Sleep, Stress and Migraine - an Observational and Training Study (MiSleepS)
Migraine Sleep Study (MiSleepS) - The Role of Sleep and Stress as a Trigger in Migraine
연구 개요
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: Susanne Wegener
- 전화번호: +41 44 255 55 11
- 이메일: susanne.wegener@usz.ch
연구 연락처 백업
- 이름: Marie Therese Kleinsorge
- 전화번호: +41 44 255 55 11
- 이메일: marie.kleinsorge@usz.ch
연구 장소
-
-
-
Zurich, 스위스, 8091
- 모병
- University Hospital Zurich, Department of Neurology
-
연락하다:
- Susanne Wegener
- 전화번호: +41 44 255 55 11
- 이메일: susanne.wegener@usz.ch
-
연락하다:
- Marie Therese Kleinsorge
- 전화번호: +41 44 255 55 11
- 이메일: marie.kleinsorge@usz.ch
-
-
참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 다른
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Personalized Behavioral Intervention Arm
N=70 participants undergo a 5-week observational phase (phase A) with continuous wearable tracking and daily app-based self-reporting. After an interim analysis, they are assigned to a sleep/stress-related behavioral profiles. In the following 6-week intervention phase (phase B), they receive personalized behavioral recommendations tailored to their profile and implement them with ongoing digital monitoring. The first 10 participants (run-in group) follow the same protocol but do not receive personalized interventions in phase B. This group serves as a control to distinguish behavioral effects of the intervention from those caused by increased self-monitoring or study participation alone (Hawthorne effect). |
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.
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Decrease in the number of migraine days (6 weeks)
기간: 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.
|
From phase A (baseline) to the end of phase B (6 weeks of intervention).
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Association between total sleep time and migraine onset
기간: 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.
|
Phase A (5 weeks).
|
|
Association between sleep latency and migraine onset
기간: 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.
|
Phase A (5 weeks).
|
|
Association between sleep-wake time variability and migraine onset
기간: 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.
|
Phase A (5 weeks).
|
|
Association between recovery score and migraine onset
기간: 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.
|
Phase A (5 weeks).
|
|
Association between perceived stress and migraine onset
기간: 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).
|
Phase A (5 weeks).
|
|
Difference in total sleep duration between nights with and without migraine attacks
기간: 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.
|
Phase A (5 weeks)
|
|
Difference in sleep quality between nights with and without migraine attacks
기간: 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).
|
Phase A (5 weeks)
|
|
Difference in light, deep, and REM-sleep proportion between nights with and without migraine attacks
기간: 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).
|
Phase A (5 weeks)
|
|
Change in subjective sleep quality from baseline to end of intervention
기간: 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).
|
From phase A (baseline) to the end of phase B (intervention, 6 weeks).
|
|
Change in total sleep duration from baseline to end of intervention
기간: 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).
|
From phase A (baseline) to the end of phase B (intervention, 6 weeks).
|
|
Change in sleep consistency score from baseline to end of intervention
기간: 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).
|
From phase A (baseline) to the end of phase B (intervention, 6 weeks).
|
|
Change in sleep onset variability from baseline to end of intervention
기간: 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).
|
From phase A (baseline) to the end of phase B (intervention, 6 weeks).
|
|
Change in perceived stress from baseline to end of intervention
기간: 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).
|
From phase A (baseline) to the end of phase B (intervention, 6 weeks).
|
|
Decrease in the number of migraine days (3 months)
기간: 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)
|
From phase A (baseline) to the end of the study (3 months)
|
|
Change in migraine severity from baseline to end of intervention
기간: 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.
|
From phase A (baseline) to the end of phase B (intervention phase)
|
|
Change in migraine attack duration from baseline to end of intervention
기간: 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.
|
From phase A (baseline) to the end of phase B (intervention phase)
|
|
Change in migraine severity from baseline to 3-month follow-up
기간: 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.
|
From phase A (baseline) to 3-month follow-up
|
|
Change in migraine attack duration from baseline to 3-month follow-up
기간: 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.
|
From phase A (baseline) to 3-month follow-up
|
기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Identification of participant subgroups based on baseline sleep, stress, and migraine characteristics
기간: 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.
|
Baseline (ende of Phase A)
|
|
Association between baseline subgroup classification and intervention response
기간: 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).
|
From phase A (baseline) to the end of the study (3-month follow-up).
|
|
Sex and gender differences in sleep-stress-migraine associations
기간: 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:
(Measurement tools: WHOOP biometric data, migraine symptom logs (SEMA3), GVHR, Stress NRS-11) |
Phase A (5 weeks)
|
|
Sex and gender differences in response to the personalized behavioral intervention
기간: 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:
|
Pre-post comparison: phase A vs. phase B
|
|
Adherence rate to behavioral intervention recommendations
기간: 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.
|
Phase B (intervention phase) through 3-month follow-up
|
|
Participant-reported feasibility, usefulness, and perceived benefit of the intervention
기간: 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.
|
End of Phase B (intervention phase) and 3-month follow-up
|
공동 작업자 및 조사자
스폰서
수사관
- 수석 연구원: Susanne Wegener, University Hospital Zurich, Department of Neurology
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 2025-01186
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .