Comparing an oral contraceptive pill to vitamin E for treating migraines in women

Open-label Randomized Controlled Trial for the Effects of Continuous Ethinylestradiol/Levonorgestrel (30/150 μg/Day) Compared With Vitamin E (400 IU/Day) in the Treatment of Menstrually-related Migraine and Migraine During Perimenopause

This study is testing whether a birth control pill or vitamin E can help women with migraines related to their menstrual cycle or early menopause feel better.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 360 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Leiden University Medical Center (other)
• Locations: 1 site (Leiden, Zuid Holland)
• Trial ID: NCT04007874 on ClinicalTrials.gov

What this trial studies

This open-label randomized controlled trial aims to evaluate the effectiveness of continuous daily use of ethinylestradiol/levonorgestrel compared to vitamin E in women suffering from menstrually-related and perimenopausal migraines. The study will include women who experience migraines linked to their menstrual cycle or are in the early stages of menopause. Participants will be monitored for their response to treatment over a specified period, with a focus on compliance and migraine frequency. The trial seeks to address the lack of evidence-based hormonal interventions for migraine treatment in women.

Who should consider this trial

Good fit: Ideal candidates for this study are premenopausal women experiencing menstrual migraines or those in the early menopausal transition phase.

Not a fit: Patients with chronic migraines, those who smoke, or women who are pregnant or breastfeeding may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new preventive treatment option for women suffering from menstrually-related and perimenopausal migraines.

How similar studies have performed: While there is limited evidence on hormonal interventions for migraine treatment, this approach is novel and aims to fill a significant gap in current treatment options.

Eligibility criteria

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

Where this trial is running

Leiden, Zuid Holland

• Leiden University Medical Center — Leiden, Zuid Holland, Netherlands (RECRUITING)

Study contacts

• Principal investigator: Gisela M Terwindt, MD,PhD — LUMC
• Study coordinator: Britt WH van der Arend, MSc

Conditions: Migraine, Menstrual, Women, Hormones, Oral contraceptive pill, Vitamin E