Nutrition for Migraine Prevention

Study Overview
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Brief Summary
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Migraine is a widespread, debilitating, chronic pain disorder and a major public health challenge. Most conventional, pharmaceutical treatments fail to give satisfactory long-term relief and their repeated use can have important side effects. This project involves implementation of substantial dietary changes in adults with migraine. Our goal is to test the hypothesis that a causal relationship exists between migraine symptoms and the amount and proportions of foods consumed containing defined amounts of polyunsaturated fatty acids. Significant findings supporting the hypothesis will lead to a major shift in both prevention and management of migraine and other chronic pain disorders. Emphasis is on low-cost, health improvement strategies utilizing specific dietary modifications for pain management, based on solid clinical research evidence.

Detailed Description
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Episodic migraine is a debilitating chronic pain condition afflicting 12% of American adults. Current conventional treatments rely on medications that provide limited or transient relief, target symptoms rather than the underlying causes of pain, and are associated with significant side effects and costs. It is therefore essential to investigate non-pharmacologic approaches to conventional headache treatments. Certain fatty acids and their bioactive metabolites regulate multiple pain-related biochemical pathways. Controlled clinical trials investigating pain modulation in response to dietary changes while exploring relevant mechanisms of action in humans are lacking. In a recent feasibility study in patients with chronic daily headache (CDH), we found that targeted fatty acid modifications altered circulating endovanilloids, while reducing headache frequency and improving quality of life. These findings support our proposed model in which diet-induced alterations in endovanilloids modulate transient receptor potential cation channel subfamily V member 1 (TRPV1) activity in vivo, leading to important implications for migraine and chronic pain in general. The goal of this research is to assess whether dietary PUFA modifications can result in predicted changes in circulating endovanilloids and improvement in headache-related clinical outcomes. The proposed 3-arm, 26-week,randomized, controlled, single-blind trial, with 51 subjects in each group, includes a 4-week baseline of usual care, followed by randomization to one of three 22-week dietary interventions plus usual care. Each of the three arms involves specific modifications of dietary fatty acid intakes through a whole foods diet. Participants in the dietary interventions receive food sufficient for 2 meals and 2 snacks daily along with extensive dietary counseling. Specific aims are: To assess the efficacy of the dietary interventions in inducing the predicted changes in circulating fatty acid endovanilloid derivatives; To compare the clinical effects in migraine specific outcomes of two 16-week analgesic dietary interventions with each other and a control diet; To test, in an exploratory manner, our model of the proposed causal chain linking changes in fatty acids, their endovanilloid derivatives, and headache clinical endpoints. This proposal utilizes an innovative design and hypotheses to address current research funding priorities, by examining clinical efficacy and underlying mechanisms of a promising dietary manipulation with the distinct potential for high impact in terms of ameliorating a chronic, disabling pain disorder.

Official Title
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Clinical & Metabolic Effects of Altering n-3 & n-6 Fatty Acids in Migraine (RCT)

Conditions
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Migraine Disorders

Intervention / Treatment
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* Other: Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Either gender Meets 2004 International Classification of Headache Disorders-II* criteria for Episodic Migraine Frequent migraine headaches Headache history: > 2 years leading up to study meeting migraine criteria Willing to complete daily diary for 26 weeks Able to attend 8 dietitian counseling sessions Under care of a physician for headaches Able to read and communicate in English Exclusion Criteria: Marked depression, anxiety or psychosis. History of specific food allergies, such as, but not limited to, dairy or gluten products Pregnancy or anticipated pregnancy Active treatment for a major medical illness, such as malignancy, autoimmune, immune deficiency disorder, etc. History of significant head trauma or head/neck surgery within the past 3 years History of subarachnoid or intra-cerebral hemorrhage or subdural hematoma Allergy to fish or strong aversion to fish consumption. History of nervous system infection such as meningitis or encephalitis within the preceding 5 years History of vasculitis, intracranial mass, clotting disorder Cognitive dysfunction that would prevent informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Experimental: Diet A<br>Whole food diet modifies dietary fatty acids. Foods provided for 16 weeks; study oils provided for 22 weeks. | Other: Diet<br>* The dietary intervention provides dietary counseling, whole foods (enough for 2 meals and 2 snacks per day) including study oils<br>|
| Experimental: Diet B<br>Whole food diet modifies dietary fatty acids. Foods provided for 16 weeks; study oils provided for 22 weeks. | Other: Diet<br>* The dietary intervention provides dietary counseling, whole foods (enough for 2 meals and 2 snacks per day) including study oils<br>|
| Active Comparator: Diet C<br>Whole food diet modifies dietary fatty acids. Foods provided for 16 weeks; study oils provided for 22 weeks. | Other: Diet<br>* The dietary intervention provides dietary counseling, whole foods (enough for 2 meals and 2 snacks per day) including study oils<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary metabolic outcome: 17-hydroxy docosahexaenoic acid (DHA) | 17-hydroxy DHA is the pathway marker and precursor to two families of potent bioactive mediators with analgesic properties (D series resolvins and protectins), which will be measured at baseline and after 16 weeks of diet exposure. | Change in 17-hydroxy DHA at 16 weeks | 
| Primary clinical outcome: Headache-specific Quality of Life (HIT-6) | The HIT-6 is a validated questionnaire designed to measure the impact that headaches have on the ability to function on the job, at school, at home, and in social situations | Change in HIT-6 at 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache hours per day (headache frequency) are measured by a daily Headache Diary | Subjects will be instructed to maintain a daily record of their headaches using a headache diary. Subjects will be asked to record the frequency, intensity, and duration of their headaches by rating their headaches hourly as none, mild, moderate and severe. Hours of sleep will also be indicated. In our clinical trial of a migraine headache treatment, subjects were willing and able to complete daily diaries with minimal loss of data. Diaries will be completed on a secure website via a computer or smart-phone interface. Numbers of hours of any headache will be calculated along with numbers of hours of moderate to severe headache for use in longitudinal models. | Trajectory of change: -4 to 0 weeks (pre-intervention), 0-16 weeks (intervention), and 16-22 weeks (post-intervention) | 
| Patient-Reported Outcomes Measurement Information System-29 Profile | This battery of short instruments covers the following domains associated with chronic pain: physical function, anxiety, depression, fatigue, sleep disturbance, satisfaction with social role, pain interference, and pain intensity | Pre-post and trajectory of change measured at randomization and at 4,10, and 16 weeks after randomization | 
| 17-hydroxy DHA trajectory | 17-hydroxy DHA is the pathway marker and precursor to two families of potent bioactive mediators with analgesic properties (D series resolvins and protectins), which will be measured at baseline, after 4, 10, and 16 weeks of diet exposure, and at the end of the observation period (22 weeks). | Trajectory of change in 17-hydroxy DHA 0-16 weeks and 16-22 weeks | 
| HIT-6 | The HIT-6 is a validated questionnaire designed to measure the impact that headaches have on the ability to function on the job, at school, at home, and in social situations measured at baseline, randomization, and after 4,10, and 16 weeks on the diet and at the end of the observation period (22 weeks) | Trajectory of change pre-intervention, 0-16 weeks, and 16-22 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine disorders