Transcranial Direct Current Stimulation Plus Monoclonal Antibodies Acting on the CGRP Pathway for Migraine

NCT05161871 | Completed

• 1 other identifier: 201722 ID INT 193/21
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Migraine

Outcome Measures

Primary Outcomes (4)

• Decrease in headache days

  Difference between the active tDCS treated group and the sham tDCS treated group

  4 weeks

• Decrease in disabling headache days

  Difference between the active tDCS treated group and the sham tDCS treated group

  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")

  4 weeks

• Decrease in doses of acute treatment

  Difference between the active tDCS treated group and the sham tDCS treated group

  4 weeks

Secondary Outcomes (5)

• Decrease in mean modified Migraine Disability Assessment Scale (mMIDAS) score

  4 weeks

• Decrease in mean Headache Impact Test-6 (HIT-6) score

  4 weeks

• Decrease in mean Short Form Health Survey (SF-36) score

  4 weeks

• Decrease in mean Pittsburgh Sleep Quality Index (PSQI) score

  4 weeks

• Decrease in mean Hospital Anxiety and Depression Scale (HADS) score

  4 weeks

Other Outcomes (1)

• Change in occipital electroencephalographic (EEG) signal power at 8-13 Hz frequency after vs before tDCS

  4 weeks

Study Arms (2)

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

Interventions

Cathodal transcranial direct current stimulation DEVICE

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.

Cathodal transcranial direct current stimulation

Sham cathodal transcranial direct current stimulation DEVICE

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.

Sham transcranial direct current stimulation

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of L'Aquila: lead

Study Sites (1)

University of L'Aquila

L’Aquila, 67100, Italy

Location

Related Publications (2)

• 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.

  PMID: 40384614 DERIVED

• 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.

  PMID: 35620782 DERIVED

MeSH Terms

Conditions

Migraine Disorders

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor of Neurology

Study Record Dates

• First Submitted: December 3, 2021
• First Posted: December 17, 2021
• Study Start: May 16, 2022
• Primary Completion: January 16, 2023
• Study Completion: April 16, 2023
• Last Updated: December 5, 2024

Record last verified: 2024-12

Locations

IT (1)