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

Not Applicable
Completed
Conditions
Migraine
Interventions
Device: Cathodal transcranial direct current stimulation
Device: Sham cathodal transcranial direct current stimulation
Registration Number
NCT05161871
Lead Sponsor
University of L'Aquila
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cathodal transcranial direct current stimulationCathodal transcranial direct current stimulation-
Sham transcranial direct current stimulationSham cathodal transcranial direct current stimulation-
Primary Outcome Measures
NameTimeMethod
Decrease in headache days4 weeks

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

Decrease in mean 10-point Visual Analog Scale4 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 treatment4 weeks

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

Decrease in disabling headache days4 weeks

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

Secondary Outcome Measures
NameTimeMethod
Decrease in mean Headache Impact Test-6 (HIT-6) score4 weeks

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

Decrease in mean Short Form Health Survey (SF-36) score4 weeks

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

Decrease in mean Hospital Anxiety and Depression Scale (HADS) score4 weeks

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.

Decrease in mean modified Migraine Disability Assessment Scale (mMIDAS) score4 weeks

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.

Decrease in mean Pittsburgh Sleep Quality Index (PSQI) score4 weeks

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

Trial Locations

Locations (1)

University of L'Aquila

🇮🇹

L'Aquila, Italy

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