Condition or disease | Intervention/treatment | Phase |
---|---|---|
Migraine Migraine;Menstrual | Drug: Ethinylestradiol/levonorgestrel Drug: Vitamin E | Phase 3 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 360 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | Open-label randomized controlled trial |
Masking: | None (Open Label) |
Primary Purpose: | Prevention |
Official Title: | 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 |
Actual Study Start Date : | September 10, 2019 |
Estimated Primary Completion Date : | April 2023 |
Estimated Study Completion Date : | April 2023 |
Arm | Intervention/treatment |
---|---|
Experimental: Ethinylestradiol/levonorgestrel
Ethinylestradiol/levonorgestrel 30/150 µg oral tablets once daily without a stopweek for 3 months
|
Drug: Ethinylestradiol/levonorgestrel
Ethinylestradiol/levonorgestrel 30/150 µg oral tablets once daily without a stopweek for 3 months
Other Names:
|
Active Comparator: Vitamin E
Vitamin E 400 IU oral capsules once daily for 3 months
|
Drug: Vitamin E
Vitamin E 400 IU oral capsules once daily for 3 months
|
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Iris E Verhagen, MSc | +31715261730 | I.E.Verhagen@lumc.nl |
Netherlands | |
Leiden University Medical Center | Recruiting |
Leiden, Zuid Holland, Netherlands, 2333 ZA | |
Contact: Coordinating investigator +31715261730 I.E.Verhagen@lumc.nl |
Principal Investigator: | Gisela M Terwindt, MD,PhD | LUMC |
Tracking Information | |||||||
---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | June 28, 2019 | ||||||
First Posted Date ICMJE | July 5, 2019 | ||||||
Last Update Posted Date | February 18, 2021 | ||||||
Actual Study Start Date ICMJE | September 10, 2019 | ||||||
Estimated Primary Completion Date | April 2023 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Number of migraine days [ Time Frame: From baseline to the last 4 weeks of treatment (weeks 9-12) ] Change in monthly migraine days
|
||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
|
||||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures |
|
||||||
Original Other Pre-specified Outcome Measures |
|
||||||
Descriptive Information | |||||||
Brief Title ICMJE | Oral Contraceptive Pill Compared With Vitamin E in Women With Migraine | ||||||
Official Title ICMJE | 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 | ||||||
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. | ||||||
Detailed Description |
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. |
||||||
Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 3 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Open-label randomized controlled trial Masking: None (Open Label)Primary Purpose: Prevention |
||||||
Condition ICMJE |
|
||||||
Intervention ICMJE |
|
||||||
Study Arms ICMJE |
|
||||||
Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||
Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
360 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | April 2023 | ||||||
Estimated Primary Completion Date | April 2023 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
||||||
Sex/Gender ICMJE |
|
||||||
Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE |
|
||||||
Listed Location Countries ICMJE | Netherlands | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT04007874 | ||||||
Other Study ID Numbers ICMJE | WHATT 2018-004096-12 ( EudraCT Number ) |
||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
|
||||||
IPD Sharing Statement ICMJE |
|
||||||
Responsible Party | G.M. Terwindt, MD, Leiden University Medical Center | ||||||
Study Sponsor ICMJE | Leiden University Medical Center | ||||||
Collaborators ICMJE |
|
||||||
Investigators ICMJE |
|
||||||
PRS Account | Leiden University Medical Center | ||||||
Verification Date | February 2021 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |