Trial Outcomes & Findings for Cranial Electrotherapy Stimulation in the Treatment of Migraine Headaches (NCT NCT01265797)

NCT ID: NCT01265797

Last Updated: 2015-02-10

Results Overview

Mean change in headache days between 28 day run-in month and 28 day blinded month, i.e. run-in month mean minus blinded month mean. A good response is \>= 50% reduction in headache days (congruent with the Guidelines for Trial of Behavioral Treatments for Recurrent Headache).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 68 participants
• Primary outcome timeframe: 28 day period during run-in month and blinded month
• Results posted on: 2015-02-10

Participant Flow

Recruitment dates: Dec 2010 - Jan 2013 Recruitment status: Not enrolling. Location: Neurology Clinic

Enrolled participants were randomized to receive verum or sham intervention. Completion of one (run-in) month headache diary was required before obtaining device.

Participant milestones

Measure	Verum Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Run-in Month STARTED	34	34
Run-in Month COMPLETED	34	29
Run-in Month NOT COMPLETED	0	5
Blinded Month STARTED	34	29
Blinded Month COMPLETED	24	27
Blinded Month NOT COMPLETED	10	2
Open Label Month STARTED	24	27
Open Label Month COMPLETED	24	26
Open Label Month NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Verum Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Run-in Month Withdrawal by Subject	0	4
Run-in Month 1st seizure during run-in month	0	1
Blinded Month Lack of Efficacy	5	0
Blinded Month Lost to Follow-up	1	0
Blinded Month Protocol Violation	2	1
Blinded Month Adverse Event	2	0
Blinded Month Diary data incomplete	0	1
Open Label Month Lost to Follow-up	0	1

Baseline Characteristics

Cranial Electrotherapy Stimulation in the Treatment of Migraine Headaches

Baseline characteristics by cohort

Measure	Verum n=24 Participants Verum : wears active Electrostimulator device daily for 20 minutes for 28 days	Sham n=27 Participants Sham Device : wears Sham device daily for 20 minutes for 28 days	Total n=51 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=93 Participants	27 Participants n=4 Participants	51 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	42.67 years STANDARD_DEVIATION 12.33 • n=93 Participants	43.59 years STANDARD_DEVIATION 10.25 • n=4 Participants	43.14 years STANDARD_DEVIATION 11.17 • n=27 Participants
Sex: Female, Male Female	19 Participants n=93 Participants	24 Participants n=4 Participants	43 Participants n=27 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	3 Participants n=4 Participants	8 Participants n=27 Participants
Region of Enrollment United States	24 participants n=93 Participants	27 participants n=4 Participants	51 participants n=27 Participants

PRIMARY outcome

Timeframe: 28 day period during run-in month and blinded month

Mean change in headache days between 28 day run-in month and 28 day blinded month, i.e. run-in month mean minus blinded month mean. A good response is >= 50% reduction in headache days (congruent with the Guidelines for Trial of Behavioral Treatments for Recurrent Headache).

Outcome measures

Measure	Verum n=24 Participants Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham n=27 Participants Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Mean Headache Days	0.88 headache days/ 28 day period Interval -0.38 to 2.13	-0.52 headache days/ 28 day period Interval -2.49 to 1.45

PRIMARY outcome

Timeframe: 14 days recall; measured at end of run-in month and blinded month

Population: The number of participants included the individuals who have completed the run-in period and the blinded period. The data was analyzed 'per protocol' based on the number of participants completing the blinded period.

Mean difference of PHQ-9 score between the run-in month and blinded month, i.e. PHQ-9 score from run-in month minus blinded month. The PHQ-9 is a tool for assisting in diagnosing depression (over the prior 2 week period) as well as selecting and monitoring treatment. There are nine items, with responses each ranging from 0 (not at all) to 3 (nearly every day), for a total range of 0 to 27. The higher the total the more severe the depressive symptoms.

Outcome measures

Measure	Verum n=24 Participants Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham n=27 Participants Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Depression Score (PATIENT HEALTH QUESTIONNAIRE [PHQ] 9)	0 depression score/14 day recall Interval -1.37 to 1.37	0.30 depression score/14 day recall Interval -0.89 to 1.49

SECONDARY outcome

Timeframe: 28 day period in run-in month and open label month

Mean change in headache days between 28 day run-in month and 28 day open label month, i.e. run-in month mean minus open label month mean. A good response is >= 50% reduction in headache days (congruent with the Guidelines for Trial of Behavioral Treatments for Recurrent Headache).

Outcome measures

Measure	Verum n=24 Participants Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham n=26 Participants Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Headache Days	0.67 headache days/ 28 day period Interval -0.63 to 1.96	0.76 headache days/ 28 day period Interval -1.77 to 3.22

SECONDARY outcome

Timeframe: 14 day recall, recorded at the end of run-in and open label months

Mean difference of PHQ-9 score between the run-in month and open label month, i.e. PHQ-9 score from run-in month minus open label month. The PHQ-9 is a tool for assisting in diagnosing depression (over the prior 2 week period) as well as selecting and monitoring treatment. There are nine items, with responses each ranging from 0 (not at all) to 3 (nearly every day), for a total range of 0 to 27. The higher the total the more severe the depressive symptoms.

Outcome measures

Measure	Verum n=24 Participants Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham n=26 Participants Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Depression Score (Patient Health Questionnaire-9)	1.58 score on a scale Interval 0.04 to 3.12	0.62 score on a scale Interval -0.91 to 2.14

SECONDARY outcome

Timeframe: after run-in month, after blinded month

Mean difference in HIT-6 score between run-in month and blinded month. The HIT-6 is a tool for screening and monitoring change in headache disability. This disease-specific health survey is intended for adults 18 years of age and older, and is available with a standard four-week recall period. It is a 6 item questionnaire with scores for each item ranging from 6 (never) to 13 (always). The minimum overall score is 36 and the maximum is 78. Higher scores represent greater disability.

Outcome measures

Measure	Verum n=24 Participants Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham n=27 Participants Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Headache Impact Test-6	2.13 score on a scale Interval 0.15 to 4.1	1.22 score on a scale Interval -0.19 to 2.64

SECONDARY outcome

Timeframe: 28 day period in run-in month and open label month

Mean difference in HIT-6 score between run-in month and open label month. The HIT-6 is a tool for screening and monitoring change in headache disability. This disease-specific health survey is intended for adults 18 years of age and older, and is available with a standard four-week recall period. It is a 6 item questionnaire with scores for each item ranging from 6 (never) to 13 (always). The minimum overall score is 36 and the maximum is 78. Higher scores represent greater disability.

Outcome measures

Measure	Verum n=24 Participants Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham n=26 Participants Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Headache Impact Test (HIT-6) (Measure of Disability Due to Headaches)	3.25 score on a scale Interval 1.39 to 5.1	2.65 score on a scale Interval 0.07 to 5.23

SECONDARY outcome

Timeframe: 14 days recall; measured at end of run-in month and blinded month

Mean difference in GAD 7 score between run-in month and blinded month. This is a screening tool and severity measure for generalized anxiety disorder addressing symptoms over the prior 2 weeks. It is a 7 item questionnaire with response scores for each item ranging from 0 (not at all) to 3 (every day). The range for the total score is 0 to 21, with higher scores representing greater symptoms of anxiety

Outcome measures

Measure	Verum n=24 Participants Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham n=27 Participants Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Generalized Anxiety Disorder Score (GAD 7)	-0.33 score on a scale Interval -1.42 to 0.76	2.41 score on a scale Interval 0.51 to 4.3

SECONDARY outcome

Timeframe: 14 day recall, recorded at the end of run-in and open label months

Mean difference in GAD 7 score between run-in month and open label month. This is a screening tool and severity measure for generalized anxiety disorder addressing symptoms over the prior 2 weeks. It is a 7 item questionnaire with response scores for each item ranging from 0 (not at all) to 3 (every day). The range for the total score is 0 to 21, with higher scores representing greater symptoms of anxiety

Outcome measures

Measure	Verum n=24 Participants Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham n=26 Participants Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Generalized Anxiety Disorder Score (GAD 7)	1.13 score on a scale Interval 0.03 to 2.22	1.27 score on a scale Interval -0.35 to 2.88

SECONDARY outcome

Timeframe: 28 days recall; measured at end of run-in month and blinded month

Mean difference in PHQ 15 score between run-in month and blinded month. The PHQ-15 comprises 15 somatic symptoms experienced over the prior 4 weeks and their severity, each symptom scored from 0 ("not bothered at all") to 2 ("bothered a lot"). The range for the overall score is between 0 and 30, with higher score representing more severe somatic symptoms

Outcome measures

Measure	Verum n=24 Participants Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham n=27 Participants Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Somatic Symptom Severity (Patient Health Questionnaire 15)	0.38 score on a scale Interval -1.29 to 2.04	0.33 score on a scale Interval -0.68 to 1.34

SECONDARY outcome

Timeframe: 28 day period in run-in month and open label month

Mean difference in PHQ 15 score between run-in month and open label month. The PHQ-15 comprises 15 somatic symptoms experienced over the prior 4 weeks and their severity, each symptom scored from 0 ("not bothered at all") to 2 ("bothered a lot"). The range for the overall score is between 0 and 30, with higher score representing more severe somatic symptoms.

Outcome measures

Measure	Verum n=24 Participants Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham n=26 Participants Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Somatic Symptom Score (Patient Health Questionnaire-15)	0.84 score on a scale Interval -0.4 to 2.06	1.00 score on a scale Interval -0.17 to 2.28

SECONDARY outcome

Timeframe: recorded at the end of run-in month and blinded month

Mean difference of Epworth Sleepiness Scale score between run-in month and blinded month. The Epworth Sleepiness Scale is used to measure excessive daytime sleepiness. This is an 8 item questionnaire, recalling probability of falling asleep in "recent times". The subjects are asked to rate probability of falling asleep in eight different situations. The score for each item ranges from 0 (would never doze) to 3 (high chance of dozing), with the overall score range of 0 to 24. Higher scores represent higher probability of falling asleep.

Outcome measures

Measure	Verum n=24 Participants Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham n=27 Participants Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Epworth Sleepiness Scale Score	0.84 score on a scale Interval 0.4 to 2.06	1.00 score on a scale Interval 0.17 to 2.28

SECONDARY outcome

Timeframe: Score recorded at the end of run-in and open label month

Mean difference of Epworth Sleepiness Scale score between run-in month and open label month. The Epworth Sleepiness Scale is used to measure excessive daytime sleepiness. This is an 8 item questionnaire, recalling probability of falling asleep in "recent times". The subjects are asked to rate probability of falling asleep in eight different situations. The score for each item ranges from 0 (would never doze) to 3 (high chance of dozing), with the overall score range of 0 to 24. Higher scores represent higher probability of falling asleep.

Outcome measures

Measure	Verum n=24 Participants Verum : wears active cranial electrostimulation device for 20 minutes daily for 28 days	Sham n=26 Participants Sham: wears sham cranial electrostimulation device for 20 minutes daily for 28 days
Epworth Sleepiness Scale Score	0.50 score on a scale Interval -0.85 to 1.85	0.35 score on a scale Interval -0.59 to 1.28

Adverse Events

Verum

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Sham

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Verum n=34 participants at risk Verum : wears active cranial electrostimulation (CES) device for 20 minutes daily for 28 days	Sham n=34 participants at risk Sham: wears sham cranial electrostimulation (CES) device for 20 minutes daily for 28 days
Eye disorders Visual Flickering	17.6% 6/34 • Number of events 6 • Over the 28 day blinded period, and 28 day open label period for those wishing to continue after completion of the study (total of 8 weeks) Inquiry regarding adverse events was made at the visits following the blinded and open label period. We also recorded adverse events reported during phone calls with participants during the blinded and open label period.	0.00% 0/34 • Over the 28 day blinded period, and 28 day open label period for those wishing to continue after completion of the study (total of 8 weeks) Inquiry regarding adverse events was made at the visits following the blinded and open label period. We also recorded adverse events reported during phone calls with participants during the blinded and open label period.

Additional Information

Gretchen Tietjen, MD

University of Toledo

Phone: 419-383-3544

Email: gretchen.tietjen@utoledo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place