Refractory Chronic Cluster Headache: Exploring the Potential of Repetitive Transcranial Magnetic Stimulation

Evaluating Repetitive Transcranial Magnetic Stimulation for Refractory Chronic Cluster Headache Prevention: Insights From a Randomised Crossover Pilot Trial

The goal of this clinical trial is to learn if drug ABC works to treat severe asthma in adults. It will also learn about the safety of drug ABC. The main questions it aims to answer are:

Does Transcranial Magnetic Stimulation lower the number of attacks per week in patients with refractory cluster headache ?

Researchers will compare transcranial magnetic stimlation to a sham stimulation (a look-alike stimulation) to see if it works to prevent attacks of cluster headache.

Participants will:

Recieve stimulation for 10 minutes for 10 consecutive working days in 2 periods of time, separated by a 1 month washout period.

Visit the clinic for each treatment day. Keep a diary of their symptoms and the number of times they use a rescue medication

Study Overview

• Status: Completed
• Conditions: Refractory Chronic Cluster Headache
• Intervention / Treatment: Device: Repetitive Transcranial Magnetic Stimulation; Device: Sham Stimulation

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain
    • Hospital Universitario La Paz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years of age or older
• Diagnosed with Chronic Cluster Headache (CCH) based on the International Classification of Headache Disorders 3rd Edition
• Diagnosed with refractory CCH based on the European Headache Federation criteria of 2014.

Exclusion Criteria:

• History of epilepsy.
• Concomitant diagnosis of any other headache (if the patient was unable to differentiate between them).
• Carriers of any electronic device, or any additional contraindication for Transcranial Magnetic Stimulation, such as pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sequence A; The study consisted of two treatment periods (rTMS and sham stimulation), separated by a one-month washout period, and organized into two sequences (A and B) Sequence A: rTMS → washout → sham. Sequence B: sham → washout → rTMS.	Device: Repetitive Transcranial Magnetic Stimulation; Stimulation sessions were performed using a YINGCHI M-100 Ultimate device with liquid-cooled figure-8 coils. Patients attended 10-minute sessions daily for 10 consecutive working days. For rTMS, stimulation was delivered at an excitatory frequency of 10 Hz, targeting the M1, contralateral to the side of pain in the facial region. Each session consisted of the following steps.; 10 series: 60 pulses per series (600 pulses in total).; Rest intervals: 60 seconds between series.; Intensity: 70% of the resting motor threshold (RMT). RMT was determined using single-pulse stimulation over the M1 region controlling the abductor pollicis brevis muscle, localized via neuronavigation. The threshold was de-fined as the lowest stimulator intensity producing a motor-evoked potential amplitude >50 µV in at least 5 of 10 trials.; Device: Sham Stimulation; Sham Stimulation: The same device and protocol used for intervention protocol with Repetitive Transcranial Magnetic Stimulation were used for sham stimulation, but no active stimulation was delivered. The equipment produced identical sounds and appearances, thereby ensuring blinding.
Other: Sequence B; Sequence B: sham → washout → rTMS.	Device: Repetitive Transcranial Magnetic Stimulation; Stimulation sessions were performed using a YINGCHI M-100 Ultimate device with liquid-cooled figure-8 coils. Patients attended 10-minute sessions daily for 10 consecutive working days. For rTMS, stimulation was delivered at an excitatory frequency of 10 Hz, targeting the M1, contralateral to the side of pain in the facial region. Each session consisted of the following steps.; 10 series: 60 pulses per series (600 pulses in total).; Rest intervals: 60 seconds between series.; Intensity: 70% of the resting motor threshold (RMT). RMT was determined using single-pulse stimulation over the M1 region controlling the abductor pollicis brevis muscle, localized via neuronavigation. The threshold was de-fined as the lowest stimulator intensity producing a motor-evoked potential amplitude >50 µV in at least 5 of 10 trials.; Device: Sham Stimulation; Sham Stimulation: The same device and protocol used for intervention protocol with Repetitive Transcranial Magnetic Stimulation were used for sham stimulation, but no active stimulation was delivered. The equipment produced identical sounds and appearances, thereby ensuring blinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in number of attacks per week	The mean change in the number of attacks per week at the end of each treatment period was compared with the baseline, from the time of informed consent until the last follow-up moment (3 months after the end of the second treatment period).	From enrollment to the end to follow up period, at 3 months after last treatment period (week 8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing the reduction in symptomatic medication use.	The use of symptomatic medication was assessed through electronic questionnaires completed by the patient. The mean change in the use of symptomatic medication at the end of each treatment period was compared with the baseline, from the time of informed consent until the last follow-up moment (3 months after the end of the second treatment period).	From enrollment to the end of follow up period, at 3 months after second treatment period (week 8)
To assess the reduction in intensity of cluster headache attacks	The intensity of the attacks of cluster headache was assessed through electronic questionnaires completed by the patient, using the visual analogue scale from 1 to 10. The mean change in the intensity at the end of each treatment period was compared with the baseline, from the time of informed consent until the last follow-up moment (3 months after the end of the second treatment period).	From enrollment to the end of follow up period, at 3 months after second treatment period (week 8)
To assess the change in duration in cluster headache attacks	The duration of the attacks of cluster headache was assessed through electronic questionnaires completed by the patient (minutes). The mean change in the duration at the end of each treatment period was compared with the baseline, from the time of informed consent until the last follow-up moment (3 months after the end of the second treatment period).	From enrollment to the end of follow up period, at 3 months after second treatment period (week 8)
To assess the tolerability to treatment	The tolerability to treatment was assessed through electronic questionnaires completed by the patient, reporting any symptom experienced during treatment. It was then evaluated its possible relationship to rTMS. The adverse effects were evaluated from the time of informed consent until the last follow-up moment (3 months after the end of the second treatment period).	From enrollment to the end of follow up period, at 3 months after second treatment period (week 8)

Collaborators and Investigators

• Sponsor: Hospital Universitario La Paz

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2023
• Primary Completion (Actual): May 31, 2024
• Study Completion (Actual): May 31, 2024

Study Registration Dates

• First Submitted: March 25, 2025
• First Submitted That Met QC Criteria: March 31, 2025
• First Posted (Estimated): April 8, 2025

Study Record Updates

• Last Update Posted (Estimated): April 8, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Trigeminal Autonomic Cephalalgias; Headache; Cluster Headache
• Other Study ID Numbers: PI-6581

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No