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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 360
- 试验地点
- 1
- 主要终点
- Number of migraine days
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Ethinylestradiol/levonorgestrel
Ethinylestradiol/levonorgestrel 30/150 µg oral tablets once daily without a stopweek for 3 months
干预措施: Ethinylestradiol/levonorgestrel (Drug)
Vitamin E
Vitamin E 400 IU oral capsules once daily for 3 months
干预措施: Vitamin E (Drug)
结局指标
主要结局
Number of migraine days
时间窗: From baseline to the last 4 weeks of treatment (weeks 9-12)
Change in monthly migraine days
次要结局
- Number of headache days(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))
- Number of migraine attacks(From baseline to the last 4 weeks of treatment (weeks 9-12))
- (Serious) adverse events(Up to 3 months)
研究者
G.M. Terwindt, MD
Head of headache clinic, Principal Investigator
Leiden University Medical Center