Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Nutrition for Migraine Prevention

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02012790
Recruitment Status : Completed
First Posted : December 16, 2013
Last Update Posted : October 6, 2020
Sponsor:
Collaborator:
National Center for Complementary and Integrative Health (NCCIH)
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Tracking Information
First Submitted Date  ICMJE November 5, 2013
First Posted Date  ICMJE December 16, 2013
Last Update Posted Date October 6, 2020
Study Start Date  ICMJE July 2014
Actual Primary Completion Date March 29, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 10, 2013)
  • 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 Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 21, 2014)
  • 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 Measures  ICMJE
 (submitted: December 10, 2013)
  • 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)
Current Other Pre-specified Outcome Measures
 (submitted: December 10, 2013)
  • Migraine Disability Assessment Score (MIDAS) [ Time Frame: Change in MIDAS from randomization to 16 weeks after randomization ]
    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
  • Medication use for treatment of headache. [ Time Frame: trajectory of change over 16 weeks ]
    Subjects enter number of doses of medications used for treatment of headaches into their daily diaries.
  • Unusual symptoms [ Time Frame: Daily for 4 weeks before randomization, and 22 weeks after randomization ]
    Subjects will record unusual symptoms in a comment field in their daily diaries.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Nutrition for Migraine Prevention
Official Title  ICMJE 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Migraine Disorders
Intervention  ICMJE Other: Diet
The dietary intervention provides dietary counseling, whole foods (enough for 2 meals and 2 snacks per day) including study oils
Study Arms  ICMJE
  • Experimental: Diet A
    Whole food diet modifies dietary fatty acids. Foods provided for 16 weeks; study oils provided for 22 weeks.
    Intervention: Other: Diet
  • Experimental: Diet B
    Whole food diet modifies dietary fatty acids. Foods provided for 16 weeks; study oils provided for 22 weeks.
    Intervention: Other: Diet
  • Active Comparator: Diet C
    Whole food diet modifies dietary fatty acids. Foods provided for 16 weeks; study oils provided for 22 weeks.
    Intervention: Other: Diet
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 28, 2018)
182
Original Estimated Enrollment  ICMJE
 (submitted: December 10, 2013)
153
Actual Study Completion Date  ICMJE May 11, 2018
Actual Primary Completion Date March 29, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02012790
Other Study ID Numbers  ICMJE 13-3284
UL1TR000083 ( U.S. NIH Grant/Contract )
1R01AT007813-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of North Carolina, Chapel Hill
Study Sponsor  ICMJE University of North Carolina, Chapel Hill
Collaborators  ICMJE National Center for Complementary and Integrative Health (NCCIH)
Investigators  ICMJE
Principal Investigator: John D Mann, MD University of North Carolina, Chapel Hill
PRS Account University of North Carolina, Chapel Hill
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP