Migraine DisordersNCT02012790
Nutrition for Migraine Prevention
A study testing Diet in people with Migraine Disorders, run by University of North Carolina, Chapel Hill at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Migraine Disorders
- What is being tested?
- Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 182 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to 11 May 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Able to attend 8 dietitian counseling sessions
- Under care of a physician for headaches
- Able to read and communicate in English
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
UNC Program on Integrative Medicine
Chapel Hill, North Carolina, 27599-7200
About this study
Official title: Clinical & Metabolic Effects of Altering n-3 & n-6 Fatty Acids in Migraine (RCT)
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.
Read the 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:
- 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.
- Conditions
- Migraine Disorders
- Being tested
- Diet
- Keywords
- Migraine disorders
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DietOther
The dietary intervention provides dietary counseling, whole foods (enough for 2 meals and 2 snacks per day) including study oils
| Study group | Role | What they receive |
|---|---|---|
| Diet A | Experimental | Whole food diet modifies dietary fatty acids. Foods provided for 16 weeks; study oils provided for 22 weeks. Receives: Other: Diet |
| Diet B | Experimental | Whole food diet modifies dietary fatty acids. Foods provided for 16 weeks; study oils provided for 22 weeks. Receives: Other: Diet |
| Diet C | Active comparator | Whole food diet modifies dietary fatty acids. Foods provided for 16 weeks; study oils provided for 22 weeks. Receives: Other: Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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"
Measured: Change in HIT-6 at 16 weeks
Secondary outcomes (4)
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.
Measured: 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
Measured: 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).
Measured: 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)
Measured: Trajectory of change pre-intervention, 0-16 weeks, and 16-22 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2013 (estimated)
- Study startJul 2014
- Primary completion29 Mar 2018
- Study completion11 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Migraine DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 182 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Sponsor
- Investigators
- John D Mann, MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02012790
- Sponsor's protocol ID
- 13-3284
- Other IDs
- UL1TR000083, 1R01AT007813-01A1
- Status last verified
- Oct 2020
- First submitted
- 5 Nov 2013
- Last updated
- 6 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Faurot KR, Park J, Miller V, Honvoh G, Domeniciello A, Mann JD, Gaylord SA, Lynch CE, Palsson O, Ramsden CE, MacIntosh BA, Horowitz M, Zamora D. Dietary fatty acids improve perceived sleep quality, stress, and health in migraine: a secondary analysis of a randomized controlled trial. Front Pain Res (Lausanne). 2023 Oct 25;4:1231054. doi: 10.3389/fpain.2023.1231054. eCollection 2023.
PubMed 37954068Ramsden CE, Zamora D, Faurot KR, MacIntosh B, Horowitz M, Keyes GS, Yuan ZX, Miller V, Lynch C, Honvoh G, Park J, Levy R, Domenichiello AF, Johnston A, Majchrzak-Hong S, Hibbeln JR, Barrow DA, Loewke J, Davis JM, Mannes A, Palsson OS, Suchindran CM, Gaylord SA, Mann JD. Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial. BMJ. 2021 Jun 30;374:n1448. doi: 10.1136/bmj.n1448.
PubMed 34526307Miller VE, Faurot KR, Palssson OS, MacIntosh BA, Suchindran C, Honvoh G, Gaylord S, Ramsden CE, Mann JD. Comparing prospective headache diary and retrospective four-week headache questionnaire over 20 weeks: Secondary data analysis from a randomized controlled trial. Cephalalgia. 2020 Nov;40(13):1523-1531. doi: 10.1177/0333102420949180. Epub 2020 Aug 16.
PubMed 32799667Mann JD, Faurot KR, MacIntosh B, Palsson OS, Suchindran CM, Gaylord SA, Lynch C, Johnston A, Maiden K, Barrow DA, Hibbeln JR, Ramsden CE. A sixteen-week three-armed, randomized, controlled trial investigating clinical and biochemical effects of targeted alterations in dietary linoleic acid and n-3 EPA+DHA in adults with episodic migraine: Study protocol. Prostaglandins Leukot Essent Fatty Acids. 2018 Jan;128:41-52. doi: 10.1016/j.plefa.2017.11.002. Epub 2017 Nov 16.
PubMed 29413360
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical & Metabolic Effects of Altering n-3 & n-6 Fatty Acids in Migraine (RCT)
- ClinicalTrials.gov ID
- NCT02012790
- Acronym / sponsor ID
- 13-3284
- Conditions
- Migraine Disorders
- Keywords
- Migraine disorders
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 182 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Study start
- Jul 2014
- Primary completion
- 29 Mar 2018 (actual)
- Study completion
- 11 May 2018 (actual)
- First posted
- 16 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Diet A | Experimental | Other: DietWhole food diet modifies dietary fatty acids. Foods provided for 16 weeks; study oils provided for 22 weeks. |
| Diet B | Experimental | Other: DietWhole food diet modifies dietary fatty acids. Foods provided for 16 weeks; study oils provided for 22 weeks. |
| Diet C | Active comparator | Other: DietWhole food diet modifies dietary fatty acids. Foods provided for 16 weeks; study oils provided for 22 weeks. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DietThe dietary intervention provides dietary counseling, whole foods (enough for 2 meals and 2 snacks per day) including study oils | Other | Diet A, Diet B, Diet C |
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"
4 secondary outcomes
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)
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
17-hydroxy DHA trajectory
Time frame: Trajectory of change in 17-hydroxy DHA 0-16 weeks and 16-22 weeks
HIT-6
Time frame: Trajectory of change pre-intervention, 0-16 weeks, and 16-22 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2020.
- Derived from this study: PubMed 37954068Faurot KR, Park J, Miller V, Honvoh G, Domeniciello A, Mann JD, Gaylord SA, Lynch CE, Palsson O, Ramsden CE, MacIntosh BA, Horowitz M, Zamora D. Dietary fatty acids improve perceived sleep quality, stress, and health in migraine: a secondary analysis of a randomized controlled trial. Front Pain Res (Lausanne). 2023 Oct 25;4:1231054. doi: 10.3389/fpain.2023.1231054. eCollection 2023.
- Derived from this study: PubMed 34526307Ramsden CE, Zamora D, Faurot KR, MacIntosh B, Horowitz M, Keyes GS, Yuan ZX, Miller V, Lynch C, Honvoh G, Park J, Levy R, Domenichiello AF, Johnston A, Majchrzak-Hong S, Hibbeln JR, Barrow DA, Loewke J, Davis JM, Mannes A, Palsson OS, Suchindran CM, Gaylord SA, Mann JD. Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial. BMJ. 2021 Jun 30;374:n1448. doi: 10.1136/bmj.n1448.
- Derived from this study: PubMed 32799667Miller VE, Faurot KR, Palssson OS, MacIntosh BA, Suchindran C, Honvoh G, Gaylord S, Ramsden CE, Mann JD. Comparing prospective headache diary and retrospective four-week headache questionnaire over 20 weeks: Secondary data analysis from a randomized controlled trial. Cephalalgia. 2020 Nov;40(13):1523-1531. doi: 10.1177/0333102420949180. Epub 2020 Aug 16.
- Derived from this study: PubMed 29413360Mann JD, Faurot KR, MacIntosh B, Palsson OS, Suchindran CM, Gaylord SA, Lynch C, Johnston A, Maiden K, Barrow DA, Hibbeln JR, Ramsden CE. A sixteen-week three-armed, randomized, controlled trial investigating clinical and biochemical effects of targeted alterations in dietary linoleic acid and n-3 EPA+DHA in adults with episodic migraine: Study protocol. Prostaglandins Leukot Essent Fatty Acids. 2018 Jan;128:41-52. doi: 10.1016/j.plefa.2017.11.002. Epub 2017 Nov 16.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John D Mann, MD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Diet in people with Migraine Disorders, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary metabolic outcome: 17-hydroxy docosahexaenoic acid (DHA) (time frame: Change in 17-hydroxy DHA at 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02012790, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2020.