How Can we Treat Photophobia in Migraine

Study Overview
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Brief Summary
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Photophobia, the aberrantly increased sensitivity to light, is a common symptom in migraine patients and light discomfort is frequently found as a trigger for migraine attacks. In behavioral studies, planned exposure to light was found to reduce headache in migraineurs with photophobia, potentially by increasing habituation to this migraine trigger. Here, neurophysiological mechanisms of light exposure versus light deprivation therapy in migraine patients are investigated using functional magnetic resonance imaging (fMRI). Migraine patients and healthy controls receive light exposure therapy (Flash) and light deprivation therapy (Dark) for one hour daily on 7 consecutive days, in a crossover design with a wash-out period of three months. Study participants keep a diary including items on interictal and ictal photophobia, headache frequency and severity 7 days before, during, and 7 days after the interventions. One week before and one day after both interventions, fMRI using flickering light in a block design is applied. Functional activation is analyzed at whole-brain level and habituation of the visual cortex (V1) is modeled with the initial amplitude estimate and the corrected habituation slope.

Official Title
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How Can we Treat Photophobia in Migraine

Conditions
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Migraine Disorders, Photophobia

Intervention / Treatment
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* Behavioral: Light exposure (Flash)
* Behavioral: Light deprivation (Dark)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients: Migraine without aura according to the criteria of the International Classification of Headache Disorders (ICHD-3 beta) 1-4 days with migraine per month in the preceding last 3 months A score between 2 and 6 on a numeric rating scale for the intensity of interictal photophobia (range from 0 to 10 (= max. intensity)) A score >4 for ictal photophobia Controls No personal or family history of migraine A score <2 for photophobia Exclusion Criteria: Current or previous circadian rhythm disorders Current or previous major depression Current or previous anxiety disorders Current or previous medication overuse Besides migraine in the patient group, participants should not suffer from any other recurrent headache apart from infrequent tension-type headaches

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants receive light exposure therapy (Flash) and light deprivation therapy (Dark) for one hour daily on 7 consecutive days, in a crossover design with a wash-out period of 3 months. The sequence of the interventions is randomly allocated.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Flash first<br>Light exposure (Flash) first, light deprivation (Dark) second: Both interventions (Flash and Dark) are administered for one hour on 7 consecutive days. During the light exposure, participants are seated 120 cm in front of a white curtain that is illuminated by an LED light source. During the light deprivation, participants are seated in the same room used for light exposure, but in complete darkness. | Behavioral: Light exposure (Flash)<br>* Light exposure (Flash) is administered for one hour on 7 consecutive days. During the light exposure, participants are seated 120 cm in front of a white curtain that is illuminated by an LED light source (Dawe stroboscope type 1214B, 5 Hz).<br>Behavioral: Light deprivation (Dark)<br>* Light deprivation (Dark) is administered for one hour on 7 consecutive days. During the Dark intervention, participants are seated in a room in complete darkness.<br>|
| Experimental: Dark first<br>Light deprivation (Dark) first, Light exposure (Flash) second: Both interventions (Flash and Dark) are administered for one hour on 7 consecutive days. During the light exposure, participants are seated 120 cm in front of a white curtain that is illuminated by an LED light source. During the light deprivation, participants are seated in the same room used for light exposure, but in complete darkness. | Behavioral: Light exposure (Flash)<br>* Light exposure (Flash) is administered for one hour on 7 consecutive days. During the light exposure, participants are seated 120 cm in front of a white curtain that is illuminated by an LED light source (Dawe stroboscope type 1214B, 5 Hz).<br>Behavioral: Light deprivation (Dark)<br>* Light deprivation (Dark) is administered for one hour on 7 consecutive days. During the Dark intervention, participants are seated in a room in complete darkness.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline interictal photophobia during and after the interventions | Subjective sensitivity to light between migraine attacks is assessed using a numeric rating scale with the range from 0 (= no photophobia) to 10 (= max. photophobia). The numeric rating scale is daily completed by the participants over the study course using a structured diary. Daily reports are averaged for the duration of the baseline phase (7 days before the first intervention starts), for the duration of the interventions (Flash and Dark, 7 days each), and for 7 days after the interventions (Post Flash, Post Dark). | Change in interictal photophobia during the interventions (Flash and Dark, average over 7 days) and after the interventions (Post Flash, Post Dark, average over 7 days) relative to the baseline (average over 7 days before the first intervention starts). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline headache frequency during and after the interventions | In the structured diary, the participants report if a headache is present (1) or absent (0). Daily reports are averaged for the duration of the baseline phase (7 days before the first intervention starts), for the duration of the interventions (Flash and Dark, 7 days each), and for 7 days after the interventions (Post Flash, Post Dark). | Change in headache frequency during the interventions (Flash and Dark, average over 7 days) and after the interventions (Post Flash, Post Dark, average over 7 days) relative to the baseline (average over 7 days before the first intervention starts). | 
| Change from baseline headache severity during and after the interventions | If a headache is present that day, questions regarding headache severity (mild (1), moderate (2), severe (3)) are completed in the structured diary. Daily reports are averaged for the duration of the baseline phase (7 days before the first intervention starts), for the duration of the interventions (Flash and Dark, 7 days each), and for 7 days after the interventions (Post Flash, Post Dark). | Change in headache severity during the interventions (Flash and Dark, average over 7 days) and after the interventions (Post Flash, Post Dark, average over 7 days) relative to the baseline (average over 7 days before the first intervention starts). | 
| Change from baseline ictal photophobia during and after the interventions | If a headache is present that day, photophobia during the headache is assessed on a numeric rating scale with the range from 0 (= no photophobia) to 10 (= max. photophobia). Daily reports are averaged for the duration of the baseline phase (7 days before the first intervention starts), for the duration of the interventions (Flash and Dark, 7 days each), and for 7 days after the interventions (Post Flash, Post Dark). | Change in ictal photophobia during the interventions (Flash and Dark, average over 7 days) and after the interventions (Post Flash, Post Dark, average over 7 days) relative to the baseline (average over 7 days before the first intervention starts). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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migraine, photophobia, habituation, headache, functional magnetic resonance imaging