MigrainePhase 2NCT03836664
A Randomized Study Evaluating the Efficacy and Safety of Timolol Ophthalmic Solution as an Acute Treatment of Migraine
A Phase 2 study testing Timolol in people with Migraine, run by University of Kansas Medical Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Migraine
- What is being tested?
- Timolol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Feb 2017to 14 Apr 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of migraine, with or without aura, according to ICHD-2 criteria (Appendix A) for at least 1 year prior to screening; experience an average of 1 to 8 migraines per month.
- Females must be practicing an effective method of birth control before entry and throughout the study, or be surgically sterile, or be postmenopausal
- Females of child-bearing potential must have a negative urine pregnancy test
- Subjects should be able to demonstrate the ability to properly administer study medication
- Subjects should be able and willing to read and comprehend written instructions and complete the diary information required by the protocol
- Subjects must be capable, in the opinion of the Investigator, of providing informed consent or assent to participate in the study
- Subjects (and their legally acceptable representatives, if applicable) must provide an informed consent indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study
Who cannot join
- Inability to distinguish other headaches from migraine
- Experiences headache of any kind at a frequency greater than or equal to 15 days per month
- Current use of medication for migraine prophylaxis that has not been stable (no dose adjustment) for 30 days prior to screening
- Chronic opioid therapy for headaches (> 3 consecutive days in the 30 days prior to screening)
- Hemiplegic migraine
- History, symptoms or signs of ischemic cardiac, cerebrovascular or peripheral vascular syndromes
Show all 21Show fewer
- History of glaucoma and/or current treatment with prescription eye drops
- History of naso-lacrimal duct ("tear duct problem" to patients) obstruction or surgery for such
- Active treatment by ophthalmologist or optometrist for any severe ophthalmic disease or problem
- Any physical problems or co-ordination difficulty or eye avoidance sensitivity ("squeezer") that would preclude proper installation of eye drops in either or both eyes
- History of uncontrolled asthma, COPD, or reversible airway disease which in the opinion of the investigator would be worsened by the use of beta blockers
- History of clinically symptomatic bradycardia, congestive heart failure, or hypotension
- Uncontrolled Diabetes Mellitus
- Uncontrolled Hyperthyroidism
- History (within 2 years) of drug or alcohol abuse
- Systemic disease, which in the opinion of the Investigator, would contraindicate participation
- History of a neurological or psychiatric condition, which in the opinion of the Investigator would contraindicate participation
- History of hypersensitivity or intolerance to beta-blockers eye drops
- Pregnant or lactating women
- Have taken any investigational medication within 12 weeks before randomization, or are scheduled to receive an investigational drug
- Subjects, who in opinion of the Investigator, should not be enrolled in the study because of the precautions, warnings or contra-indications sections of the timolol Package Insert
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kansas Medical Center
Kansas City, Kansas, 66160
About this study
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
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.
Read the 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.
- Conditions
- Migraine
- Being tested
- Timolol, Placebo
- Keywords
- Headache, Acute migraine headache
- Medical subject headings
- Migraine Disorders, Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TimololDrug
Also called 0.5% timolol ophthalmic solution, beta blocker eye drops
Timolol is a clear solution supplied in a plastic ophthalmic dispenser.
PlaceboDrug
Also called inactive drug
Placebo is normal saline solution that will be supplied in container matched to Timolol container.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Timolol | Experimental | 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. Receives: Drug: Timolol |
| Group 2: Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Headache Severity
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.
Measured: Headache/ pain severity at onset and at 120 minutes post intervention use
Secondary outcomes (2)
Adverse Reaction From Using Timolol Eye Drops
Measured by number of adverse events experienced by the participants from the intervention. Each adverse event was counted as one.
Measured: 8 weeks
Number of Participants Satisfied With Intervention
Measured by patient-reported satisfaction questionnaire. Satisfaction level was looked at as "satisfactory and very satisfactory" compared to "neutral and unsatisfied".
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2019
- Study start27 Feb 2017
- Primary completion14 Apr 2018
- Study completion14 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MigraineStudies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dipika Aggarwal, MD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03836664
- Sponsor's protocol ID
- STUDY00140465
- Status last verified
- Jul 2019
- First submitted
- 8 Feb 2019
- Last updated
- 2 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03836664
- Acronym / sponsor ID
- STUDY00140465
- Conditions
- Migraine
- Keywords
- Headache, Acute migraine headache
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Study start
- 27 Feb 2017 (actual)
- Primary completion
- 14 Apr 2018 (actual)
- Study completion
- 14 Apr 2018 (actual)
- First posted
- 11 Feb 2019 (actual)
- Results
- Posted 2 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: Timolol | Experimental | Drug: TimololParticipants 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. |
| Group 2: Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosis of migraine, with or without aura, according to ICHD-2 criteria (Appendix A) for at least 1 year prior to screening; experience an average of 1 to 8 migraines per month.
- Females must be practicing an effective method of birth control before entry and throughout the study, or be surgically sterile, or be postmenopausal
- Females of child-bearing potential must have a negative urine pregnancy test
- Subjects should be able to demonstrate the ability to properly administer study medication
- Subjects should be able and willing to read and comprehend written instructions and complete the diary information required by the protocol
Key exclusion criteria (21 listed)
- Inability to distinguish other headaches from migraine
- Experiences headache of any kind at a frequency greater than or equal to 15 days per month
- Current use of medication for migraine prophylaxis that has not been stable (no dose adjustment) for 30 days prior to screening
- Chronic opioid therapy for headaches (> 3 consecutive days in the 30 days prior to screening)
- Hemiplegic migraine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TimololAlso: 0.5% timolol ophthalmic solution, beta blocker eye dropsTimolol is a clear solution supplied in a plastic ophthalmic dispenser. | Drug | Group 1: Timolol |
| PlaceboAlso: inactive drugPlacebo is normal saline solution that will be supplied in container matched to Timolol container. | Drug | Group 2: Placebo |
Primary outcome
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.
2 secondary outcomes
Adverse Reaction From Using Timolol Eye Drops
Time frame: 8 weeks
Number of Participants Satisfied With Intervention
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dipika Aggarwal, MD principal investigator
University of Kansas Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Timolol in people with Migraine, run by University of Kansas Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Headache Severity (time frame: Headache/ pain severity at onset and at 120 minutes post intervention use). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2019.