Pressure and Ocular Perfusion Pressure

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT02754570
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arm: 1
• Duration (Months): 19.7
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The aim of this study will be to determine the effects of pilocarpine as an adjunct medication to latanoprost monotherapy at multiple intervals throughout a 24-hour period and compare these effects to latanoprost alone.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma, Open-angle; Hypertension, Ocular	Drug: Pilocarpine	N/A

Detailed Description

This study plans to learn more about the effect of pilocarpine on intraocular pressure and ocular perfusion pressure for a full twenty-four hour period.

In this study, the investigators seek to better characterize the knowledge base of the intraocular pressure (IOP) lowering effects of pilocarpine in patients with open angle glaucoma or ocular hypertension who are currently taking latanoprost. The goal is to define the potential additive effect of pilocarpine throughout a 24-hour period, not only for IOP, but for ocular perfusion pressure (defined as 2/3[diastolicBP + 1/3(systolicBP - diastolicBP)] - IOP). These data will allow to expand current knowledge of the effects of pilocarpine and help determine if this medication has a useful role as an adjunctive treatment in glaucoma.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Diurnal and Nocturnal Effect of Pilocarpine on Intraocular Pressure and Ocular Perfusion Pressure
• Study Start Date: Jul 1, 2016
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Feb 21, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pilocarpine group Subjects with open-angle glaucoma and ocular hypertension that are currently taking latanoprost	Drug: Pilocarpine; Pilocarpine will be administered 4 times in addition to latanoprost.; Other Names: Pilocarpine Hydrochloride

Outcome Measures

Primary Outcome Measures

1. Change in Intraocular Pressure From Baseline at Visit 3 [Two 24-hour visits: Baseline/Visit 2; Up to week 4/Visit 3]

   Subjects will be enrolled at the first visit. Patients already on latanoprost may proceed immediately with the second visit. Patients on a different prostaglandin analog medication will be switched to latanoprost for at least 6 weeks. At second visit, intraocular pressure and blood pressure will be measured every 2 hours for a 24-hour period. At any point over the next 4 weeks, another 24-hour visit will be performed. This time, a dose of pilocarpine 2% will be administered at 4 different times in addition to the latanoprost . As before, intraocular pressure and blood pressure will be measured every 2 hours. After visit 3, subjects will return to their prior treatment regimen. Change in the intraocular pressure from the second and the third visit will be determined. 8 diurnal readings and 4 nocturnal readings were averaged separately during both Visit 2 for the PGA Monotherapy and Visit 3 for Pilocarpine+PGA

Secondary Outcome Measures

1. Change in Ocular Perfusion Pressure [Two 24-hour visits: Baseline/Visit 2; Up to week 4/Visit 3]

   Ocular perfusion pressure will calculated from the intraocular pressure and blood pressure measurements. At Baseline/Visit 2, intraocular pressure and blood pressure will be measured every 2 hours for a 24-hour period. At any point over the next 4 weeks, another 24-hour visit (Visit 3) will be performed. This time, a dose of pilocarpine 2% will be administered at 4 different times in addition to the latanoprost (PGA monotherapy). As before, intraocular pressure and blood pressure will be measured every 2 hours. 8 diurnal readings and 4 nocturnal readings were averaged separately during both Visit 2 for the PGA Monotherapy and Visit 3 for Pilocarpine+PGA

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 89 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Current confirmed diagnosis of:

• open angle glaucoma, or

• ocular hypertension including pigment dispersion glaucoma, and

• pseudoexfoliation glaucoma.

• Current use of topical latanoprost once a day in both eyes for at least 6 weeks

• any race/ethnicity

Exclusion Criteria:

• Females who are currently pregnant or planning to become pregnant during the study period

• Diagnosis of any other form of glaucoma other than open-angle

• Intraocular pressure readings of <14mmHg in either eye when measured during routine office visit in the past 12 months.

• Schaffer angle grade < 2 in either eye by gonioscopy

• Intraocular surgery within 6 months or laser within 3 months

• History of retinal tear or detachment in either eye

• Active iritis in either eye as determined by most recent eye examination

• Patients who smoke or have irregular daily sleep patterns

• Patients who have started or changed glucocorticoids therapy in the last 3 months

• Patients who are currently using medical or recreational marijuana

• Any use of a non-FDA approved medication for glaucoma in the last 3 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Denver Eye Hospital	Denver	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver

Investigators

• Principal Investigator: Leonard Seibold, MD, University of Colorado, Denver

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 10, 2017

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02754570
• Other Study ID Numbers: 15-1972; UL1TR001082
• First Posted: Apr 28, 2016
• Last Update Posted: Nov 7, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of Colorado, Denver: Open-angle glaucoma; Ocular hypertension; Latanoprost; Pilocarpine
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Pilocarpine

Study Results

Participant Flow

Arm/Group Title	Pilocarpine Group
Arm/Group Description	Subjects with open-angle glaucoma and ocular hypertension. Pilocarpine: Pilocarpine will be administered 4 times in addition to latanoprost.
Period Title: Overall Study
STARTED	27
Visits 1 and 2 (PGA Only)	27
Visit 3 (PGA + Pilocarpine)	27
COMPLETED	27
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Pilocarpine Group
Arm/Group Description	Subjects with open-angle glaucoma and ocular hypertension. Pilocarpine: Pilocarpine will be administered 4 times in addition to latanoprost.
Overall Participants	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.3 (10.8)
Sex: Female, Male (Count of Participants)
Female	20 74.1%
Male	7 25.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 7.4%
Not Hispanic or Latino	25 92.6%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 18.5%
White	19 70.4%
More than one race	0 0%
Unknown or Not Reported	2 7.4%
Region of Enrollment (participants) [Number]
United States	27 100%
Diagnosis (Count of Participants)
Primary Open Angle Glaucoma	21 77.8%
Ocular Hypertension	4 14.8%
Pseudoexfoliation Glaucoma	2 7.4%
Lens Status (Count of Participants)
Phakic	19 70.4%
Pseudophakic	8 29.6%
Prior Laser Surgery (Count of Participants)
Laser Peripheral Iridotomy	5 18.5%
Selective Laser Trabeculoplasty	3 11.1%
No Prior Laser	19 70.4%

Outcome Measures

1. Primary Outcome

Title	Change in Intraocular Pressure From Baseline at Visit 3
Description	Subjects will be enrolled at the first visit. Patients already on latanoprost may proceed immediately with the second visit. Patients on a different prostaglandin analog medication will be switched to latanoprost for at least 6 weeks. At second visit, intraocular pressure and blood pressure will be measured every 2 hours for a 24-hour period. At any point over the next 4 weeks, another 24-hour visit will be performed. This time, a dose of pilocarpine 2% will be administered at 4 different times in addition to the latanoprost . As before, intraocular pressure and blood pressure will be measured every 2 hours. After visit 3, subjects will return to their prior treatment regimen. Change in the intraocular pressure from the second and the third visit will be determined. 8 diurnal readings and 4 nocturnal readings were averaged separately during both Visit 2 for the PGA Monotherapy and Visit 3 for Pilocarpine+PGA
Time Frame	Two 24-hour visits: Baseline/Visit 2; Up to week 4/Visit 3

Outcome Measure Data

Analysis Population Description

Patients who are using a prostaglandin analog (PGA) will be monitored at visit two. At visit 3, pilocarpine will be added four times per day to the PGA therapy.

Arm/Group Title	Pilocarpine Group
Arm/Group Description	Subjects with open-angle glaucoma, ocular hypertension or pseudoexfoliation glaucoma. Pilocarpine: Pilocarpine will be administered 4 times in addition to latanoprost or brimonidine
Measure Participants	27
Visit 2: Nocturnal PGA	21.1 (0.7)
Visit 2: Diurnal PGA	18.2 (0.5)
Visit 3: Nocturnal PGA	20.0 (0.6)
Visit 3: Diurnal PGA	17.1 (0.4)

2. Secondary Outcome

Title	Change in Ocular Perfusion Pressure
Description	Ocular perfusion pressure will calculated from the intraocular pressure and blood pressure measurements. At Baseline/Visit 2, intraocular pressure and blood pressure will be measured every 2 hours for a 24-hour period. At any point over the next 4 weeks, another 24-hour visit (Visit 3) will be performed. This time, a dose of pilocarpine 2% will be administered at 4 different times in addition to the latanoprost (PGA monotherapy). As before, intraocular pressure and blood pressure will be measured every 2 hours. 8 diurnal readings and 4 nocturnal readings were averaged separately during both Visit 2 for the PGA Monotherapy and Visit 3 for Pilocarpine+PGA
Time Frame	Two 24-hour visits: Baseline/Visit 2; Up to week 4/Visit 3

Outcome Measure Data

Analysis Population Description

Patients who are using a prostaglandin analog (PGA) will be monitored at visit two. At visit 3, pilocarpine will be added four times per day to the PGA therapy.

Arm/Group Title	Pilocarpine Group
Arm/Group Description	Subjects with open-angle glaucoma, ocular hypertension or psuedoexfoliation glaucoma. Pilocarpine: Pilocarpine will be administered 4 times in addition to latanoprost.
Measure Participants	27
Visit 2: Diurnal Ocular Perfusion Pressure	44.12 (1.2)
Visit 2: Nocturnal Ocular Perfusion Pressure	37.2 (1.3)
Visit 2: Diurnal Systolic Blood Pressure	132.5 (2.8)
Visit 2: Nocturnal Systolic Blood Pressure	125.8 (2.9)
Visit 3: Diurnal Ocular Perfusion Pressure	44.3 (1.1)
Visit 3: Nocturnal Ocular Profusion Pressure	37.1 (1.2)
Visit 3: Diurnal Systolic Blood Pressure	130.8 (2.9)
Visit 3: Nocturnal Systolic Blood Pressure	122.7 (2.9)

Adverse Events

Time Frame	1 month
Arm/Group Title	Pilocarpine Group		PGA Monotherapy
Arm/Group Description	Subjects with open-angle glaucoma, ocular hypertension or pseudoexfoliation glaucoma. Pilocarpine: Pilocarpine will be administered 4 times in addition to latanoprost.		Subjects with open-angle glaucoma, ocular hypertension or pseudoexfoliation glaucoma. PGA: Latanoprost or Bimatoprost administered one time per day.
All Cause Mortality
	Pilocarpine Group		PGA Monotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)
Serious Adverse Events
	Pilocarpine Group		PGA Monotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Pilocarpine Group		PGA Monotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)

Limitations/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.