The Effect of Dronabinol on Ocular Hemodynamics in Patients With Primary Open Angle Glaucoma

NCT04596826 | Completed Phase 2

• 1 other identifier: OPHT-250719
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

Glaucoma is among the leading causes for irreversible blindness worldwide. While lowering intraocular pressure (IOP) remains the mainstay of therapy, there are still some patients who progress despite well-controlled IOP. There is evidence from several studies that ocular blood flow and its regulation is impaired in patients with glaucoma. Tetrahydrocannabinol (THC) has been used in the treatment for glaucoma in some countries for several years due to its IOP lowering effect. In addition, there is also evidence that THC features neuroprotective effects and improves ocular hemodynamics. Dronabinol is a synthetic THC that is legally available in several European countries. It has the advantage that exact dosing of THC is possible in contrast to previously applied administration forms such as smoking. Due to its legal status in the past, data about the effect of THC on ocular blood flow and its regulation are sparse. In a recent study conducted in the investigators laboratory they found that single administration of dronabinol leads to a significant increase in optic nerve head (ONH) blood flow without impairing its autoregulatory capacity.The aim of the present study therefore is to investigate whether single administration of dronabinol alters optic nerve head (ONH) blood flow in patients with open angle glaucoma. In addition, other parameters for ocular blood flow will be measured, in particular retinal blood flow, retinal oxygen saturation and retinal neurovascular coupling. The study will be conducted in a parallel-group, randomized, double-masked, placebo-controlled, cross-over design. Patients will be randomized to either receive 5mg or 10mg dronabinol on one study day. Other studies investigating retinal hemodynamics or IOP after administration of THC also have used similar or slightly higher doses.

Conditions

Retinal Blood Flow

Outcome Measures

Primary Outcomes (1)

• Optic nerve head blood flow

  To determine the total blood flow in the eye, OCT measurements were performed with a rectangular scanning pattern around the optical nerve head.

  60 minutes on the study day

Other Outcomes (8)

• Flicker induced increase in retinal blood flow using a Fourier Domain Doppler OCT

  30 minutes on the study day

• Retinal vessel diameter (DVA)

  30 minutes on the study day

• Retinal oxygen saturation (DVA)

  30 minutes on the study day

Study Arms (4)

healthy subjects

EXPERIMENTAL

Drug: Dronabinol 5 MG; Drug: Dronabinol 10 MG; Drug: Placebo

glaucoma patients

EXPERIMENTAL

Drug: Dronabinol 5 MG; Drug: Dronabinol 10 MG; Drug: Placebo

healthy volunteers

PLACEBO COMPARATOR

Drug: Dronabinol 5 MG; Drug: Dronabinol 10 MG; Drug: Placebo

Glaucoma patients

PLACEBO COMPARATOR

Drug: Dronabinol 5 MG; Drug: Dronabinol 10 MG; Drug: Placebo

Interventions

Dronabinol 5 MG DRUG

oral administration

Glaucoma patients; glaucoma patients; healthy subjects; healthy volunteers

Dronabinol 10 MG DRUG

oral administration

Glaucoma patients; glaucoma patients; healthy subjects; healthy volunteers

Placebo DRUG

oral administration

Glaucoma patients; glaucoma patients; healthy subjects; healthy volunteers

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of manifest open angle glaucoma as defined as pathological optic disc appearance, glaucoma hemifield test outside normal limits and/or untreated IOP ≥ 21 mmHg on at least three measurements in the medical history.
• Mean deviation in the visual field test \< 10dB
• Informed consent signed and dated
• Patient aged ≥ 18 years old
• Ametropia ≤ 6 diopters
• Normal findings in the medical history and physical examination including ECG unless the investigator considers an abnormality to be clinically irrelevant
• Normal findings in the laboratory testing unless the investigator considers an abnormality to be clinically irrelevant
• Nonsmokers

You may not qualify if:

• Exfoliation glaucoma
• Pigmentary glaucoma
• Secondary glaucoma
• History of acute angle closure
• Intraocular surgery within the last 6 months
• Filtration surgery for glaucoma at any time
• Laser procedure for glaucoma within the last 12 months Visual field not performed or not available within 6 months
• Ocular inflammation or infection within the last 3 months
• Regular use of medication that potentially could interact with THC, abuse of alcoholic beverages or drugs
• History of drug or alcohol abuse
• Psychiatric disorders in the medical history
• Risk for drug dependence as evaluated by a psychiatrist
• Participation in a clinical trial in the 3 weeks preceding the study
• Positive urine drug test at the screening examination or on the study days
• Positive alcohol breath test at the screening examination or on the study days

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Department of Clinical Pharmacology, Medical University Vienna

Vienna, 1090, Austria

Location

Related Publications (1)

• Lindner T, Pai V, Janku P, Hommer N, Hommer A, Abensperg-Traun M, Petric L, Schmetterer L, Garhofer G, Schmidl D. Single oral administration of dronabinol increases ocular blood flow in patients with glaucoma. Acta Ophthalmol. 2025 Aug 7. doi: 10.1111/aos.17573. Online ahead of print.

  PMID: 40772417 DERIVED

MeSH Terms

Interventions

Dronabinol

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Prof. PD Doreen Schmidl, MD, PhD,

Study Record Dates

• First Submitted: October 14, 2020
• First Posted: October 22, 2020
• Study Start: November 11, 2020
• Primary Completion: October 2, 2024
• Study Completion: October 2, 2024
• Last Updated: May 16, 2025

Record last verified: 2023-12

Locations

AU (1)