Aqueous Humor Dynamic Components That Determine Intraocular Pressure Variance

NCT04412096 | Completed Phase 4 FDA Drug

• 2 other identifiers: 2020H0284R01EY022124
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 3

Brief Summary

Glaucoma is a major cause of blindness. The inability to predict a patient's IOP response to medications is a critical barrier for the clinician to consistently provide highly effective IOP-based treatments. Current trial-and-error approaches to glaucoma management are inefficient and have not addressed this barrier as there are no predictive factors for drug response. Our long-term goal is to improve outcomes by identifying biomarkers and environmental factors that profile a patient at risk for glaucoma by age-of-onset, rate of disease progression, "poor response" to treatment, and large IOP fluctuation. Our purpose of this research project is to address this critical barrier by focusing on physiological factors that predict IOP response to drugs.

Conditions

Glaucoma; OHT - Ocular Hypertension

Keywords

aqueous humor dynamics; glaucoma; eye diseases; timolol; latanoprost; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; neurotransmitter agents; molecular mechanisms of pharmacological action; physiological effects of drugs; anti-arrhythmia agents; anti-hypertensive agents

Outcome Measures

Primary Outcomes (1)

• Variation in eye pressures between individuals

  Eye pressure is a steady state quantitative trait that is measured in mm Hg. Eye pressure is determined by the following physiological factors (units of measure): eye fluid or aqueous humor production (microliters/minute), aqueous humor outflow (microliters/minute), outflow resistance (microliters/minute/mm Hg) and venous pressure (mm Hg) of the eye. All of these physiological factors will be determined under baseline condition and under glaucoma drug treatment.

  measurement after 1 week of treatment

Secondary Outcomes (2)

• Variation in aqueous flow between individuals

  measurement 1 week after treatment

• Variation in episcleral venous pressure

  measurement 1 week after treatment

Study Arms (2)

Timolol 0.5%

EXPERIMENTAL

To compare the variation in response to timolol between individuals

Drug: Timolol 0.5% ophthalmic solution

Latanoprost 0.005%

EXPERIMENTAL

To compare the variation in response to latanoprost between individuals

Drug: Latanoprost 0.005% Ophthalmic Solution

Interventions

Timolol 0.5% ophthalmic solution DRUG

1 drop BID

Timolol 0.5%

Latanoprost 0.005% Ophthalmic Solution DRUG

1 drop QD

Latanoprost 0.005%

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any self-declared ethnicity-race
• Open-angle with one of the following:
• Untreated OHT ≥ 21mmHg
• Treated OHT with history of IOP ≥ 21 mmHg on 2 prior clinic visits or IOP ≥ 21 mmHg at screening
• Mild-to-moderate stage open-angle glaucoma based on history of untreated IOP ≥ 21 mmHg
• Reliable Humphrey visual field test result within previous 1 year
• Open on gonioscopy within previous 1 year
• At least one eye must be phakic
• Able to cooperate for aqueous humor dynamic procedures
• Able to participate on site over the multi-visit study period
• Contact lenses must be removed before topical fluorescein instillation and remain out until study testing the following day is completed.
• Contact lenses must be removed for the entire duration of the study visits.
• All study medication must be used without contact lenses in the eyes.

You may not qualify if:

• Women who are pregnant or breastfeeding
• IOP ≥ 38 in study eye(s) or at discretion of the clinician
• Refusal to remove contact lenses
• Advanced visual field loss (MD ≤ -16 dB) or threat to fixation in study eye(s) or at discretion of the clinician
• Study eye(s) with any sign of Fuchs cornea dystrophy as noted clinically with guttae and corneal edema
• Narrow angle of ≤ Shaffer grade 2 for 180 degrees, peripheral synechiae, or peripheral iridotomy in either eye
• History of acute angle closure crisis in either eye
• History of glaucoma incisional surgery (e.g., trabeculectomy, glaucoma drainage implant, Xen gel stent) in study eye(s)
• History of minimally invasive glaucoma surgery (MIGS, e.g., angle surgery, Cypass) in study eye(s)
• History of any cycloablation surgery (e.g., micropulse or diode transcleral or endoscopic cyclophotocoagulation) in study eye(s)
• Study eye cannot have history of any past SLT or ALT glaucoma laser treatments.
• Study eye(s) cannot have any history of refractive surgery
• Study eye(s) cannot have any history of herpetic infection of the cornea
• Study eye(s) cannot have chronic or recurrent inflammatory eye disease
• Study eye(s) cannot have ocular trauma within the past 6 months, other than uncomplicated cornea abrasion

Sponsors & Collaborators

• Ohio State University: lead
• University of Nebraska: collaborator
• Mayo Clinic: collaborator
• National Eye Institute (NEI): collaborator

Study Sites (3)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68105, United States

Location

The Ohio State University

Columbus, Ohio, 43212, United States

Location

Related Publications (2)

• Man X, Costa R, Ayres BM, Moroi SE. Acetazolamide-Induced Bilateral Ciliochoroidal Effusion Syndrome in Plateau Iris Configuration. Am J Ophthalmol Case Rep. 2016 Oct;3:14-17. doi: 10.1016/j.ajoc.2016.05.003. Epub 2016 May 17.

  PMID: 29226268 BACKGROUND

• Kazemi A, Reitinger JC, Toris CB, Gulati V, Fan S, Reed DM, Moroi SE, Sit AJ. Aqueous Humor Dynamics Changes and Predictors of IOP Response to Latanoprost in Healthy Subjects. J Glaucoma. 2025 Dec 1;34(12):1056-1064. doi: 10.1097/IJG.0000000000002585. Epub 2025 May 9.

  PMID: 40341017 DERIVED

MeSH Terms

Conditions

Glaucoma; Ocular Hypertension; Eye Diseases

Interventions

Timolol; Ophthalmic Solutions; Latanoprost

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Thiadiazoles; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morpholines; Oxazines; Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• Sayoko Moroi, MD, PhD

  Professor and Chair

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chair

Model Details: The overall study design is a prospective, open-label, randomized clinical trial with randomized order of 7-day treatments with timolol followed by a washout period and then with latanoprost or vice versa. Participants will undergo two 7-day treatments, with timolol 0.5% (1 drop two times daily) and latanoprost 0.005% (1 drop daily in the evening). The order of timolol and latanoprost will be randomized. The IOP, AHD parameters and IOP fluctuation will be compared in an individual under three conditions: (i) baseline, and after a randomized order of 7-day treatment of (ii) timolol 0.5% 1 drop two times daily and (iii) latanoprost 0.005% 1 drop in the evening separated by a 6-week washout period. The overall time commitment to complete these procedures is three to four months.

Study Record Dates

• First Submitted: May 29, 2020
• First Posted: June 2, 2020
• Study Start: November 23, 2020
• Primary Completion: May 22, 2025
• Study Completion: May 22, 2025
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)