Temporal, Environmental, and Genetic Factors Regulating Exercise and Migraine
Condition: Migraine Disorders
MeSH terms: Migraine Disorders
Study type: Interventional

Summary: 
      Chronic pain, of which migraine is among the most common, affects 100 million US adults and
      costs between $560 to $635 billion dollars annually. There is a need for effective, low-cost
      non-pharmacological strategies to reduce migraine load in migraineurs (based on International
      Headache Society classification International Classification of Headache Disorders [ICHD]-3;
      experience headache [migraine-like or tension-type-like] on 15+ days/month for 3+ months, and
      have migraine headaches [either with aura or without aura] on 8+ days/month). This represents
      an area of interest, as common migraine medications induce central nervous system
      side-effects including aphasia, ataxia, somnolescence, and vertigo; and 79% of suffers have
      an interest in trying novel treatment strategies with lower adverse effects than medications.

      Exercise has been shown to be a non-pharmacological intervention to reduce migraine burden.
      However, how environmental (i.e. - time-of-day, exposure to nature) and genetic factors (i.e.
      - polymorphisms in circadian and migraine associated genes) impact the laudatory effects of
      exercise remains unknown. There are independently established heritable components to
      migraine frequency (65%), circadian rhythm (70%), and aerobic power during exercise (66%).
      Thus, the central hypothesis is that an optimal environment can improve the exercise-induced
      reduction in migraine load, which is influenced by genetic heritability of migraine related
      gene polymorphisms.
    

Detailed description: 
      Willing participants who are self-reported chronic migraineurs will complete an informed
      consent followed by a health risk questionnaire to determine study eligibility.

      Phase I: Chronic migraineurs will be screened using the Morningness/Eveningness Questionnaire
      (MEQ) to recruit a cohort of discrepant chronotypes (Definite Morning, Morning; and Evening,
      Definite Evening). Resulting participants will be complete a baseline migraine load
      evaluation and assigned to four weeks of moderate intensity exercise (60-70% estimated heart
      rate max, 2 x per week, 30-min/session) consolidated to either the morning (before 09:00) or
      afternoon (after 17:00) in a randomized cross-over design. Intensity will be tracked through
      a heart rate monitor that will be provided to participants, and an application that they can
      download to their phone. Participants will be able to keep the heart rate monitor upon
      completion of the study. An example of potential exercises will be provided to participants
      and research team members will check in every 1-2 weeks to see how exercise is progressing.
      Migraine burden will be assessed pre- and post-training after each condition using the
      Migraine Disability Assessment (MIDAS) and the short version of the Headache Impact Test
      (HIT-6). Half of the participants will exercise for one month during a time of day that is in
      sync with their chronotype (i.e. Morning type person will exercise in the morning), and the
      other half of the participants will exercise at a time of day that is not in sync (i.e.
      Morning type person will exercise in the evening). There will be a one-month wash out period,
      and then participants will complete training at the other time of day. A buccal swab will be
      obtained (according to protocols outlined on our approved Institutional Biosafety Committee
      protocol) for phenotyping of genes specific to chronotype and migraine.

      Phase II will also recruit chronic ICHD-3 migraineurs. Participants will complete a baseline
      migraine load evaluation as described above. If an effect of chronotype is found in Phase I,
      participants will complete exercise training in sync with their chronotype. Participants will
      be randomly assigned to four weeks of moderate intensity aerobic exercise (60-70% estimated
      heart rate max, 2 x per week, 30-min/session) in either natural or indoor environments in a
      randomized cross-over design. Intensity will be tracked through a heart rate monitor that
      will be provided to participants, and an application that they can download to their phone.
      Participants will be able to keep the heart rate monitor upon completion of the study. An
      example of potential exercises will be provided to participants and research team members
      will check in every 1-2 weeks to see how exercise is progressing. A recent investigation
      provided evidence that activity performed in a desert environment provided the same benefits
      as in a green landscape with respect to both cardiovascular measures as well as perception of
      comfort, calm, and perceived stress. Half of the participants will exercise for one month in
      a natural environment that they select (outdoors in a park, or trail) and the other half will
      complete exercise indoors (participants will not require access to fitness facilities,
      although these could be used if they are already a member). There will be a one month wash
      out period, and then participants will complete exercise training in the other setting.
      Change in the monthly migraine load will be determined between environments. A buccal swab
      will be obtained for phenotyping of genes specific to chronotype and migraine.

      Buccal swab samples will be used to isolate DNA. Isolated DNA will be genotyped at the
      University of Nevada, Las Vegas (UNLV) Genomics Core Facility using polymerase chain reaction
      and then disposed of. Genotypes will be linked to participant migraine load responses, and
      then reported in aggregate.

      The investigators plan to maintain regular contact with participants. After each exercise
      bout, participants will download and email the associated csv file which will be received,
      deidentified, and labelled with the participant identification number for digital storage at
      UNLV. In response, participants will be asked about the exercise sessions (with open ended
      questions such as "How do you feel the exercise sessions are going?"). The file will be
      reviewed upon receipt by a member of the research team to determine exercise intensity
      (60-70% estimated heart rate range), allow the investigators to provide feedback, and also
      enable the determination of how well participants are adhering to the intervention. The
      investigators will use the Polar Flow application (available for free), which can be deleted
      by the participant at the end of the study if they so choose.
    

Intervention name(s): Chronotype; Green exercise
Intervention type(s): Behavioral; Behavioral
Intervention description(s): Participants screened using the Morningness/Eveningness Questionnaire. Chronotype categorized as either Definite Morning/Morning, or Evening/Definite Evening. Participant will exercise (60-70% estimated heart rate max, 2 x per week, 30-min/session) either in sync or not in sync with chronotype for one month in a randomized cross-over design. There will be a one-month wash out period, and then participant will complete training in the alternate chronotype for one month.; Participants will be randomly assigned to four weeks of moderate intensity aerobic exercise (60-70% estimated heart rate max, 2 x per week, 30-min/session) in either natural or indoor environments in a randomized cross-over design. There will be a one-month wash out period, and then participant will complete training in alternate environment for one month.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Randomized crossover design
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronotype; Green exercise