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Flunarizine Versus Topiramate for Chronic Migraine Prophylaxis

Phase 4
Completed
Conditions
Chronic Migraine
Interventions
Registration Number
NCT02639598
Lead Sponsor
Taipei Veterans General Hospital, Taiwan
Brief Summary

Chronic migraine (CM) is a prevalent and devastating disorder with limited therapeutic options. This study explored the efficacy of 10 mg/day flunarizine for CM prophylaxis as compared with 50 mg/day topiramate.

Detailed Description

Chronic migraine (CM) is a prevalent and devastating disorder with limited therapeutic options. This study explored the efficacy of 10 mg/day flunarizine for CM prophylaxis as compared with 50 mg/day topiramate.

We conducted a prospective, randomized, open-label, blinded-endpoint (PROBE) trial. Patients with CM were randomized (1:1) to flunarizine and topiramate treatment groups.

This study consisted of two periods: a prospective baseline screening period lasting up to 2 weeks (week -2 to week 0, T0), and a treatment period lasting 8 weeks after enrollment (weeks 0-8, T1-T4).

The treatment phase consisted of a 2-week titration period (T1) and a 6-week maintenance period (T2-T4). During the titration period, subjects were given 25 mg/day topiramate or 5 mg/day flunarizine once daily in the first week, followed by 50 mg/day topiramate or 10 mg/day flunarizine in divided doses (twice daily) in the second week. When subjects could not tolerate this target dose, the initial dose was continued through T4.

Patients were followed per 2 weeks at the Headache Clinic. At each visit, diaries were collected and directed to the outcome evaluators, who were blinded to the patients' treatment.

The primary outcomes assessed were the reductions in the total numbers of headache days and migraine days after 8 weeks of treatment (weeks 7 to 8 vs. weeks -2 to 0). Secondary outcomes were reductions in the numbers of days of acute abortive medication intake and acute abortive medication tablets taken, and the 50% responder rate.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
62
Inclusion Criteria
  • ICHD-IIR criteria for CM (as reported by the patient)
  • Experienced ≥7 days of headache lasting ≥30 min during T0 (-2 week to 0 week).
  • On ≥4 of these days, subjects were required to have experienced migrainous headache
  • Prophylaxis-naïve (i.e., patients could not receive any preventive medications)
  • With and without medication overuse
Exclusion Criteria
  • Headache type other than CM
  • Migraine onset after the age of 50 years
  • CM onset after the age of 60 years
  • Previous history of migraine prophylaxis before enrollment
  • Pregnancy or nursing status
  • History of hepatic or renal disorder, nephrolithiasis or other severe systemic disease
  • Severe depression (BDI score ≥ 30 at visit 1)
  • Conditions incompatible with MRI, such as claustrophobia or metallic or electric implants

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
flunarizineFlunarizineThis study consisted of two periods: a prospective baseline screening period lasting up to 2 weeks (week -2 to week 0, T0), and a treatment period lasting 8 weeks after enrollment (weeks 0-8, T1-T4). The treatment phase consisted of a 2-week titration period (T1) and a 6-week maintenance period (T2-T4). During the titration period, subjects were given 5 mg/day flunarizine once daily in the first week, followed by 10 mg/day flunarizine in divided doses (twice daily) in the second week. When subjects could not tolerate this target dose, the initial dose was continued through T4.
topiramateTopiramateThis study consisted of two periods: a prospective baseline screening period lasting up to 2 weeks (week -2 to week 0, T0), and a treatment period lasting 8 weeks after enrollment (weeks 0-8, T1-T4). The treatment phase consisted of a 2-week titration period (T1) and a 6-week maintenance period (T2-T4). During the titration period, subjects were given 25 mg/day topiramate once daily in the first week, followed by 50 mg/day topiramate in divided doses (twice daily) in the second week. When subjects could not tolerate this target dose, the initial dose was continued through T4.
Primary Outcome Measures
NameTimeMethod
reduction of total number of headache days (by diary log)week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)

Patients were followed per 2 weeks at the Headache Clinic. At each visit, diaries were collected, and information within the diary was used for outcome measurement.

reduction of number of migraine days (by diary log)week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)

Patients were followed per 2 weeks at the Headache Clinic. At each visit, diaries were collected, and information within the diary was used for outcome measurement.

Secondary Outcome Measures
NameTimeMethod
fifty percent responder rate (by diary log)week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)

Patients were followed per 2 weeks at the Headache Clinic. At each visit, diaries were collected, and information within the diary was used for outcome measurement.

reduction of number of days of acute abortive medication intake (by diary log)week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)

Patients were followed per 2 weeks at the Headache Clinic. At each visit, diaries were collected, and information within the diary was used for outcome measurement.

reduction of number of acute abortive medication tablets taken (by diary log)week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)

Patients were followed per 2 weeks at the Headache Clinic. At each visit, diaries were collected, and information within the diary was used for outcome measurement.

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