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

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

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.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: levetiracetam; Procedure: Transcranial Magnetic Stimulation

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson Headache Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levatiracetam; 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; 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); Other Names: Keppra; Procedure: Transcranial Magnetic Stimulation

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: UCB Pharma
• Investigators: Principal Investigator: William B Young, MD, Thomas Jefferson University, Jefferson Headache Center

Study record dates

Study Major Dates

• Study Start: September 1, 2002
• Primary Completion (Actual): January 1, 2005
• Study Completion (Actual): September 1, 2005

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 20, 2005

Study Record Updates

• Last Update Posted (Estimate): August 11, 2011
• Last Update Submitted That Met QC Criteria: July 15, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: WBY/LEV01; 080-19000-H80001