Clinical Trial: Nutrition for Migraine Prevention

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief Summary:

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 Summary:

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.

Current Primary Outcome:

• Primary metabolic outcome: 17-hydroxy docosahexaenoic acid (DHA) [ Time Frame: Change in 17-hydroxy DHA at 16 weeks ]
  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.
• Primary clinical outcome: Headache-specific Quality of Life (HIT-6) [ Time Frame: Change in HIT-6 at 16 weeks ]
  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"

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Headache hours per day (headache frequency) are measured by a daily Headache Diary [ Time Frame: Trajectory of change: -4 to 0 weeks (pre-intervention), 0-16 weeks (intervention), and 16-22 weeks (post-intervention) ]
  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.
• Patient-Reported Outcomes Measurement Information System-29 Profile [ Time Frame: Pre-post and trajectory of change measured at randomization and at 4,10, and 16 weeks after randomization ]
  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
• 17-hydroxy DHA trajectory [ Time Frame: Trajectory of change in 17-hydroxy DHA 0-16 weeks and 16-22 weeks ]
  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).
• HIT-6 [ Time Frame: Trajectory of change pre-intervention, 0-16 weeks, and 16-22 weeks ]
  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)

Original Secondary Outcome:

• Headache hours per day (headache frequency) are measured by a daily Headache Diary [ Time Frame: Trajectory of change: -4 to 0 weeks (pre-intervention), 0-16 weeks (intervention), and 16-22 weeks (post-intervention) ]
  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. For those subjects unwilling to use electronic diaries, postage pre-paid envelopes will be provided. Numbers of hours of any headache will be calculated along with numbers of hours of moderate to severe headache for use in longitudinal models.
• Patient-Reported Outcomes Measurement Information System-29 Profile [ Time Frame: Pre-post and trajectory of change measured at randomization and at 4,10, and 16 weeks after randomization ]
  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
• 17-hydroxy DHA trajectory [ Time Frame: Trajectory of change in 17-hydroxy DHA 0-16 weeks and 16-22 weeks ]
  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).
• HIT-6 [ Time Frame: Trajectory of change pre-intervention, 0-16 weeks, and 16-22 weeks ]
  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)

Dates:
Date Received: November 5, 2013
Date Started: July 2014
Date Completion: June 2018
Last Updated: May 10, 2016
Last Verified: May 2016