A Clinical Study Examining the Safety and Effectiveness of a New Medication (Keppra®) for the Prevention of Migraine Headaches

Study Overview
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Brief Summary
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The study drug levetiracetam is FDA approved as an add-on medication in the treatment of partial onset seizures in adults with epilepsy. The trade name is Keppra®. This is an open-label trial, which means that all participating patients will receive active study drug. The Jefferson Headache Center has developed this clinical study to evaluate the safety and effectiveness of levetiracetam in preventing migraine headaches, with or without aura (visual disturbances). In addition, the study site will be performing a procedure called Transcranial Magnetic Stimulation (TMS). This procedure measures brain activity because it is thought that people with migraine experience periods of cortical hyperexcitability or over-activity in the brain. This information may help physicians in the future determine which preventive medications will work for which patients.

Official Title
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A Single-Center, Open-Label Trial Examining the Efficacy and Safety of Levetiracetam for the Prophylactic Treatment of Migraine, With or Without Aura

Conditions
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Migraine

Intervention / Treatment
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* Drug: levetiracetam
* Procedure: Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is male or female between the ages of 18 and 65 Patient has an IHS diagnosis of migraine with or without aura for at least one-year prior to screening Patient has experienced between 4 and 10 migraine headaches per month over the past six months, with at least 48 hours separating attacks Patient is able to differentiate migraine attacks from other headache types, if applicable Patient is not currently and has not in the 4 weeks preceding screening received prophylactic treatment for the indication of migraine Patients daily medications have remained at a stable dose for the 4 weeks preceding screening Patient is using or agrees to use for the duration of participation a medically acceptable form of contraception (as determined by investigator), if female of child-bearing potential Patient has negative urine pregnancy test prior to study entry, if female of child-bearing potential Patient is able to understand and comply with all study requirements Patient provides written informed consent prior to any screening procedures being conducted Exclusion Criteria: Women who are pregnant or lactating Patients with onset of migraine after 50 years of age Patients who experience > 15 headache days per month Patients who have been previously treated or are currently being treated with levitiracetam Patients who have failed greater than 3 adequate trials of other antiepileptic drugs for the prevention of migraine. Patients who, in the investigators opinion, have a history or have evidence of a medical or psychiatric condition that would expose them to an increased risk of a significant adverse event or would interfere with the assessments of efficacy and tolerability during this trial Patients with an abnormal ECG that, in the investigators opinion, would expose them to increased risk of adverse events or interfere with study drug and/or analysis of efficacy/tolerability Patients who take medication for acute treatment greater than 10 days per month over the past three months. Patients who are allergic to or have shown hypersensitivity to compounds similar to levetiracetam Patients with a history of significant drug or alcohol abuse within the past year Patients who have had a suicidal ideation in the 3 months prior to screening or has a history of attempted suicide Patients who currently have or have a history of significantly impaired renal function Patients who have participated in an investigational drug trial in the 30 days prior to the screening visit Patients who have a Beck Depression Inventory score of > 18 at screening Patients who have > 0 on question number 9 of Beck Depression Inventory (Suicidal Thoughts or Wishes question) Patients who have a defibrillator or pacemaker, an implanted medication pump, a metal plate in the skull, or metal objects inside the eye or skull (e.g. a shrapnel wound).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levatiracetam<br>Subject titrated open-label study drug to maximally tolerated dose: maximum: 3000 mg. per date. (minimum allowed daily dose to remain in study: 1000) | Drug: levetiracetam<br>* Daily dose of open label levatiracetam was 3000 mg. or maximally tolerated dose. (Maximum daily dose: 3000 mg. Minimum daily dose allowed for study participation:1000 mg)<br>* Other names: Keppra;Procedure: Transcranial Magnetic Stimulation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Outcome is Defined as Average Change in Frequency of Migraine Attacks Over Each 4-week Interval of the Treatment Period as Compared to the 4-week Baseline Period. | Number of migraine attacks will be measured at baseline (28 day period prior to start of study medication). The baseline number of attacks will be compared to that in the following 28 day intervals: visit_4 = first follow-up interval (0 to 28 days after starting study drug) visit_5 = second follow-up interval (28 to 56 days) visit_6 = third follow-up interval (56 to 84 days) visit_7 = fourth follow-up interval (84 to 126 days) The change in headache attacks post-treatment will be averaged in a multiple regression model, looking at the following: visit number, age, gender, BMI | Compare frequency of migraine attacks in baseline period to the average of the change following these 28 day periods prior to: Visit 4 (day 0-28), visit 5 (day 28-56), visit 6 (day 576-84), visit 7 (day 84-126). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Number of Migraine Days Over Each 4-week Interval of the Treatment Period as Compared to the 4-week Baseline Period | Number of migraine attacks will be measured at baseline (28 day period prior to start of study medication). The baseline number of attacks will be compared to that in the following 28 day intervals: visit_4 = first follow-up interval (0 to 28 days after starting study drug) visit_5 = second follow-up interval (28 to 56 days) visit_6 = third follow-up interval (56 to 84 days) visit_7 = fourth follow-up interval (84 to 126 days) | Baseline period (day -28 to day 0) compared to the 28 day period prior to Visit 4-7. | 
| Change in Average Severity if Migraine Attacks Per Each Consecutive 4-week Interval of the Treatment Period as Compared to the 4-week Baseline Period |  | Baseline period compared to 28 day interval prior to Visit 4-7. | 
| Change in Use of Acute Agents Attacks Per Each Consecutive 4-week Interval of the Treatment Period as Compared to the 4-week Baseline Period. |  | Baseline period compared to the 28 day period prior to each of the following visits: Visit 4-7. |