Flunarizine Versus Topiramate for Chronic Migraine Prophylaxis

Chronic Migraine Clinical Trial

Official title:

Flunarizine Versus Topiramate for Chronic Migraine Prophylaxis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02639598
• Other study ID #: 2012-04-046B
• Status: Completed
• Phase: Phase 4
• First received: December 16, 2015
• Last updated: December 20, 2015
• Start date: June 2012
• Est. completion date: March 2015

Study information

• Verified date: December 2015
• Source: Taipei Veterans General Hospital, Taiwan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: March 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Migraine
• Migraine Disorders

Intervention

Drug:
• Flunarizine
as in "arm descriptions"
• Topiramate
as in "arm descriptions"

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Taipei Veterans General Hospital, Taiwan

References & Publications (12)

Bartolini M, Silvestrini M, Taffi R, Lanciotti C, Luconi R, Capecci M, Provinciali L. Efficacy of topiramate and valproate in chronic migraine. Clin Neuropharmacol. 2005 Nov-Dec;28(6):277-9. — View Citation

Diener HC, Bussone G, Van Oene JC, Lahaye M, Schwalen S, Goadsby PJ; TOPMAT-MIG-201(TOP-CHROME) Study Group. Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia. 2007 Jul;27(7):814-23. Ep — View Citation

Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, Sándor PS; European Federation of Neurological Societies. EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force. Eur J Neurol. 2009 Sep;16(9):968-81. doi: 10.1111/j.1468-1331.2009.02748.x. — View Citation

Lewis D, Ashwal S, Hershey A, Hirtz D, Yonker M, Silberstein S; American Academy of Neurology Quality Standards Subcommittee; Practice Committee of the Child Neurology Society. Practice parameter: pharmacological treatment of migraine headache in children and adolescents: report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society. Neurology. 2004 Dec 28;63(12):2215-24. Review. — View Citation

Li HL, Kwan P, Leung H, Yu E, Tsoi TH, Hui AC, Sheng B, Lau KK. Topiramate for migraine prophylaxis among Chinese population. Headache. 2007 Apr;47(4):616-9. — View Citation

Martínez-Lage JM. Flunarizine (Sibelium) in the prophylaxis of migraine. An open, long-term, multicenter trial. Cephalalgia. 1988;8 Suppl 8:15-20. — View Citation

Pringsheim T, Davenport W, Mackie G, Worthington I, Aubé M, Christie SN, Gladstone J, Becker WJ; Canadian Headache Society Prophylactic Guidelines Development Group. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci. 2012 Mar;39(2 Suppl 2):S1-59. — View Citation

Silberstein S, Lipton R, Dodick D, Freitag F, Mathew N, Brandes J, Bigal M, Ascher S, Morein J, Wright P, Greenberg S, Hulihan J. Topiramate treatment of chronic migraine: a randomized, placebo-controlled trial of quality of life and other efficacy measur — View Citation

Silberstein SD, Lipton RB, Dodick DW, Freitag FG, Ramadan N, Mathew N, Brandes JL, Bigal M, Saper J, Ascher S, Jordan DM, Greenberg SJ, Hulihan J; Topiramate Chronic Migraine Study Group. Efficacy and safety of topiramate for the treatment of chronic migr — View Citation

Silvestrini M, Bartolini M, Coccia M, Baruffaldi R, Taffi R, Provinciali L. Topiramate in the treatment of chronic migraine. Cephalalgia. 2003 Oct;23(8):820-4. — View Citation

Treatment Guideline Subcommittee of the Taiwan Headache Society. [Treatment guidelines for preventive treatment of migraine]. Acta Neurol Taiwan. 2008 Jun;17(2):132-48. Review. Chinese. — View Citation

Visudtibhan A, Lusawat A, Chiemchanya S, Visudhiphan P. Flunarizine for prophylactic treatment of childhood migraine. J Med Assoc Thai. 2004 Dec;87(12):1466-70. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	reduction of total number of headache days (by diary log)	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.	week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)
Primary	reduction of number of migraine days (by diary log)	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.	week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)
Secondary	reduction of number of days of acute abortive medication intake (by diary log)	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.	week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)
Secondary	reduction of number of acute abortive medication tablets taken (by diary log)	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.	week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)
Secondary	fifty percent responder rate (by diary log)	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.	week 7 to 8 after treatment (T4) compared to week -2 to 0 before treatment (T0)