MigraineNCT05161871
Transcranial Direct Current Stimulation Plus Monoclonal Antibodies Acting on the CGRP Pathway for Migraine
A study testing Cathodal transcranial direct current stimulation in people with Migraine, run by University of L'Aquila at 1 site in Italy.
Trial summary
Electrophysiological changes that occur in the brains of migraine patients, lead to the activation of nociceptive centers, including a peripheral neural structure, the trigeminal ganglion (TG), which releases pain-inducing peptides and mostly calcitonin gene-related peptide (CGRP). Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Migraine
- What is being tested?
- Cathodal transcranial direct current stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 16 May 2022to 16 Apr 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- male or female patients, aged between 40 and 70 years, referring to the Headache Center of the University of L'Aquila;
- a diagnosis of migraine with or without aura according to the International Classification of Headache Disorders, 3rd Edition (ICHD-3; https://ichd-3.org/);
- age at onset of migraine <50 years;
- migraine must have been present for at least ≥ 12 months;
- treated with CGRP-MAbs (erenumab, fremanezumab or galcanezumab) according to clinical practice criteria for 90-180 days since the first subcutaneous administration (this time range was chosen to ensure a stable CGRP pathway inhibition);
- reporting >4 monthly migraine days in the last 30 days of observation despite treatment with CGRP-MAbs;
- able to discriminate between migraine and tension-type headaches;
- written informed consent to participate in the study
Who cannot join
- any migraine preventive medication other than CGRP-MAbs;
- secondary migraine;
- epilepsy or any other neurologic condition that may be worsened by transcranial electrical stimulation;
- metallic head implants, cardiac pacemaker or any other device that could malfunction or be displaced by electrical stimulation;
- pregnancy or lactation.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effectiveness of tDCS and Monoclonals Antibodies Anti-CGRP as a Combined Treatment for Migraine: a Randomized, Double-blind, Sham-controlled Trial
Electrophysiological changes that occur in the brains of migraine patients, lead to the activation of nociceptive centers, including a peripheral neural structure, the trigeminal ganglion (TG), which releases pain-inducing peptides and mostly calcitonin gene-related peptide (CGRP). Monoclonal antibodies acting on the CGRP pathway (CGRP-MAbs) are the first drugs specifically designed for migraine, they inhibit CGRP release from the TG without entering the brain. Not all patients experience benefit from CGRP-MAbs treatment. For this reason, associating these drugs with a non-pharmacological treatment that acts centrally, such as transcranial direct current stimulation, could be effective.
The aim of the study is investigating how the migraine preventive treatment with CGRP-MAbs in association with tDCS, is effective to reduce headache days, days of disabling headache, intensity of pain and consumption of acute treatments. Migraine-related disability, quality of life, sleep disturbance and psychological aspects will also be evaluated. Patients will be randomized into two groups, one will receive active tDCS and one sham tDCS. Both patients and investigators will be blind to the treatment administered (double-blind).
Furthermore, will be evalutated the cortical mechanisms involved in migraine by directly modulating brain physiology via repetitive tDCS in patients with migraine on treatment with CGRP-MAbs. To fulfill this aim, we will assess the EEG correlates of the actual effects of the stimulation in a sham-controlled study, providing the EEG indexes linked to the altered and potentially restored cortical dynamics in migraine.
- Conditions
- Migraine
- Being tested
- Cathodal transcranial direct current stimulation, Sham cathodal transcranial direct current stimulation
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cathodal transcranial direct current stimulationDevice
The cathodal transcranial direct current stimulation protocol will consist in five daily sessions, each lasting 20 min. The montage will provide a bilateral stimulation on occipital areas, with the reference anodal electrodes positioned on the M1 areas. The stimulation will be applied via 4 conductive-rubber square electrodes (5x5 cm) placed in sponges saturated with high conductivity gel and connected to a battery-operated stimulator system. Direct current with maximal intensity of 1.5 mA with be provided for 20 minutes.
Sham cathodal transcranial direct current stimulationDevice
Sham stimulation will be performed by the same protocol as active stimulation; however, the device will be switched off 30 seconds after the beginning of stimulation. This way, the patient will experience the same sensations as with active stimulation without receiving actual stimulation.
| Study group | Role | What they receive |
|---|---|---|
| Cathodal transcranial direct current stimulation | Active comparator | Not described Receives: Device: Cathodal transcranial direct current stimulation |
| Sham transcranial direct current stimulation | Sham comparator | Not described Receives: Device: Sham cathodal transcranial direct current stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decrease in headache days
Difference between the active tDCS treated group and the sham tDCS treated group
Measured: 4 weeks
Decrease in disabling headache days
Difference between the active tDCS treated group and the sham tDCS treated group
Measured: 4 weeks
Decrease in mean 10-point Visual Analog Scale
Difference between the active tDCS treated group and the sham tDCS treated group in the 10-point Visual Analog Scale (0 to 10 points, where 0 means "no pain at all" and 10 "maximum conceivable pain")
Measured: 4 weeks
Decrease in doses of acute treatment
Difference between the active tDCS treated group and the sham tDCS treated group
Measured: 4 weeks
Secondary outcomes (5)
Decrease in mean modified Migraine Disability Assessment Scale (mMIDAS) score
Difference between the active tDCS treated group and the sham tDCS treated group in the modified Migraine Disability Assessment Scale (mMIDAS).
mMIDAS is a self-administered questionnaire that contains five questions about the headache a patient had in the previous month, assessing the impact of migraine on three domains of daily activity: two questions for paid work or schoolwork, two questions for household work, and one question for family, social and leisure activities. The two questions for each of the first two groups assess, respectively, the number of days off due to headache, and the number of days in which the productivity was reduced by half or more. mMIDAS index is derived from the sum of the answers on the first five questions. This score defines patients in four categories of headache disability: little/none disability if the score is between 0 and 5; mild disability if between 6 and 10; moderate disability if between 11 and 20; and severe disability if greater than 20.
Measured: 4 weeks
Decrease in mean Headache Impact Test-6 (HIT-6) score
Difference between the active tDCS treated group and the sham tDCS treated group
Measured: 4 weeks
Decrease in mean Short Form Health Survey (SF-36) score
Difference between the active tDCS treated group and the sham tDCS treated group
Measured: 4 weeks
Decrease in mean Pittsburgh Sleep Quality Index (PSQI) score
Difference between the active tDCS treated group and the sham tDCS treated group
Measured: 4 weeks
Decrease in mean Hospital Anxiety and Depression Scale (HADS) score
Difference between the active tDCS treated group and the sham tDCS treated group.
HADS is a scale based upon 14 questions. A score from 0 to 21 is given to both anxiety and depression, where 0-7 scores are normal, 8-10 borderline, and 11-21 abnormal.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2021
- Study start16 May 2022
- Primary completion16 Jan 2023
- Study completion16 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of L'Aquila
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Simona Sacco, University of L'Aquila
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05161871
- Sponsor's protocol ID
- 201722 ID INT 193/21
- Status last verified
- Dec 2024
- First submitted
- 3 Dec 2021
- Last updated
- 5 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Ornello R, D'Atri A, De Icco R, De Santis F, Rosignoli C, Onofri A, Vaghi G, Cammarota F, Brancaccio C, Corrado M, Bighiani F, Grillo V, Sances G, Corigliano D, Salfi F, Tassorelli C, Ferrara M, Sacco S. Effectiveness of transcranial direct current stimulation and monoclonal antibodies acting on the CGRP as a combined treatment for migraine (TACTIC): Results of a randomized controlled trial. Cephalalgia. 2025 May;45(5):3331024251325567. doi: 10.1177/03331024251325567. Epub 2025 May 19.
PubMed 40384614Ornello R, Rosignoli C, Caponnetto V, Pistoia F, Ferrara M, D'Atri A, Sacco S. Effectiveness of Transcranial Direct Current Stimulation and Monoclonal Antibodies Acting on the CGRP as a Combined Treatment for Migraine (TACTIC): Protocol for a Randomized, Double-Blind, Sham-Controlled Trial. Front Neurol. 2022 May 10;13:890364. doi: 10.3389/fneur.2022.890364. eCollection 2022.
PubMed 35620782
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of tDCS and Monoclonals Antibodies Anti-CGRP as a Combined Treatment for Migraine: a Randomized, Double-blind, Sham-controlled Trial
- ClinicalTrials.gov ID
- NCT05161871
- Acronym / sponsor ID
- 201722 ID INT 193/21
- Conditions
- Migraine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of L'AquilaUniversity, hospital or other
- Study start
- 16 May 2022 (actual)
- Primary completion
- 16 Jan 2023 (actual)
- Study completion
- 16 Apr 2023 (actual)
- First posted
- 17 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Electrophysiological changes that occur in the brains of migraine patients, lead to the activation of nociceptive centers, including a peripheral neural structure, the trigeminal ganglion (TG), which releases pain-inducing peptides and mostly calcitonin gene-related peptide (CGRP). Monoclonal antibodies acting on the CGRP pathway (CGRP-MAbs) are the first drugs specifically designed for migraine, they inhibit CGRP release from the TG without entering the brain. Not all patients experience benefit from CGRP-MAbs treatment. For this reason, associating these drugs with a non-pharmacological treatment that acts centrally, such as transcranial direct current stimulation, could be effective.
The aim of the study is investigating how the migraine preventive treatment with CGRP-MAbs in association with tDCS, is effective to reduce headache days, days of disabling headache, intensity of pain and consumption of acute treatments. Migraine-related disability, quality of life, sleep disturbance and psychological aspects will also be evaluated. Patients will be randomized into two groups, one will receive active tDCS and one sham tDCS. Both patients and investigators will be blind to the treatment administered (double-blind).
Furthermore, will be evalutated the cortical mechanisms involved in migraine by directly modulating brain physiology via repetitive tDCS in patients with migraine on treatment with CGRP-MAbs. To fulfill this aim, we will assess the EEG correlates of the actual effects of the stimulation in a sham-controlled study, providing the EEG indexes linked to the altered and potentially restored cortical dynamics in migraine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cathodal transcranial direct current stimulation | Active comparator | Device: Cathodal transcranial direct current stimulation |
| Sham transcranial direct current stimulation | Sham comparator | Device: Sham cathodal transcranial direct current stimulation |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- male or female patients, aged between 40 and 70 years, referring to the Headache Center of the University of L'Aquila;
- a diagnosis of migraine with or without aura according to the International Classification of Headache Disorders, 3rd Edition (ICHD-3; https://ichd-3.org/);
- age at onset of migraine <50 years;
- migraine must have been present for at least ≥ 12 months;
- treated with CGRP-MAbs (erenumab, fremanezumab or galcanezumab) according to clinical practice criteria for 90-180 days since the first subcutaneous administration (this time range was chosen to ensure a stable CGRP pathway inhibition);
Key exclusion criteria (5 listed)
- any migraine preventive medication other than CGRP-MAbs;
- secondary migraine;
- epilepsy or any other neurologic condition that may be worsened by transcranial electrical stimulation;
- metallic head implants, cardiac pacemaker or any other device that could malfunction or be displaced by electrical stimulation;
- pregnancy or lactation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cathodal transcranial direct current stimulationThe cathodal transcranial direct current stimulation protocol will consist in five daily sessions, each lasting 20 min. The montage will provide a bilateral stimulation on occipital areas, with the reference anodal electrodes positioned on the M1 areas. The stimulation will be applied via 4 conductive-rubber square electrodes (5x5 cm) placed in sponges saturated with high conductivity gel and connected to a battery-operated stimulator system. Direct current with maximal intensity of 1.5 mA with be provided for 20 minutes. | Device | Cathodal transcranial direct current stimulation |
| Sham cathodal transcranial direct current stimulationSham stimulation will be performed by the same protocol as active stimulation; however, the device will be switched off 30 seconds after the beginning of stimulation. This way, the patient will experience the same sensations as with active stimulation without receiving actual stimulation. | Device | Sham transcranial direct current stimulation |
Primary outcome
Decrease in headache days
Time frame: 4 weeks
Difference between the active tDCS treated group and the sham tDCS treated group
Decrease in disabling headache days
Time frame: 4 weeks
Difference between the active tDCS treated group and the sham tDCS treated group
Decrease in mean 10-point Visual Analog Scale
Time frame: 4 weeks
Difference between the active tDCS treated group and the sham tDCS treated group in the 10-point Visual Analog Scale (0 to 10 points, where 0 means "no pain at all" and 10 "maximum conceivable pain")
Decrease in doses of acute treatment
Time frame: 4 weeks
Difference between the active tDCS treated group and the sham tDCS treated group
5 secondary outcomes
Decrease in mean modified Migraine Disability Assessment Scale (mMIDAS) score
Time frame: 4 weeks
Decrease in mean Headache Impact Test-6 (HIT-6) score
Time frame: 4 weeks
Decrease in mean Short Form Health Survey (SF-36) score
Time frame: 4 weeks
Decrease in mean Pittsburgh Sleep Quality Index (PSQI) score
Time frame: 4 weeks
Decrease in mean Hospital Anxiety and Depression Scale (HADS) score
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2024.
- Derived from this study: PubMed 40384614Ornello R, D'Atri A, De Icco R, De Santis F, Rosignoli C, Onofri A, Vaghi G, Cammarota F, Brancaccio C, Corrado M, Bighiani F, Grillo V, Sances G, Corigliano D, Salfi F, Tassorelli C, Ferrara M, Sacco S. Effectiveness of transcranial direct current stimulation and monoclonal antibodies acting on the CGRP as a combined treatment for migraine (TACTIC): Results of a randomized controlled trial. Cephalalgia. 2025 May;45(5):3331024251325567. doi: 10.1177/03331024251325567. Epub 2025 May 19.
- Derived from this study: PubMed 35620782Ornello R, Rosignoli C, Caponnetto V, Pistoia F, Ferrara M, D'Atri A, Sacco S. Effectiveness of Transcranial Direct Current Stimulation and Monoclonal Antibodies Acting on the CGRP as a Combined Treatment for Migraine (TACTIC): Protocol for a Randomized, Double-Blind, Sham-Controlled Trial. Front Neurol. 2022 May 10;13:890364. doi: 10.3389/fneur.2022.890364. eCollection 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cathodal transcranial direct current stimulation in people with Migraine, run by University of L'Aquila at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Decrease in headache days (time frame: 4 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05161871, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2024.