Nutrition for Migraine Prevention

Migraine Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02012790
• Other study ID #: 13-3284
• Secondary ID: UL1TR0000831R01A
• Status: Completed
• Phase: N/A
• Start date: July 2014
• Est. completion date: May 11, 2018

Study information

• Verified date: October 2020
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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:

1. To assess the efficacy of the dietary interventions in inducing the predicted changes in circulating fatty acid endovanilloid derivatives;

2. To compare the clinical effects in migraine specific outcomes of two 16-week analgesic dietary interventions with each other and a control diet;

3. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 182
• Est. completion date: May 11, 2018
• Est. primary completion date: March 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Migraine Disorders

Intervention

Other:
• Diet
The dietary intervention provides dietary counseling, whole foods (enough for 2 meals and 2 snacks per day) including study oils

Locations

Country	Name	City	State
United States	UNC Program on Integrative Medicine	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Center for Complementary and Integrative Health (NCCIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Migraine Disability Assessment Score (MIDAS)	Disability, defined as the consequences of illness on ability to work and function, will be measured using the headache disability assessment score (MIDAS). Derived from the Headache Impact Test, MIDAS is a 7-item questionnaire that assesses the number of days during the previous three months that respondents missed work or school, experienced decreased productivity at work or home, or missed social engagements because of headaches. Test-retest reliability is acceptable, with Spearman's correlation coefficient ranging from 0.67 to 0.73. Cronbach's alpha is 0.83	Change in MIDAS from randomization to 16 weeks after randomization
Other	Medication use for treatment of headache.	Subjects enter number of doses of medications used for treatment of headaches into their daily diaries.	trajectory of change over 16 weeks
Other	Unusual symptoms	Subjects will record unusual symptoms in a comment field in their daily diaries.	Daily for 4 weeks before randomization, and 22 weeks after randomization
Primary	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	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	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)
Secondary	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
Secondary	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
Secondary	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