Trial Outcomes & Findings for Investigation and Modulation of the Mu-Opioid Mechanisms in Migraine (in Vivo) (NCT NCT02964741)

Last Updated: 2022-08-26

Results Overview

Moderate to severe headache is defined by the pain over 3 in an Numeric Rating Scale (NRS) ranging from 0 to 10 between end of treatment and one month follow-up.

Recruitment status

TERMINATED

Study phase

Target enrollment

44 participants

Primary outcome timeframe

End of treatment - over 1 month follow-up

Results posted on

2022-08-26

Participant Flow

Participant milestones

Participant milestones
Measure	Migraine Patients Active Group Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks). \Active Comparator Active Comparator: non-invasive brain stimulation (active protocol)	Migraine Patients Sham Group Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 10 days (M-F for 2 weeks). \Sham Comparator Sham Comparator: non-invasive brain stimulation (sham protocol)	Healthy Control Group Healthy Volunteers will be asked to undergo baseline assessments only (including imaging, but no brain stimulation). Healthy volunteer data (n \</= 10) may be used from a prior study (NINDS-K23062946 project \[IRBMED #HUM00027383; Dr. Alexandre DaSilva, Principal Investigator\]). Consent to use data for a future study was obtained in the informed consent document at the time of participation.
Overall Study STARTED	15	13	12
Overall Study COMPLETED	13	12	12
Overall Study NOT COMPLETED	2	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Migraine Patients Active Group Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks). \Active Comparator Active Comparator: non-invasive brain stimulation (active protocol)	Migraine Patients Sham Group Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 10 days (M-F for 2 weeks). \Sham Comparator Sham Comparator: non-invasive brain stimulation (sham protocol)
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	0	1
Overall Study claustrophobia	1	0

Baseline Characteristics

Investigation and Modulation of the Mu-Opioid Mechanisms in Migraine (in Vivo)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Migraine Patients Active Group n=13 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks). \Active Comparator Active Comparator: non-invasive brain stimulation (active protocol)	Migraine Patients Sham Group n=12 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 10 days (M-F for 2 weeks). \Sham Comparator Sham Comparator: non-invasive brain stimulation (sham protocol)	Healthy Control Group n=12 Participants Healthy Volunteers will be asked to undergo baseline assessments only (including imaging, but no brain stimulation). Healthy volunteer data (n \</= 10) may be used from a prior study (NINDS-K23062946 project \[IRBMED #HUM00027383; Dr. Alexandre DaSilva, Principal Investigator\]). Consent to use data for a future study was obtained in the informed consent document at the time of participation.	Total n=37 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	12 Participants n=7 Participants	12 Participants n=5 Participants	37 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	30.1 years STANDARD_DEVIATION 13.8 • n=5 Participants	30.3 years STANDARD_DEVIATION 8.8 • n=7 Participants	32.4 years STANDARD_DEVIATION 15.3 • n=5 Participants	30.9 years STANDARD_DEVIATION 12.6 • n=4 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	33 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	33 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	9 Participants n=7 Participants	7 Participants n=5 Participants	25 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment United States	13 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants	37 participants n=4 Participants

PRIMARY outcome

Timeframe: End of treatment - over 1 month follow-up

Moderate to severe headache is defined by the pain over 3 in an Numeric Rating Scale (NRS) ranging from 0 to 10 between end of treatment and one month follow-up.

Outcome measures

Outcome measures
Measure	Migraine Patients Active Group n=13 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks). \Active Comparator Active Comparator: non-invasive brain stimulation (active protocol)	Migraine Patients Sham Group n=12 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 10 days (M-F for 2 weeks). \Sham Comparator Sham Comparator: non-invasive brain stimulation (sham protocol)
Days With Moderate-to-severe Headache	2.9 days Interval 2.1 to 3.9	3.3 days Interval 2.4 to 4.4

PRIMARY outcome

Timeframe: End of treatment - over 1 month follow-up

Number of participants who showed a 50% reduction of days with moderate-to-severe headache compared to baseline.

Outcome measures

Outcome measures
Measure	Migraine Patients Active Group n=13 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks). \Active Comparator Active Comparator: non-invasive brain stimulation (active protocol)	Migraine Patients Sham Group n=12 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 10 days (M-F for 2 weeks). \Sham Comparator Sham Comparator: non-invasive brain stimulation (sham protocol)
Responder Rate	10 participants	6 participants

SECONDARY outcome

Timeframe: Approximately 45 days (Screening Visit [Original Baseline] to Follow Up #2 [28-days post-HD-tDCS treatment])

Visual Analog Scale measures pain on a 0 to 10 scale, where 0 is "no pain" and 10 is "worst possible pain"

Outcome measures

Outcome measures
Measure	Migraine Patients Active Group n=13 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks). \Active Comparator Active Comparator: non-invasive brain stimulation (active protocol)	Migraine Patients Sham Group n=12 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 10 days (M-F for 2 weeks). \Sham Comparator Sham Comparator: non-invasive brain stimulation (sham protocol)
Change in Pain Intensity Level Measured by the Visual Analog Scale in Migraineurs (Active or Sham)	-4.1 score on scale Interval -5.3 to -2.8	-4.4 score on scale Interval -5.7 to -3.1

SECONDARY outcome

Timeframe: End of treatment - over 1 month follow-up

Percentage of participants having moderate-to-severe headache between end of treatment and one month follow-up. Defined as a response greater than 3 on the (0-10) NRS scale

Outcome measures

Outcome measures
Measure	Migraine Patients Active Group n=13 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks). \Active Comparator Active Comparator: non-invasive brain stimulation (active protocol)	Migraine Patients Sham Group n=12 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 10 days (M-F for 2 weeks). \Sham Comparator Sham Comparator: non-invasive brain stimulation (sham protocol)
Moderate to Severe Headache	61.5 percentage of participants Interval 35.1 to 88.0	66.7 percentage of participants Interval 40.0 to 93.3

SECONDARY outcome

Timeframe: End of treatment - over 1 month follow-up

Percentage of participants who used rescue medication between end of treatment and one month follow-up

Outcome measures

Outcome measures
Measure	Migraine Patients Active Group n=13 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks). \Active Comparator Active Comparator: non-invasive brain stimulation (active protocol)	Migraine Patients Sham Group n=12 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 10 days (M-F for 2 weeks). \Sham Comparator Sham Comparator: non-invasive brain stimulation (sham protocol)
Use of Rescue Medication	38.5 percentage of participants Interval 12.0 to 64.9	66.7 percentage of participants Interval 40.0 to 93.3

SECONDARY outcome

Timeframe: Time between PET #1 and PET #2 is typically 21 days (minimum 17 days; maximum 42 days).

Mu-opioid receptor BPND at PET #2 will be subtracted from mu-opioid receptor BPND at PET #1. PET #1 occurs during the week before HD-tDCS treatment begins. PET #2 occurs during the week after the final HD-tDCS treatment is completed.

Outcome measures

Outcome measures
Measure	Migraine Patients Active Group n=13 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks). \Active Comparator Active Comparator: non-invasive brain stimulation (active protocol)	Migraine Patients Sham Group n=11 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 10 days (M-F for 2 weeks). \Sham Comparator Sham Comparator: non-invasive brain stimulation (sham protocol)
Change in Mu-opioid Receptor Non-displaceable Binding Potential (BPND) in the Brains of Migraineurs During Sustained Thermal Pain Threshold Stress Challenge Subsequent to Treatment by HD-tDCS (Active or Sham).	0.15 non-displaceable binding potential Standard Deviation 0.09	-0.10 non-displaceable binding potential Standard Deviation 0.11

SECONDARY outcome

Timeframe: Time between PET #1 and PET #2 is typically 21 days (minimum 17 days; maximum 42 days).

Outcome measures

Outcome measures
Measure	Migraine Patients Active Group n=13 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks). \Active Comparator Active Comparator: non-invasive brain stimulation (active protocol)	Migraine Patients Sham Group n=11 Participants Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 10 days (M-F for 2 weeks). \Sham Comparator Sham Comparator: non-invasive brain stimulation (sham protocol)
Change in Mu-opioid Receptor Non-displaceable Binding Potential (BPND) in the Brains of Migraineurs at Rest Subsequent to Treatment by HD-tDCS (Active or Sham).	0.07 non-displaceable binding potential Standard Deviation 0.13	-0.15 non-displaceable binding potential Standard Deviation 0.13

Adverse Events

Migraine Patients Active Group

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Migraine Patients Sham Group

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Migraine Patients Active Group n=13 participants at risk Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 20 minute sessions, once daily for 10 days (M-F for 2 weeks). \Active Comparator Active Comparator: non-invasive brain stimulation (active protocol)	Migraine Patients Sham Group n=12 participants at risk Episodic migraine patients will be randomized (Taves method) to receive high-definition transcranial direct current stimulation (HD-tDCS\) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 10 days (M-F for 2 weeks). \Sham Comparator Sham Comparator: non-invasive brain stimulation (sham protocol)
Investigations Headache	46.2% 6/13 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.	33.3% 4/12 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.
Investigations Neck pain	46.2% 6/13 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.	25.0% 3/12 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.
Investigations scalp pain	30.8% 4/13 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.	33.3% 4/12 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.
Investigations scalp burns	15.4% 2/13 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.	33.3% 4/12 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.
Investigations tingling	53.8% 7/13 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.	91.7% 11/12 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.
Investigations skin redness	7.7% 1/13 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.	8.3% 1/12 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.
Investigations sleepiness	61.5% 8/13 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.	66.7% 8/12 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.
Investigations trouble concentrating	15.4% 2/13 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.	33.3% 4/12 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.
Investigations other (mild forms of dizziness, scalp tenderness, mild itching, etc)	38.5% 5/13 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.	8.3% 1/12 • During the 2-weeks of HD-tDCS treatment Adverse Events were collected using a questionnaire that reflects common side effects of tDCS treatment. The questionnaire was administered before and after each of 10 tDCS treatment sessions. All of the adverse events reported were expected and mild in severity.

Additional Information

Jacqueline Dobson

University of Michigan

Phone: 734-763-8469

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place