A Randomized Study Evaluating the Efficacy and Safety of Timolol Ophthalmic Solution as an Acute Treatment of Migraine
Condition: Migraine
MeSH terms: Migraine Disorders
Study type: Interventional
Phase: Phase 2

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.
    

Detailed 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.
    

Intervention name(s): Timolol; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Timolol is a clear solution supplied in a plastic ophthalmic dispenser.; Placebo is normal saline solution that will be supplied in container matched to Timolol container.
Other intervention name(s): 0.5% timolol ophthalmic solution; beta blocker eye drops; inactive drug
Intervention MeSH terms: Timolol; Ophthalmic Solutions
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Headache; Acute migraine headache