A Randomized Study Evaluating the Efficacy and Safety of Timolol Ophthalmic Solution as an Acute Treatment of Migraine
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|ClinicalTrials.gov Identifier: NCT03836664|
Recruitment Status : Completed
First Posted : February 11, 2019
Results First Posted : July 2, 2019
Last Update Posted : July 2, 2019
|Condition or disease||Intervention/treatment||Phase|
|Migraine||Drug: Timolol Drug: Placebo||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|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|
|Actual Study Start Date :||February 27, 2017|
|Actual Primary Completion Date :||April 14, 2018|
|Actual Study Completion Date :||April 14, 2018|
Experimental: Group 1: Timolol
Participants will be given 0.5% timolol ophthalmic solution to use after migraine onset. Participants will put 2 drops of solution in each eye after migraine and then again 2 hours later.
Timolol is a clear solution supplied in a plastic ophthalmic dispenser.
Placebo Comparator: Group 2: Placebo
Participants will be given matching placebo (0.9% normal saline solution) to use after migraine onset. Participants will put 2 drops of solution in each eye after migraine and then again 2 hours later.
Placebo is normal saline solution that will be supplied in container matched to Timolol container.
Other Name: inactive drug
- Headache Severity [ Time Frame: Headache/ pain severity at onset and at 120 minutes post intervention use ]Measure of the change in severity using visual analogue pain scale ranging from 0-10 with zero being no pain and ten being worst pain. Scale will be completed after each migraine episode over course of participation in study, up to 8 weeks.
- Adverse Reaction From Using Timolol Eye Drops [ Time Frame: 8 weeks ]Measured by number of adverse events experienced by the participants from the intervention. Each adverse event was counted as one.
- Number of Participants Satisfied With Intervention [ Time Frame: 8 weeks ]Measured by patient-reported satisfaction questionnaire. Satisfaction level was looked at as "satisfactory and very satisfactory" compared to "neutral and unsatisfied".
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03836664
|United States, Kansas|
|University of Kansas Medical Center|
|Kansas City, Kansas, United States, 66160|
|Principal Investigator:||Dipika Aggarwal, MD||University of Kansas Medical Center|