Clinical trial NCT05161871: Transcranial Direct Current Stimulation Plus Monoclonal Antibodies Acting on the CGRP Pathway for Migraine
Official title: Effectiveness of tDCS and Monoclonals Antibodies Anti-CGRP as a Combined Treatment for Migraine: a Randomized, Double-blind, Sham-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Migraine
Lead sponsor: University of L'Aquila
Sponsor class: OTHER
First posted: 2021-12-17
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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). 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Decrease in headache days
timeFrame: 4 weeks
measure: Decrease in disabling headache days
timeFrame: 4 weeks
measure: Decrease in mean 10-point Visual Analog Scale
timeFrame: 4 weeks
measure: Decrease in doses of acute treatment
timeFrame: 4 weeks
Secondary outcomes:
measure: Decrease in mean modified Migraine Disability Assessment Scale (mMIDAS) score
timeFrame: 4 weeks
measure: Decrease in mean Headache Impact Test-6 (HIT-6) score
timeFrame: 4 weeks
measure: Decrease in mean Short Form Health Survey (SF-36) score
timeFrame: 4 weeks
measure: Decrease in mean Pittsburgh Sleep Quality Index (PSQI) score
timeFrame: 4 weeks
measure: Decrease in mean Hospital Anxiety and Depression Scale (HADS) score
timeFrame: 4 weeks
Other outcomes:
measure: Change in occipital electroencephalographic (EEG) signal power at 8-13 Hz frequency after vs before tDCS
timeFrame: 4 weeks
Locations:
city: L'Aquila
country: Italy
facility: University of L'Aquila
Study officials:
References:
citation: Ornello 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.