How Can we Treat Photophobia in Migraine

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.

Study Overview

• Status: Completed
• Conditions: Migraine Disorders; Photophobia
• Intervention / Treatment: Behavioral: Light exposure (Flash); Behavioral: Light deprivation (Dark)

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Flash first; 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); 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).; Behavioral: Light deprivation (Dark); 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.
Experimental: Dark first; 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); 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).; Behavioral: Light deprivation (Dark); 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.

What is the study measuring?

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).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline functional activation in the primary visual cortex after the interventions	3 Tesla functional Magnetic Resonance Imaging (fMRI) is used to analyze brain activation induced by flickering light (10 functional runs, block design with 7 alternating blocks (20 s each) of flashing light (8 Hz) and darkness (140 s per run)).	fMRI one day after the completion of each intervention (Flash, Dark) is compared the the baseline fMRI measured 7 days before the first intervention starts.

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Collaborators: Austrian Science Fund (FWF)
• Investigators: Principal Investigator: Roland Beisteiner, MD, Department of Neurology, Medical University of Vienna

Publications and helpful links

General Publications

• Matt E, Aslan T, Amini A, Sariçiçek K, Seidel S, Martin P, Wöber C, Beisteiner R. Avoid or seek light - a randomized crossover fMRI study investigating opposing treatment strategies for photophobia in migraine. J Headache Pain. 2022 Aug 11;23(1):99. doi: 10.1186/s10194-022-01466-0.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): September 30, 2019

Study Registration Dates

• First Submitted: May 2, 2022
• First Submitted That Met QC Criteria: May 6, 2022
• First Posted (Actual): May 11, 2022

Study Record Updates

• Last Update Posted (Actual): May 11, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: functional magnetic resonance imaging; headache; migraine; photophobia; habituation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Sensation Disorders; Headache Disorders, Primary; Headache Disorders; Vision Disorders; Migraine Disorders; Photophobia
• Other Study ID Numbers: KLI 455

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No