Can DFN-15 Terminate Migraine With Allodynia?

Study Overview
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Brief Summary
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The majority of migraineurs seeking secondary or tertiary medical care develop cutaneous allodynia during the course of migraine, a sensory abnormality mediated by sensitization of central trigeminovascular neurons in the spinal trigeminal nucleus. Triptan therapy can render allodynic migraineurs pain-free within a narrow window of time (20-120 min) that opens with the onset of pain and closes with the establishment of central sensitization. This calls for the development of drugs that can tackle ongoing central sensitization and render allodynic migraineurs pain-free after the window for triptan therapy has expired. There are two main objectives the investigators seek to achieve from this study: to determine whether oral administration of DFN-15 (solution of a COX2 inhibitor, Celecoxib) terminates migraine attacks when given to allodynic participants 3 hours after attack onset; and to determine whether mechanical and heat allodynia that develop during acute migraine attacks could be reversed by late (> 3hrs after attack onset) treatment with DFN-15. Participants will be recruited from the Headache Center and randomized in a double-blinded fashion to receive either the active drug (DFN-15) or placebo in a ratio of 4:1.The participants will be instructed to return to the clinic during a migraine. At the 'during-migraine' visit, which will begin 3 hours after onset of headache, the investigators will document headache intensity, associated symptoms, and mechanical and heat pain threshold (first) before treatment (at 180 min after onset of headache) and (second) at a 120 min after treatment (5 hours after headache onset). Based on our prior experience studying migraine patients, the investigators plan to screen 100 patients to achieve 50 participants completing the 2 study visits as planned. The active drug group will consist of 80/100 patients and 20/100 patients will receive the placebo. The study will be terminated as soon as the first 40 participants who received the DFN-15 and first 10 patients who received placebo completed visit 2.

Official Title
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Effects of DFN-15 on Migraine With Allodynia

Conditions
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Migraine With Aura, Migraine Without Aura, Allodynia

Intervention / Treatment
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* Drug: DFN-15
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of migraine with or without aura for at least 3 years, based on the International Classification of Headache disorders Two or more migraine attacks per month on average during the year prior to enrollment Ability to give written consent to enrollment Exclusion Criteria: Fifteen or more headache days per month, on average Aspirin or NSAID induced asthma or allergy Sulfa allergy Any woman who is pregnant or lactacting History of any of the following: Coronary artery bypass surgery, heart attack, angina, stroke, serious gastrointestinal bleeding, peptic ulcer disease, and/or chronic kidney disease Medical Conditions requiring the use of diuretics or daily anticoagulants Severe uncontrolled medical problems or medications that may influence measurements

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment Group<br>DFN-15 | Drug: DFN-15<br>* Oral Solution of 4.8 mL containing 120 mg of DFN-15<br>* Other names: Celecoxib;|
| Placebo Comparator: Placebo Group<br> | Other: Placebo<br>* Oral Solution of 4.8 mL containing 0 mg of DFN-15<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache Pain Intensity | The proportion of patients demonstrating a decrease in their headache pain intensity is greater than 50% (post-treatment compared to pre-treatment). Pain intensity will be measured with a visual analog scale from 0 (no pain) to 10 (worst pain imaginable). | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Allodynia | The proportion of patients demonstrating allodynia before and after treatment; allodynia to thermal stimuli is defined as pain threshold < 41 degrees Celsius, and to mechanical stimuli as pressure pain threshold of < 30 g. | Up to 6 months |