Prophylactic Treatment With Atorvastatin for Episodic Migraine.

NCT06248671 | Recruiting Phase 2 DMC

• 1 other identifier: 2022-502176-23-01
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 6

Brief Summary

The main objective of this study is to see whether the favorable preventative effect of Atorvastatin 40mg per day in episodic migraine, that was found previously in three smaller randomized controlled cross-over studies, can be confirmed in a larger, multicenter, randomized controlled parallel group study. In addition it will be investigated whether 1) there is an effect of a daily dose of 20mg Atorvastatin, 2) whether the favorable side effect profile, seen in previous studies, can be confirmed, and whether it is even better with the smaller dose, and 3) estimating the cost of Atorvastatin treatment, considering cost of medicine, cost of acute attack medicine, and cost of lost worktime.

Conditions

Episodic Migraine

Keywords

Migraine; Atorvastatin; Randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Number of migraine days

  Change in number of migraine days/4 weeks from the baseline period to the treatment period.

  4 weeks

Secondary Outcomes (4)

• Number of responders

  12 weeks

• Rate of adverse events

  12 weeks

• Number of doses with acute medication

  12 weeks

• Number of days with sick leave

  12 weeks

Study Arms (3)

Atorvastatin 40mg

ACTIVE COMPARATOR

Each participant in this arm will receive 40mg atorvastatin once daily for 84 days.

Drug: Atorvastatin 40mg

Atorvastatin 20mg

ACTIVE COMPARATOR

Each participant in this arm will receive 20mg atorvastatin once daily for 84 days.

Drug: Atorvastatin 20mg

Placebo

PLACEBO COMPARATOR

Each participant in this arm will receive placebo once daily for 84 days.

Drug: Placebo

Interventions

Atorvastatin 40mg DRUG

Each tablet will be taken once daily for 84 days.

Also known as: Lipitor

Atorvastatin 40mg

Placebo DRUG

Each tablet will be taken once daily for 84 days

Placebo

Atorvastatin 20mg DRUG

Each tablet will be taken once daily for 84 days.

Also known as: Lipitor

Atorvastatin 20mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 65 years.
• Signed informed consent.
• Episodic migraine with or without aura according to ICHD-3 criteria.
• Start of migraine before 50 years.
• No use of other migraine prophylactics during the study.
• For women of child-bearing potential, there must be no pregnancy or planned pregnancy during the study period, and use of highly effective contraception.

You may not qualify if:

• Interval headache not distinguishable from migraine.
• Chronic migraine, chronic tension-type headache, medication overuse headache or other headache occurring on ≥ 15 days/month.
• Pregnancy, planning to get pregnant, inability to use contraceptives, and lactating.
• Clinical information on or signs of cholestasis or decreased hepatic or renal function.
• High degree of comorbidity and/or frailty associated with reduced life expectancy or high likelihood of hospitalization, at the discretion of the investigator.
• Hypersensitivity to statins or previous use of statins.
• History of angioneurotic oedema.
• Use of medicines for migraine prophylaxis less than 4 weeks, or of botulinum toxin less than 16 weeks, prior to start of study.
• Current use of antiviral treatment against hepatitis C.
• Significant psychiatric illness.
• Having tried ≥ 3 prophylactic drugs against migraine during the last 10 years.
• Requiring detoxification from acute medication (triptans, opioids).
• Consistently failing to respond to any acute migraine medication.
• Alcohol or illicit drug dependence.
• Inability to understand study procedures and to comply with them for the entire length of the study.

Sponsors & Collaborators

• St. Olavs Hospital: lead
• Haukeland University Hospital: collaborator
• University Hospital of North Norway: collaborator
• University Hospital, Akershus: collaborator
• Ullevaal University Hospital: collaborator

Study Sites (6)

Haukeland University Hospital

Bergen, Norway

RECRUITING

University Hospital, Akershus

Lørenskog, Norway

NOT YET RECRUITING

Oslo University Hospital, Rikshospitalet

Oslo, Norway

NOT YET RECRUITING

Oslo University Hospital, Ullevål

Oslo, Norway

NOT YET RECRUITING

University Hospital Northern Norway

Tromsø, Norway

RECRUITING

St. Olavs hospital

Trondheim, 7022, Norway

RECRUITING

Related Publications (32)

• Steiner TJ, Stovner LJ, Jensen R, Uluduz D, Katsarava Z; Lifting The Burden: the Global Campaign against Headache. Migraine remains second among the world's causes of disability, and first among young women: findings from GBD2019. J Headache Pain. 2020 Dec 2;21(1):137. doi: 10.1186/s10194-020-01208-0. No abstract available.

  PMID: 33267788 BACKGROUND

• Stovner LJ, Hagen K, Linde M, Steiner TJ. The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. J Headache Pain. 2022 Apr 12;23(1):34. doi: 10.1186/s10194-022-01402-2.

  PMID: 35410119 BACKGROUND

• Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, Sandor 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.

  PMID: 19708964 BACKGROUND

• Langohr HD, Gerber WD, Koletzki E, Mayer K, Schroth G. Clomipramine and metoprolol in migraine prophylaxis--a double-blind crossover study. Headache. 1985 Mar;25(2):107-13. doi: 10.1111/j.1526-4610.1985.hed2502107.x. No abstract available.

  PMID: 3886599 BACKGROUND

• Ziegler DK, Hurwitz A, Hassanein RS, Kodanaz HA, Preskorn SH, Mason J. Migraine prophylaxis. A comparison of propranolol and amitriptyline. Arch Neurol. 1987 May;44(5):486-9. doi: 10.1001/archneur.1987.00520170016015.

  PMID: 3579659 BACKGROUND

• Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003 Jan 1;289(1):65-9. doi: 10.1001/jama.289.1.65.

  PMID: 12503978 BACKGROUND

• Stovner LJ, Linde M, Gravdahl GB, Tronvik E, Aamodt AH, Sand T, Hagen K. A comparative study of candesartan versus propranolol for migraine prophylaxis: A randomised, triple-blind, placebo-controlled, double cross-over study. Cephalalgia. 2014 Jun;34(7):523-32. doi: 10.1177/0333102413515348. Epub 2013 Dec 11.

  PMID: 24335848 BACKGROUND

• Mei D, Capuano A, Vollono C, Evangelista M, Ferraro D, Tonali P, Di Trapani G. Topiramate in migraine prophylaxis: a randomised double-blind versus placebo study. Neurol Sci. 2004 Dec;25(5):245-50. doi: 10.1007/s10072-004-0350-0.

  PMID: 15624081 BACKGROUND

• Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, Neto W, Schwabe S, Jacobs D; MIGR-002 Study Group. Topiramate for migraine prevention: a randomized controlled trial. JAMA. 2004 Feb 25;291(8):965-73. doi: 10.1001/jama.291.8.965.

  PMID: 14982912 BACKGROUND

• Bulut S, Berilgen MS, Baran A, Tekatas A, Atmaca M, Mungen B. Venlafaxine versus amitriptyline in the prophylactic treatment of migraine: randomized, double-blind, crossover study. Clin Neurol Neurosurg. 2004 Dec;107(1):44-8. doi: 10.1016/j.clineuro.2004.03.004.

  PMID: 15567552 BACKGROUND

• Couch JR; Amitriptyline Versus Placebo Study Group. Amitriptyline in the prophylactic treatment of migraine and chronic daily headache. Headache. 2011 Jan;51(1):33-51. doi: 10.1111/j.1526-4610.2010.01800.x. Epub 2010 Nov 10.

  PMID: 21070231 BACKGROUND

• Sacco S, Bendtsen L, Ashina M, Reuter U, Terwindt G, Mitsikostas DD, Martelletti P. Correction to: European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. J Headache Pain. 2019 May 23;20(1):58. doi: 10.1186/s10194-019-0972-5.

  PMID: 31122188 BACKGROUND

• Katsarava Z, Mania M, Lampl C, Herberhold J, Steiner TJ. Poor medical care for people with migraine in Europe - evidence from the Eurolight study. J Headache Pain. 2018 Feb 1;19(1):10. doi: 10.1186/s10194-018-0839-1.

  PMID: 29392600 BACKGROUND

• Buettner C, Nir RR, Bertisch SM, Bernstein C, Schain A, Mittleman MA, Burstein R. Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial. Ann Neurol. 2015 Dec;78(6):970-81. doi: 10.1002/ana.24534. Epub 2015 Nov 13.

  PMID: 26418341 BACKGROUND

• Hesami O, Sistanizad M, Asadollahzade E, Johari MS, Beladi-Moghadam N, Mazhabdar-Ghashghai H. Comparing the Effects of Atorvastatin With Sodium Valproate (Divalproex) on Frequency and Intensity of Frequent Migraine Headaches: A Double-blind Randomized Controlled Study. Clin Neuropharmacol. 2018 May/Jun;41(3):94-97. doi: 10.1097/WNF.0000000000000280.

  PMID: 29746282 BACKGROUND

• Ganji R, Majdinasab N, Hesam S, Rostami N, Sayyah M, Sahebnasagh A. Does atorvastatin have augmentative effects with sodium valproate in prevention of migraine with aura attacks? A triple-blind controlled clinical trial. J Pharm Health Care Sci. 2021 Apr 1;7(1):12. doi: 10.1186/s40780-021-00198-8.

  PMID: 33789774 BACKGROUND

• Sherafat A, Sahebnasagh A, Rahmany R, Mohammadi F, Saghafi F. The preventive effect of the combination of atorvastatin and nortriptyline in migraine-type headache: a randomized, triple-blind, placebo-controlled trial. Neurol Res. 2022 Apr;44(4):311-317. doi: 10.1080/01616412.2021.1981105. Epub 2022 Jan 17.

  PMID: 35037597 BACKGROUND

• Endo A. The discovery and development of HMG-CoA reductase inhibitors. J Lipid Res. 1992 Nov;33(11):1569-82. No abstract available.

  PMID: 1464741 BACKGROUND

• Musial J, Undas A, Gajewski P, Jankowski M, Sydor W, Szczeklik A. Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia. Int J Cardiol. 2001 Feb;77(2-3):247-53. doi: 10.1016/s0167-5273(00)00439-3.

  PMID: 11182189 BACKGROUND

• Yanuck D, Mihos CG, Santana O. Mechanisms and clinical evidence of the pleiotropic effects of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in central nervous system disorders: a comprehensive review. Int J Neurosci. 2012 Nov;122(11):619-29. doi: 10.3109/00207454.2012.704455. Epub 2012 Aug 14.

  PMID: 22720798 BACKGROUND

• Zhou Q, Liao JK. Pleiotropic effects of statins. - Basic research and clinical perspectives -. Circ J. 2010 May;74(5):818-26. doi: 10.1253/circj.cj-10-0110. Epub 2010 Apr 15.

  PMID: 20424337 BACKGROUND

• Salagre E, Fernandes BS, Dodd S, Brownstein DJ, Berk M. Statins for the treatment of depression: A meta-analysis of randomized, double-blind, placebo-controlled trials. J Affect Disord. 2016 Aug;200:235-42. doi: 10.1016/j.jad.2016.04.047. Epub 2016 Apr 27.

  PMID: 27148902 BACKGROUND

• Millar PJ, Floras JS. Statins and the autonomic nervous system. Clin Sci (Lond). 2014 Mar;126(6):401-15. doi: 10.1042/CS20130332.

  PMID: 24274967 BACKGROUND

• Lennernas H. Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet. 2003;42(13):1141-60. doi: 10.2165/00003088-200342130-00005.

  PMID: 14531725 BACKGROUND

• Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW; STELLAR Study Group. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003 Jul 15;92(2):152-60. doi: 10.1016/s0002-9149(03)00530-7.

  PMID: 12860216 BACKGROUND

• Diener HC, Tassorelli C, Dodick DW, Silberstein SD, Lipton RB, Ashina M, Becker WJ, Ferrari MD, Goadsby PJ, Pozo-Rosich P, Wang SJ, Houle TT, Hoek TCVD, Martinelli D, Terwindt GM; International Headache Society Clinical Trials Committee. Guidelines of the International Headache Society for controlled trials of preventive treatment of migraine attacks in episodic migraine in adults. Cephalalgia. 2020 Sep;40(10):1026-1044. doi: 10.1177/0333102420941839. Epub 2020 Jul 28.

  PMID: 32722936 BACKGROUND

• Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.

  PMID: 29368949 BACKGROUND

• Bhatt A. Protocol deviation and violation. Perspect Clin Res. 2012 Jul;3(3):117. doi: 10.4103/2229-3485.100663. No abstract available.

  PMID: 23125964 BACKGROUND

• Buettner C, Burstein R. Association of statin use and risk for severe headache or migraine by serum vitamin D status: a cross-sectional population-based study. Cephalalgia. 2015 Aug;35(9):757-66. doi: 10.1177/0333102414559733. Epub 2014 Nov 25.

  PMID: 25424706 BACKGROUND

• Finegold JA, Manisty CH, Goldacre B, Barron AJ, Francis DP. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. Eur J Prev Cardiol. 2014 Apr;21(4):464-74. doi: 10.1177/2047487314525531. Epub 2014 Mar 12.

  PMID: 24623264 BACKGROUND

• Gupta A, Thompson D, Whitehouse A, Collier T, Dahlof B, Poulter N, Collins R, Sever P; ASCOT Investigators. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. 2017 Jun 24;389(10088):2473-2481. doi: 10.1016/S0140-6736(17)31075-9. Epub 2017 May 2.

  PMID: 28476288 BACKGROUND

• Jenssen AB, Stovner LJ, Tronvik E, Sand T, Helde G, Gravdahl GB, Hagen K. The crossover design for migraine preventives: an analyses of four randomized placebo-controlled trials. J Headache Pain. 2019 Dec 27;20(1):119. doi: 10.1186/s10194-019-1067-z.

  PMID: 31881823 BACKGROUND

Related Links

• Statins rarely cause adverse effects
• Treatment with statins
• Serendipity atorvastatin and vitamin D

MeSH Terms

Conditions

Migraine Disorders

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Marte-Helene Bjørk, Professor

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

• Kjersti G Vetvik, Ph.d.

  University Hospital, Akershus

  PRINCIPAL INVESTIGATOR

• Bendik S Winsvold, Post.doc.

  Oslo University Hospital, Ullevål

  PRINCIPAL INVESTIGATOR

• Anne H Aamodt, Senior researcher

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

• Lise R Øie, Post.doc.

  St. Olavs Hospital

  PRINCIPAL INVESTIGATOR

• Linn H Steffensen, Associate Professor II

  University Hospital Northern Norway

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lise R Øie, Post.doc.

CONTACT

0047 41419596; lise.r.oie@ntnu.no

Joakim H Østhus, Cand.med.

CONTACT

0047 93837036; Joakim.h.osthus@ntnu.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Triple blind (blinded to patients, study personnel, and statistician).
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel group study with three arms, comparing Atorvastatin 20 mg and 40 mg against placebo. Each participant will receive 84 encapsulated tablets. The participant will take one capsule orally each day, preferably at the same time of the day.

Study Record Dates

• First Submitted: January 19, 2024
• First Posted: February 8, 2024
• Study Start: May 1, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): February 28, 2029
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

NO (6)