Omega-3 Fatty Acid in the Prevention of Migraine

Study Overview
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Brief Summary
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To understand the clinical efficacy for omega-3 PUFAs migraine prevention.To uncover the underlying biochemical or neurophysiological mechanisms by which omega-3 PUFAs for migraine prevention.

Detailed Description
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Background: Migraine is a common disabling disorder and its substantial burden is associated with considerable negative impact on quality of life. Several pharmacological treatments are available for migraine prophylaxis but insufficient efficacy and significant side effects preclude their widely use for migraine treatment. In recent years, more attention has been paid to dietary supplements and natural ingredients for the treatment of migraine. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have beneficial on the reduction of neurogenic, perivascular inflammations and pro-inflammatory cytokines, which may play an important role in the pathophysiology of migraine. However, the results of investigations carried out about the clinical efficacy of omega-3 PUFAs in the management of migraine are inconsistent. Purpose: To understand the clinical efficacy for omega-3 PUFAs migraine prevention. To uncover the underlying biochemical or neurophysiological mechanisms by which omega-3 PUFAs for migraine prevention Method: This two-year project includes clinical approaches to investigate the therapeutic effects of omega-3 PUFAs on episodic migraine (4-14 days/month) without migraine preventive treatment in the past one month. 120 patients, aged 20-65, will be randomized in a 12-week, double-blind, placebo-controlled trial comparing the effects of high-dose eicosapentaenoic acid (EPA, 1.8g/day) and placebo intervention. All participants will complete a set of outcome measures: headache questionnaires and headache diary, the Migraine Disability Assessment (MIDAS), patient overall impression questionnaire-migraine improvement questionnaire (PGI-I), patient overall impression questionnaire-migraine severity questionnaire (PGI-S), Beck Depression Inventory-II (BDI-II), Hospital anxiety and depression scale (HADS), Migraine Quality of Life Questionnaire (MSQ), Pittsburgh Sleep Quality Questionnaire (PSQI) at baseline and the follow-up visits before and after 12 weeks of placebo or omega-3 PUFAs intervention (EPA, 1.8 g/day) and a series of blood tests for neurotransmitter, neurotrophic and neuroinflammation. The clinical efficacy and the peripheral blood biomarkers, will be analyzed at baseline and the end of the intervention. Expected results: To establish the clinical evidence of omega-3 PUFAs on migraine prevention. To provide significant insights into molecular actions of omega-3 PUFAs on migraine prevention.

Official Title
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Omega-3 Fatty Acid in the Prevention of Migraine: From the Randomized Clinical Trial to Molecular Biology Approaches

Conditions
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Migraine, Omega-3 Polyunsaturated Fatty Acids

Intervention / Treatment
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* Dietary Supplement: Omega-3 polyunsaturated fatty acids
* Dietary Supplement: omega-6 PUFAs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 20 to 65 years old A diagnosis based on the International Classification of Headache Disorders (ICHD-3) An established migraine history for at least 1 year Independent from the study Written informed consent Exclusion Criteria: Chronic migraine Headaches other than migraine Use any of the following drugs in the past four weeks： Migraine prophylaxis agents Anti-depressants Calcium channel blockers Anti-epileptic agents Cycle-modulating hormonal drugs Onabotulinumtoxin A (Botox) injection Migraine onset after the age of 50 Emerging abnormal findings on： Laboratory parameters Physical examination Suicidal risks Severe depression Cognitive impairment Allergies or hypersensitivity to fish or omega-3 fatty acids Bleeding diathesis or using anticoagulation agents Pregnancy or nursing

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>All participants will complete a set of outcome measures at baseline and the follow-up visits before and after 12 weeks of placebo omega-6 PUFAs intervention and a series of blood tests for neurotransmitter, neurotrophic and neuroinflammation. The clinical efficacy and the peripheral blood biomarkers, will be analyzed at baseline and the end of the intervention. | Dietary Supplement: omega-6 PUFAs<br>* All participants will complete a set of outcome measures at baseline and the follow-up visits before and after 12 weeks of placebo omega-6 PUFAs intervention and a series of blood tests for neurotransmitter, neurotrophic and neuroinflammation. The clinical efficacy and the peripheral blood biomarkers, will be analyzed at baseline and the end of the intervention.<br>|
| Experimental: Omega-3<br>All participants will complete a set of outcome measures at baseline and the follow-up visits before and after 12 weeks of omega-3 PUFAs intervention (EPA) and a series of blood tests for neurotransmitter, neurotrophic and neuroinflammation. The clinical efficacy and the peripheral blood biomarkers, will be analyzed at baseline and the end of the intervention. | Dietary Supplement: Omega-3 polyunsaturated fatty acids<br>* All participants will complete a set of outcome measures at baseline and the follow-up visits before and after 12 weeks of omega-3 PUFAs intervention (EPA, 1.8 g/day) and a series of blood tests for neurotransmitter, neurotrophic and neuroinflammation. The clinical efficacy and the peripheral blood biomarkers, will be analyzed at baseline and the end of the intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of migraine attacks during the 12-week period [Efficacy] | The primary end point is the mean change from baseline (28-day pretreatment period) in the mean number of monthly migraine days during the 12-week period. A migraine day was defined as (a day with headache pain that lasted 4 hours with a peak severity of moderate or severe intensity, or any severity or duration if the participant took and responded to a triptan or ergot) from the second to the fourth diaries compared with the first diary (baseline period). | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 50% reduction of migraine attacks | 50% reduction in the the average migraine attacks per month during the 12-week period from baseline (28-day pretreatment period). | 12 weeks | 
| Migraine Disability Assessment Score (MIDAS) | Change of MIDAS scores from baseline to endpoint. | 12 weeks | 
| Hospital Anxiety and Depression Scale (HADS) | Change of HADS scores from baseline to endpoint. | 12 weeks | 
| The Patient Global Impression of Improvement (PGI-I) and Patient Global Impression of Severity (PGI-S) | Change of PGI-I and PGI-S scores from baseline to endpoint. | 12 weeks | 
| The Beck Depression Inventory-II (BDI-II) | Change of BDI-II scores from baseline to endpoint. | 12 weeks | 
| Reduction of acute headache medications | Reduction from baseline in the number of days with acute headache medications, from the second to the fourth diaries compared with the first diary (baseline period). | 12 weeks | 
| Reduction of accumulative headache hours | Reduction in accumulative headache hours from the second to the fourth diaries compared with the first diary (baseline period). | 12 weeks | 
| Migraine Quality of Life Questionnaire (MSQ) scores | Change of Migraine Quality of Life Questionnaire (MSQ) scores from baseline to endpoint. | 12 weeks | 
| Pittsburgh Sleep Quality Questionnaire (PSQI) scores | Change of Pittsburgh Sleep Quality Questionnaire (PSQI) scores from baseline to endpoint. | 12 weeks |