Oral Contraceptive Pill Compared With Vitamin E in Women With Migraine

NCT04007874 | Unknown Phase 3 DMC

• 2 other identifiers: WHATT2018-004096-12
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Migraine; Migraine;Menstrual

Keywords

Migraine; Women; Hormones; Oral contraceptive pill; Vitamin E

Outcome Measures

Primary Outcomes (1)

• Number of migraine days

  Change in monthly migraine days

  From baseline to the last 4 weeks of treatment (weeks 9-12)

Secondary Outcomes (5)

• Number of headache days

  From baseline to the last 4 weeks of treatment (weeks 9-12)

• Number of migraine attacks

  From baseline to the last 4 weeks of treatment (weeks 9-12)

• Number of probable migraine attacks

  From baseline to the last 4 weeks of treatment (weeks 9-12)

• Number of 50% responders

  From baseline to the last 4 weeks of treatment (weeks 9-12)

• (Serious) adverse events

  Up to 3 months

Other Outcomes (8)

• Number of 75% responders

  From baseline to the last 4 weeks of treatment (weeks 9-12)

• Number of complete responders

  From baseline to the last 4 weeks of treatment (weeks 9-12)

• Number of acute treatment days

  From baseline to the last 4 weeks of treatment (weeks 9-12)

Study Arms (2)

Ethinylestradiol/levonorgestrel

EXPERIMENTAL

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

Drug: Ethinylestradiol/levonorgestrel

Vitamin E

ACTIVE COMPARATOR

Vitamin E 400 IU oral capsules once daily for 3 months

Drug: Vitamin E

Interventions

Ethinylestradiol/levonorgestrel DRUG

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

Also known as: Microgynon 30, RVG 08204

Ethinylestradiol/levonorgestrel

Vitamin E DRUG

Vitamin E 400 IU oral capsules once daily for 3 months

Vitamin E

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Erasmus Medical Center: collaborator
• Netherlands Brain Foundation: collaborator
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 38360739 DERIVED

MeSH Terms

Conditions

Migraine Disorders

Interventions

Ethinyl Estradiol; Levonorgestrel; Vitamin E

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Norgestrel; Norpregnenes; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Gisela M Terwindt, MD,PhD

  LUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Britt WH van der Arend, MSc

CONTACT

+31715266065; B.W.H.van_der_Arend@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of headache clinic, Principal Investigator

Model Details: Open-label randomized controlled trial

Study Record Dates

• First Submitted: June 28, 2019
• First Posted: July 5, 2019
• Study Start: September 10, 2019
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: December 8, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)