A Randomized Study Evaluating the Efficacy and Safety of Timolol Ophthalmic Solution as an Acute Treatment of Migraine

Migraine Clinical Trial

Official title: A Randomized, Double-Blinded, Placebo-Controlled, Cross Over Study Evaluating the Efficacy and Safety of Timolol Ophthalmic Solution as an Acute Treatment of Migraine

Status Completed

Clinical Trial Summary

The purpose of this study is to assess the efficacy (headache freedom at 2 hours) of Timolol 0.5% ophthalmic solution compared to placebo in acute treatment of migraine headache. And to assess the safety and tolerability of Timolol 0.5% ophthalmic solution in treatment of acute migraine headache.

Clinical Trial Description

Oral beta-blockers are a class of medications frequently used to control blood pressure, angina, and heart irregularities. Certain oral beta-blockers such as propranolol and timolol are used on a daily basis to prevent migraines. However, propranolol and timolol tablets have not been shown to be effective as an acute treatment to stop attacks of migraine because of their longer onset of action. We propose that, since beta-blocker eye drops, unlike tablets are quickly absorbed through the covering of the eye and lining of the nose and can be detected in the bloodstream within minutes, can be beneficial and efficacious in the treatment of headache abortion.

Timolol is a non-selective beta-adrenoreceptor antagonist. Oral timolol (20-30 mg daily) has been studied in 3 randomized controlled trials and have been found to reduce headache frequency by more than 50% when compared to placebo. It has been approved by FDA for prophylactic use in migraine patients and had level A evidence to support this indication. The prophylactic benefit of beta-blockers in migraine treatment is not completely understood. It may be related to the effect of beta-blockers on central autonomic vascular tone center, which in turn modulate the cerebrovascular reactivity to sensory stimulation.Propranolol, a beta-adrenergic blocker modulates serotonergic transmission, regulates peri aqueductal pathway activation and prevents central sensitization, normalizes neuronal excitability in the CNS, and blocks cortical spreading depression (CSD). Topical ocular beta blockers have been reported to be successful in retinal arteriolar spasm, retinal migraines causing visual field defects, migraines causing oculomotor nerve palsy, and as abortive agents in migraine patients. Topical timolol maleate solution 0.5% reaches a concentration of 0.5 ng/ml in the plasma within 4 hours of first dose after being used twice daily for 7 days.

Topical beta-blockers so far have been noted to be effective for acute migraine episodes only in case reports. We believe that this pilot study, to evaluate the efficacy and safety of a timolol eye drop for acute treatment of migraine headaches, will open doors for future trials and larger studies. If successful, this will be able establish the use of beta-blocker eye drops which is a simple, painless and low cost acute treatment of migraine.

The aim of this study is to determine the efficacy of timolol eye drops for the acute treatment of migraine. ;

Related Conditions & MeSH terms

• Migraine
• Migraine Disorders

• NCT number: NCT03836664
• Study type: Interventional
• Source: University of Kansas Medical Center
• Status: Completed
• Phase: Phase 2
• Start date: February 27, 2017
• Completion date: April 14, 2018