Migraine
Conditions
Brief summary
Cranial electrotherapy stimulation (CES) may be a safe adjunct to medical treatment for pain relief in migraine patients. However, despite the number of CES studies done, many have been open label, single blinded, or have utilized a small group of patients.
Detailed description
This study will evaluate the efficacy of the Fisher Wallace Cranial Stimulator in persons with chronic migraine who have not achieved satisfactory pain control on their current medications.
Interventions
DEVICECranial Electrostimulator
participant wears active cranial electrostimulation device for 20 minutes daily for 28 days
DEVICESham Device
participant wears sham device for 20 minutes daily for 28 days
Sponsors
University of Toledo Health Science Campus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subjects satisfying the IHS (International Headache Society) criteria for migraine * Subjects have not achieved satisfactory pain control on their current medication * Ability to maintain a daily headache diary * Stable medication use related to migraine for at least 4 weeks prior to enrollment in the study
Exclusion criteria
* Previous exposure to or experience with cranial electrotherapy stimulation (CES) * Contraindications to Fisher Wallace stimulator, such as cardiac pacemakers or implantable defibrillators, known or suspected heart disease, or pregnancy * Seizure disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Headache Days | 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). |
| Depression Score (PATIENT HEALTH QUESTIONNAIRE [PHQ] 9) | 14 days recall; measured at end of run-in month and blinded month | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Headache Impact Test-6 | 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. |
| Headache Impact Test (HIT-6) (Measure of Disability Due to Headaches) | 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. |
| Generalized Anxiety Disorder Score (GAD 7) | 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 |
| Headache Days | 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). |
| Somatic Symptom Score (Patient Health Questionnaire-15) | 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. |
| Epworth Sleepiness Scale Score | 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. |
| Somatic Symptom Severity (Patient Health Questionnaire 15) | 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 |
| Depression Score (Patient Health Questionnaire-9) | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment dates: Dec 2010 - Jan 2013 Recruitment status: Not enrolling. Location: Neurology Clinic
Pre-assignment details
Enrolled participants were randomized to receive verum or sham intervention. Completion of one (run-in) month headache diary was required before obtaining device.
Participants by arm
| Arm | Count |
|---|---|
| Verum Verum : wears active Electrostimulator device daily for 20 minutes for 28 days | 24 |
| Sham Sham Device : wears Sham device daily for 20 minutes for 28 days | 27 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Blinded Month | Adverse Event | 2 | 0 |
| Blinded Month | Diary data incomplete | 0 | 1 |
| Blinded Month | Lack of Efficacy | 5 | 0 |
| Blinded Month | Lost to Follow-up | 1 | 0 |
| Blinded Month | Protocol Violation | 2 | 1 |
| Open Label Month | Lost to Follow-up | 0 | 1 |
| Run-in Month | 1st seizure during run-in month | 0 | 1 |
| Run-in Month | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | Sham | Verum | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 24 Participants | 51 Participants |
| Age, Continuous | 43.59 years STANDARD_DEVIATION 10.25 | 42.67 years STANDARD_DEVIATION 12.33 | 43.14 years STANDARD_DEVIATION 11.17 |
| Region of Enrollment United States | 27 participants | 24 participants | 51 participants |
| Sex: Female, Male Female | 24 Participants | 19 Participants | 43 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 34 | 0 / 34 |
| serious Total, serious adverse events | 0 / 34 | 0 / 34 |
Outcome results
Primary
Depression Score (PATIENT HEALTH QUESTIONNAIRE [PHQ] 9)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Depression Score (PATIENT HEALTH QUESTIONNAIRE [PHQ] 9) | 0 depression score/14 day recall |
| Sham | Depression Score (PATIENT HEALTH QUESTIONNAIRE [PHQ] 9) | 0.30 depression score/14 day recall |
Comparison: The a priori alpha level was set at p \< 0.05, and beta 0.2. Assuming that 20% of persons with the sham device and 60% of persons with CES device will meet the primary end point of ≥50% decrease in the frequency of headache days over the course of the study, 27 subjects are enrolled per group. The null hypothesis: No difference in the depression score/14 day recall between the two groups.p-value: 0.98Wilcoxon (Mann-Whitney)
Primary
Mean Headache Days
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).
Time frame: 28 day period during run-in month and blinded month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Mean Headache Days | 0.88 headache days/ 28 day period |
| Sham | Mean Headache Days | -0.52 headache days/ 28 day period |
Comparison: The a priori alpha level was set at p \< 0.05, and a power of 0.80 (80%) was used to compute the number of subjects needed to find a meaningful difference between the verum and sham groups. Assuming that 20% of persons with the sham device and 60% of persons with CES device will meet the primary end point of ≥50% decrease in the frequency of headache days over the course of the study, 27 subjects are enrolled per group.p-value: 0.3Wilcoxon (Mann-Whitney)
Secondary
Depression Score (Patient Health Questionnaire-9)
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.
Time frame: 14 day recall, recorded at the end of run-in and open label months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Depression Score (Patient Health Questionnaire-9) | 1.58 score on a scale |
| Sham | Depression Score (Patient Health Questionnaire-9) | 0.62 score on a scale |
p-value: 0.3Wilcoxon (Mann-Whitney)
Secondary
Epworth Sleepiness Scale Score
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.
Time frame: Score recorded at the end of run-in and open label month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Epworth Sleepiness Scale Score | 0.50 score on a scale |
| Sham | Epworth Sleepiness Scale Score | 0.35 score on a scale |
p-value: 0.92Wilcoxon (Mann-Whitney)
Secondary
Epworth Sleepiness Scale Score
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.
Time frame: recorded at the end of run-in month and blinded month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Epworth Sleepiness Scale Score | 0.84 score on a scale |
| Sham | Epworth Sleepiness Scale Score | 1.00 score on a scale |
p-value: 0.83Wilcoxon (Mann-Whitney)
Secondary
Generalized Anxiety Disorder Score (GAD 7)
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
Time frame: 14 day recall, recorded at the end of run-in and open label months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Generalized Anxiety Disorder Score (GAD 7) | 1.13 score on a scale |
| Sham | Generalized Anxiety Disorder Score (GAD 7) | 1.27 score on a scale |
p-value: 0.98Wilcoxon (Mann-Whitney)
Secondary
Generalized Anxiety Disorder Score (GAD 7)
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
Time frame: 14 days recall; measured at end of run-in month and blinded month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Generalized Anxiety Disorder Score (GAD 7) | -0.33 score on a scale |
| Sham | Generalized Anxiety Disorder Score (GAD 7) | 2.41 score on a scale |
p-value: 0.02Wilcoxon (Mann-Whitney)
Secondary
Headache Days
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).
Time frame: 28 day period in run-in month and open label month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Headache Days | 0.67 headache days/ 28 day period |
| Sham | Headache Days | 0.76 headache days/ 28 day period |
p-value: 0.89Wilcoxon (Mann-Whitney)
Secondary
Headache Impact Test-6
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.
Time frame: after run-in month, after blinded month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Headache Impact Test-6 | 2.13 score on a scale |
| Sham | Headache Impact Test-6 | 1.22 score on a scale |
p-value: 0.75Wilcoxon (Mann-Whitney)
Secondary
Headache Impact Test (HIT-6) (Measure of Disability Due to Headaches)
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.
Time frame: 28 day period in run-in month and open label month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Headache Impact Test (HIT-6) (Measure of Disability Due to Headaches) | 3.25 score on a scale |
| Sham | Headache Impact Test (HIT-6) (Measure of Disability Due to Headaches) | 2.65 score on a scale |
p-value: 0.73Wilcoxon (Mann-Whitney)
Secondary
Somatic Symptom Score (Patient Health Questionnaire-15)
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.
Time frame: 28 day period in run-in month and open label month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Somatic Symptom Score (Patient Health Questionnaire-15) | 0.84 score on a scale |
| Sham | Somatic Symptom Score (Patient Health Questionnaire-15) | 1.00 score on a scale |
p-value: 0.87Wilcoxon (Mann-Whitney)
Secondary
Somatic Symptom Severity (Patient Health Questionnaire 15)
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
Time frame: 28 days recall; measured at end of run-in month and blinded month
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Verum | Somatic Symptom Severity (Patient Health Questionnaire 15) | 0.38 score on a scale |
| Sham | Somatic Symptom Severity (Patient Health Questionnaire 15) | 0.33 score on a scale |
p-value: 0.97Wilcoxon (Mann-Whitney)