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

Study Overview
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Brief Summary
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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.

Official Title
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The Effect of Dronabinol on Ocular Hemodynamics in Patients With Primary

Conditions
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Retinal Blood Flow

Intervention / Treatment
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* Drug: Dronabinol 5 MG
* Drug: Dronabinol 10 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 Regular consumption of cannabis and inability to not consume cannabis during the study period Symptoms of a clinically relevant illness in the 3 weeks before the first study day History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with distribution, metabolism or excretion of study drugs Blood donation during the previous 3 weeks Known hypersensitivity to any of the components of the IMP under investigation or other study medication History or family history of epilepsy Pregnant or breast-feeding women Women of childbearing potential (neither menopausal, nor hysterectomized, nor sterilized) not using effective contraception (oral contraceptives, intra-uterine device, contraceptive implant or condoms)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: healthy subjects<br> | Drug: Dronabinol 5 MG<br>* oral administration<br>Drug: Dronabinol 10 MG<br>* oral administration<br>Drug: Placebo<br>* oral administration<br>|
| Experimental: glaucoma patients<br> | Drug: Dronabinol 5 MG<br>* oral administration<br>Drug: Dronabinol 10 MG<br>* oral administration<br>Drug: Placebo<br>* oral administration<br>|
| Placebo Comparator: healthy volunteers<br> | Drug: Dronabinol 5 MG<br>* oral administration<br>Drug: Dronabinol 10 MG<br>* oral administration<br>Drug: Placebo<br>* oral administration<br>|
| Placebo Comparator: Glaucoma patients<br> | Drug: Dronabinol 5 MG<br>* oral administration<br>Drug: Dronabinol 10 MG<br>* oral administration<br>Drug: Placebo<br>* oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |