Oral Contraceptive Pill Compared With Vitamin E in Women With Migraine

NCT ID: NCT04007874

Last Updated: 2023-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

360 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-10

Study Completion Date

2024-12-31

Brief Summary

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Open-label randomized controlled trial to study the efficacy of continuous daily use of ethinylestradiol/levonorgestrel (30/150 µg/day) compared with vitamin E (400 IU/day) in the treatment of women with menstrually-related and perimenopausal migraine.

Detailed Description

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Rationale: The prevalence of migraine is three times higher in women than in men. Clinical and epidemiological studies suggest a prominent role for sex hormones in female migraine patients. Menstruation is an important factor increasing the susceptibility for an upcoming attack. Perimenstrual migraine attacks are also more disabling, longer lasting, and more difficult to treat than other attacks. Hormonal fluctuations during menopausal transition are associated with increased susceptibility for migraine as well, whereas hormonal changes in migraine during pregnancy seem to be associated with decreased attack frequency. Thus, sex hormonal conditions seem to affect the susceptibility for migraine attacks in women, but there is a lack of understanding the underlying pathophysiological mechanism. Currently, there is no clear evidence-based hormonal intervention for the treatment of migraine in women. The investigators hypothesize that continuous daily use of an oral contraceptive pill will be an effective, well-tolerated preventive treatment for 1) menstrually-related migraine and 2) perimenopausal migraine.

Objective: To study the efficacy of continuous daily use of ethinylestradiol/levonorgestrel (30/150 µg/day) compared with vitamin E (400 IU/day) in the treatment of menstrually-related and perimenopausal migraine.

Study design: Open-label randomized controlled trial. Study population: Women with menstrually-related or pure menstrual migraine and women with perimenopausal migraine.

Intervention: Continuous daily use of ethinylestradiol/levonorgestrel (30/150 µg/day) compared with vitamin E (400 IU/day).

Primary endpoint: Change in monthly migraine days from baseline to the last 4 weeks of treatment (weeks 9-12).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The study will encompass a period of 4 months (1 baseline month and 3 treatment months). Patients have to fill out daily headache diaries throughout the study using a web-based app (≈ 5 min). Patients visit the headache clinic thrice, once for inclusion, once during the baseline period and once after 3 months of therapy (duration ≈ 1 hour). During the first and last visit blood samples will be taken. Patients will be contacted twice during follow-up to evaluate (S)AE's. Treatment with the oral contraceptive pill is accompanied by a very low risk of developing thromboembolisms. Participation might benefit participants by reducing their migraine attack frequency or intensity.

Conditions

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Migraine Migraine;Menstrual

Keywords

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Migraine Women Hormones Oral contraceptive pill Vitamin E

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Open-label randomized controlled trial
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Ethinylestradiol/levonorgestrel

Ethinylestradiol/levonorgestrel 30/150 µg oral tablets once daily without a stopweek for 3 months

Group Type EXPERIMENTAL

Ethinylestradiol/levonorgestrel

Intervention Type DRUG

Ethinylestradiol/levonorgestrel 30/150 µg oral tablets once daily without a stopweek for 3 months

Vitamin E

Vitamin E 400 IU oral capsules once daily for 3 months

Group Type ACTIVE_COMPARATOR

Vitamin E

Intervention Type DRUG

Vitamin E 400 IU oral capsules once daily for 3 months

Interventions

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Ethinylestradiol/levonorgestrel

Ethinylestradiol/levonorgestrel 30/150 µg oral tablets once daily without a stopweek for 3 months

Intervention Type DRUG

Vitamin E

Vitamin E 400 IU oral capsules once daily for 3 months

Intervention Type DRUG

Other Intervention Names

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Microgynon 30 RVG 08204

Eligibility Criteria

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Inclusion Criteria

* Female
* Premenopausal with menstrual migraine OR migraine during the early menopausal transition phase (a difference of 7 days or more in length of consecutive cycles, which should occur at least twice in a period of 12 menstrual cycles)
* Demonstrated at least 80% compliance with eDiary during baseline period
* No or stable for at least two months on prophylactic medication

Exclusion Criteria

* Smoking
* Migraine with aura
* Chronic migraine with 15 or more headache days per month/with 8 or more migraine days per month
* Medication-overuse headache (ICHD-3 criteria)
* Women who are breastfeeding, pregnant, or planning to become pregnant
* Oral contraceptive use and not willing to undergo washout period (stop for two consecutive months)
* Vitamin E use at start of the study
* Use of other sex hormone containing treatments
* Increased risk of VTE: history of VTE or thrombophlebitis, hereditary predisposition for VTE (APC resistance, protein C or S deficiency, antithrombin deficiency), VTE in first-degree family member at young age, long term immobilisation
* Increased risk of ATE: history of ATE, hereditary predisposition for ATE (hyperhomocysteinemia, antiphospholipid antibodies), ATE in first-degree family member at young age, diabetes mellitus, total cholesterol ≥ 6.5
* Other contraindication for oral contraceptives: liver malignancy, schistosomiasis, HIV/aids, use of immunosuppressives, tuberculosis, sex-hormone-dependent malignancies (breast, endometrial or ovary carcinomas), pancreatitis, vaginal bleeding with unknown cause, other diseases that can influence vessels (malignancies, heart valve disorders, atrial fibrillation, SLE, haemolytic uremic syndrome, chronic inflammatory bowel disease, sickle cell disease)
* Contraindication for vitamin E: vitamin K deficiency
* Hypersensitivity for any of the compounds in oral contraceptive or vitamin E
* Spontaneous postmenopausal status (menstrual bleedings have ceased for 12 consecutive months)
* Iatrogenic postmenopausal status
* Inability to complete the electronic diary in an accurate manner
* Any serious illness that can compromise study participation
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Erasmus Medical Center

OTHER

Sponsor Role collaborator

Netherlands Brain Foundation

OTHER

Sponsor Role collaborator

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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G.M. Terwindt, MD

Head of headache clinic, Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gisela M Terwindt, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

LUMC

Locations

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Leiden University Medical Center

Leiden, South Holland, Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Britt WH van der Arend, MSc

Role: CONTACT

Phone: +31715266065

Email: [email protected]

Facility Contacts

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Britt WH van der Arend, MD

Role: primary

References

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van der Arend BWH, van Casteren DS, Verhagen IE, MaassenVanDenBrink A, Terwindt GM. Continuous combined oral contraceptive use versus vitamin E in the treatment of menstrual migraine: rationale and protocol of a randomized controlled trial (WHAT!). Trials. 2024 Feb 15;25(1):123. doi: 10.1186/s13063-024-07955-8.

Reference Type DERIVED
PMID: 38360739 (View on PubMed)

Other Identifiers

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2018-004096-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WHATT

Identifier Type: -

Identifier Source: org_study_id