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NCT Number: NCT07573488

Sleep, Stress and Migraine - an Observational and Training Study

The MiSleepS study investigates how sleep disturbances and stress are linked to migraine attacks. Participants wear a device called a WHOOP band, which tracks sleep and body signals, and answer brief daily questions via a smartphone app about their sleep, stress levels, and migraine symptoms. The goal is to identify personal patterns that may contribute to migraine. Based on these insights, participants receive individualized recommendations to improve their sleep and daily routines - aiming to reduce migraine attacks in the long term without medication. The study is conducted at the University Hospital Zurich and is aimed at adults with episodic migraine.

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Key information

Conditions

Migraine Behavior Brain Diseases Central Nervous System Diseases Headache Disorders Headache Disorders, Primary Health Behavior Mental Disorders Migraine Disorders Migraine in Adults Nervous System Diseases Neurologic Manifestations Pathological Conditions, Signs and Symptoms Signs and Symptoms Sleep Disorder (Disorder) Sleep Hygiene Sleep Wake Disorders Stress

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

Migraine is a widespread neurological disorder affecting more than one billion people worldwide, and is among the leading causes of disability, particularly in women. It is characterized by episodic or chronic headaches and often accompanied by nausea, photophobia, and cognitive impairment. Despite advances in pharmacological therapies - such as the advent of CGRP antagonists - a large proportion of patients remain undertreated or refractory to standard interventions. Critically, migraine is influenced by multiple behavioral and environmental triggers, among which sleep disturbances and stress are consistently among the most frequently reported and most modifiable. However, their complex and often bidirectional interactions with migraine are still not fully understood, and most available research is limited by methodological constraints, including short observation periods, retrospective data, and insufficient attention to sex and gender variables.

The Migraine Sleep Study (MiSleepS) is a prospective, two-phase clinical study aiming to investigate the role of sleep, circadian rhythm, and stress as dynamic triggers of migraine and to evaluate the effectiveness of individualized, non-pharmacological behavioral interventions. Conducted at the University Hospital Zurich, this monocentric study will combine high-resolution physiological data captured via the WHOOP 5.0 wrist-worn wearable device with real-time, ecological momentary assessments (EMA) collected through the SEMA3 smartphone app. These dual digital tools enable continuous monitoring of key variables such as sleep duration, sleep architecture, heart rate variability, perceived stress, and migraine occurrence and severity.

Participants will undergo a five-week observational phase (phase A), during which their natural sleep-stress-migraine interactions will be captured without interference. An interim analysis will be conducted to identify individual behavioral and circadian profiles, including insomnia-like patterns, sleep deprivation, social jetlag, and chronotype mismatch. Based on these results, participants will be stratified into clusters and assigned a tailored behavioral plan to address their specific profile. In the subsequent six-week intervention phase (phase B), participants will implement these behavioral strategies, supported by remote follow-ups and daily app-based tracking. The primary endpoint will be the change in monthly migraine days, while secondary endpoints include migraine severity, sleep quality, stress levels, and adherence to recommendations.

To control for observation-related confounding - such as the Hawthorne effect - a run-in cohort of the first ten participants will follow a modified protocol. While they undergo the same assessment and tracking procedures, they will not receive any behavioral recommendations in phase B. This approach allows for differentiation between improvements due to heightened self-awareness and those attributable to the targeted intervention itself.

The study further aims to examine sex- and gender-related differences in migraine pathophysiology and response to behavioral interventions, using validated tools such as the Stanford Gender-Related Variables for Health Research (GVHR) score (Nielsen et al., 2021). By integrating physiological, psychological, and gender-related dimensions, MiSleepS aspires to develop a more individualized understanding of migraine and to explore scalable, low-risk, non-pharmacological treatment strategies that can be implemented in clinical practice.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults aged between 18 and 65 years
  • Diagnosis of episodic migraine according to The International Classification of Headache Disorders (ICHD-3) criteria confirmed by our headache specialists
  • 4 to 14 headache days per month (mean value based on the 3 months prior to study enrollment)
  • Ability to give informed consent and to adhere to the study protocol
  • Sufficient German language comprehension to follow the study procedures and answer all questions related to the study outcomes
  • Stable migraine medication regimen for the past 3 months and throughout the study period

Exclusion criteria

  • Diagnosis of sleep disorders that could interfere with the sleep intervention, such as obstructive sleep apnea with an apnea-hypopnea index (AHI) > 15, Restless Legs Syndrome, frequent (i.e. weekly) Non-rapid eye movement (NREM) sleep parasomnia, REM Behavior Disorder (RBD)
  • Current diagnosis of a psychiatric disorder that is inadequately treated or therapy-resistant and may interfere with study participation or adherence to study procedures (this includes, but is not limited to: schizophrenia, schizoaffective disorder, bipolar disorder (type I), post-traumatic stress disorder with active symptoms, or major depressive disorder with ongoing functional impairment despite treatment). Diagnosis must be confirmed by clinical history or treating physician.
  • Regular use of benzodiazepines and other central nervous system (CNS)-depressant substances (self-reported)
  • Concomitant steroid medication (self-reported)
  • Known or suspected alcohol, drug or medication abuse (i.e. > 0.5 l wine or 1 l beer per day)
  • Inability to follow the procedures of the study (e.g., due to language problems, cognitive deficits, instable home situation)
  • Concurrent participation in another study involving drug and behavioral interventions within 3 months prior to and during the present study, as well as participation in an ongoing study with data collection through SEMA3
  • Planned medical intervention of substantial relevance requiring hospitalization for more than 24 hours (e.g. surgery) during intervention (routine assessments, e.g. check-ups will be allowed)
  • Shift work with working during the night
  • Travelling more than 2 time zones in the last month before the observation or intervention periods or during the study
  • Persons who are pregnant or breastfeeding

Treatment and study plan

Profile-based behavioral sleep and stress management

Behavioral

After completion of the 5-week observational phase (phase A), the study team will conduct an interim analysis integrating WHOOP biometric data and SEMA3 self-reports on migraine, sleep, and stress. The aim is to identify individual sleep-stress patterns linked to migraine activity. Based on predefined criteria, participants will be assigned to one of four behavioral profiles: insomnia-like, sleep deprivation, social jetlag, or circadian misalignment. Mixed or unclassified cases will be grouped separately. All participants receive general behavioral recommendations on sleep hygiene, scheduling, and stress management. WHOOP-based personalized tips (e.g., optimal sleep windows, recovery days) will be encouraged. Profile-based participants also receive targeted prioritization of interventions most relevant to their sleep-migraine pattern, including techniques such as rhythm stabilization, relaxation training, or strategic light exposure.

Primary outcomes

  1. Decrease in the number of migraine days (6 weeks)

    Time frame: From phase A (baseline) to the end of phase B (6 weeks of intervention).

    The primary endpoint is the change in the number of migraine days per month from phase A (baseline) to the end of phase B, following 6 weeks of intervention. A reduction of 30% in self-reported monthly migraine days is defined as the primary outcome measure.

Secondary outcomes

  1. Association between total sleep time and migraine onset

    Time frame: Phase A (5 weeks).

    Correlation between objectively measured total sleep time (hours, derived from wearable device data) and the occurrence of migraine onset (yes/no), assessed using daily entries.

  2. Association between sleep latency and migraine onset

    Time frame: Phase A (5 weeks).

    Correlation between sleep latency (minutes, derived from wearable device data) and the occurrence of migraine onset (yes/no), assessed using daily entries.

  3. Association between sleep-wake time variability and migraine onset

    Time frame: Phase A (5 weeks).

    Correlation between variability in sleep-wake timing (derived descriptively from wearable device data) and the occurrence of migraine onset (yes/no), assessed using daily entries.

  4. Association between recovery score and migraine onset

    Time frame: Phase A (5 weeks).

    Correlation between recovery scores (as calculated by the wearable device application) and the occurrence of migraine onset (yes/no), assessed using daily entries.

  5. Association between perceived stress and migraine onset

    Time frame: Phase A (5 weeks).

    Correlation between perceived stress measured daily using the Stress Numeric Rating Scale-11 (Stress NRS-11) and the occurrence of migraine onset (yes/no).

  6. Difference in total sleep duration between nights with and without migraine attacks

    Time frame: Phase A (5 weeks)

    Mean difference in total sleep duration (hours), derived from wearable device data and daily entries, comparing nights with reported migraine attacks (yes) versus nights without migraine attacks (no), as recorded in the SEMA3 app.

  7. Difference in sleep quality between nights with and without migraine attacks

    Time frame: Phase A (5 weeks)

    Mean difference in subjective sleep quality, assessed via daily entries, comparing nights with reported migraine attacks (yes) versus nights without migraine attacks (no).

  8. Difference in light, deep, and REM-sleep proportion between nights with and without migraine attacks

    Time frame: Phase A (5 weeks)

    Mean difference in the proportion of time spent in light sleep, deep sleep, and REM-Sleep (% per night), derived from wearable device data, comparing nights with reported migraine attacks (yes) versus nights without migraine attacks (no).

  9. Change in subjective sleep quality from baseline to end of intervention

    Time frame: From phase A (baseline) to the end of phase B (intervention, 6 weeks).

    Mean change in subjective sleep quality measured using a validated questionnaire (Pittsburgh Sleep Quality Index, PSQI) and daily entries in the SEMA3 app, comparing the observational phase (Phase A, baseline) to the end of the intervention phase (Phase B).

  10. Change in total sleep duration from baseline to end of intervention

    Time frame: From phase A (baseline) to the end of phase B (intervention, 6 weeks).

    Mean change in total sleep duration (hours per night), derived from wearable device data, comparing the observational phase (Phase A, baseline) to the end of the intervention phase (Phase B).

  11. Change in sleep consistency score from baseline to end of intervention

    Time frame: From phase A (baseline) to the end of phase B (intervention, 6 weeks).

    Mean change in sleep consistency score, derived from wearable device data, comparing the observational phase (Phase A, baseline) to the end of the intervention phase (Phase B).

  12. Change in sleep onset variability from baseline to end of intervention

    Time frame: From phase A (baseline) to the end of phase B (intervention, 6 weeks).

    Mean change in variability of sleep onset timing, derived from wearable device data, comparing the observational phase (Phase A, baseline) to the end of the intervention phase (Phase B).

  13. Change in perceived stress from baseline to end of intervention

    Time frame: From phase A (baseline) to the end of phase B (intervention, 6 weeks).

    Mean change in perceived stress measured daily using the Stress Numeric Rating Scale-11 (0-10) via the SEMA3 app, comparing the observational phase (Phase A, baseline) to the end of the intervention phase (Phase B).

  14. Decrease in the number of migraine days (3 months)

    Time frame: From phase A (baseline) to the end of the study (3 months)

    Change in the number of migraine days per month from phase A (baseline) to the end of the study (3 months) (outcome measures: 30% reduction in the number of self-reported monthly migraine days before vs. after the intervention)

  15. Change in migraine severity from baseline to end of intervention

    Time frame: From phase A (baseline) to the end of phase B (intervention phase)

    Mean change in migraine severity, measured as average daily Numeric Rating Scale (NRS; 0-10) scores recorded in the SEMA3 app, comparing the observational phase (Phase A, baseline) to the end of the intervention phase (Phase B). Analysis includes only participants reporting migraine episodes in both phases.

  16. Change in migraine attack duration from baseline to end of intervention

    Time frame: From phase A (baseline) to the end of phase B (intervention phase)

    Mean change in migraine attack duration, measured as mean hours per episode based on participant self-report in the SEMA3 app, comparing the observational phase (Phase A, baseline) to the end of the intervention phase (Phase B). Analysis includes only participants reporting migraine episodes in both phases.

  17. Change in migraine severity from baseline to 3-month follow-up

    Time frame: From phase A (baseline) to 3-month follow-up

    Mean change in migraine severity, measured as average daily Numeric Rating Scale (NRS; 0-10) scores recorded in the SEMA3 app, comparing the observational phase (Phase A, baseline) to the end of the study (3-month follow-up). Analysis includes only participants reporting migraine episodes in both periods.

  18. Change in migraine attack duration from baseline to 3-month follow-up

    Time frame: From phase A (baseline) to 3-month follow-up

    Mean change in migraine attack duration, measured as mean hours per episode based on participant self-report in the SEMA3 app, comparing the observational phase (Phase A, baseline) to the end of the study (3-month follow-up). Analysis includes only participants reporting migraine episodes in both periods.

Other outcomes

  1. Identification of participant subgroups based on baseline sleep, stress, and migraine characteristics

    Time frame: Baseline (ende of Phase A)

    Identification of distinct participant subgroups using multivariate statistical techniques (e.g., cluster analysis, latent class modeling) based on baseline profiles including wearable-derived sleep metrics, daily perceived stress, and migraine frequency and severity.

  2. Association between baseline subgroup classification and intervention response

    Time frame: From phase A (baseline) to the end of the study (3-month follow-up).

    Association between participant subgroup membership (derived from baseline sleep, stress, and migraine profiles) and response to the behavioral intervention, defined as change in monthly migraine days and responder status (≥30% reduction).

  3. Sex and gender differences in sleep-stress-migraine associations

    Time frame: Phase A (5 weeks)

    To assess whether sex (biological) and gender (psychosocial) influence the association between sleep, circadian rhythm variables, perceived stress, and migraine burden (phase A).

    Sex will be recorded as a binary variable (male/female). Gender will be assess using The Stanford Gender-Related Variables for Health Research (GVHR), which reflects psychosocial gender traits (e.g., role orientation, identity, stress coping) and allows continuous, multidimensional assessment beyond binary sex.

    Outcome measures:

    • Subgroup comparisons of correlations between: wearable-derived sleep and recovery data (e.g. total sleep time, variability, heart rate variability (HRV)), daily perceived stress (Stress NRS-11), migraine symptoms (from SEMA3 data: frequency, intensity, NRS, duration in hours).
    • Moderation analyses using GVHR

    (Measurement tools: WHOOP biometric data, migraine symptom logs (SEMA3), GVHR, Stress NRS-11)

  4. Sex and gender differences in response to the personalized behavioral intervention

    Time frame: Pre-post comparison: phase A vs. phase B

    To evaluate whether sex and gender influence the effectiveness of the personalized behavioral intervention delivered in Phase B. Effectiveness is defined by change in migraine frequency, severity, and stress levels from Phase A to Phase B.

    Outcome measures:

    • Sex- and gender-based subgroup analyses of: change in monthly migraine days, change in the migraine severity (NRS) and duration (hours), and change in perceived stress (Stress NRS-11, PSS-10).
    • Interaction effects (sex x intervention; gender score (GVHR x intervention). (Measurement tools: WHOOP biometric data, migraine symptom logs (SEMA3), GVHR, Stress NRS-11, PSS-10)

  5. Adherence rate to behavioral intervention recommendations

    Time frame: Phase B (intervention phase) through 3-month follow-up

    Adherence to prescribed behavioral recommendations, measured as the percentage of completed adherence logs relative to expected entries over the intervention period.

  6. Participant-reported feasibility, usefulness, and perceived benefit of the intervention

    Time frame: End of Phase B (intervention phase) and 3-month follow-up

    Assessment of participant-reported feasibility, usefulness, and perceived benefit of the behavioral intervention, measured using a standardized user feedback questionnaire and summarized using descriptive statistics and thematic analysis of qualitative responses.

Study contacts

Contact information is provided by the study sponsor or research team.

Marie Therese Kleinsorge

CONTACT

[email protected]

+41 44 255 55 11

Susanne Wegener

CONTACT

[email protected]

+41 44 255 55 11

Sponsors and collaborators

Lead sponsor

Susanne Wegener

Other

Registry information

Official study title

Migraine Sleep Study (MiSleepS) - The Role of Sleep and Stress as a Trigger in Migraine

Acronym: MiSleepS

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
May 7, 2026
Registry last updated
May 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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