An observational study in Pain Management and Psychiatric Comorbidities, sponsored by Galileo Medical Center. Completed at 1 site in Bulgaria. Open to participants aged 18 Years to 83 Years. Per ClinicalTrials.gov, last updated 2026-11-03.
Sponsored by Galileo Medical Center · Observational
Brief Summary
The goal of this clinical trial is to learn if an accelerated, dual-protocol high-frequency repetitive transcranial magnetic stimulation (rTMS) intervention can treat and achieve long-term pain relief (analgesia) in patients with pharmacologically refractory primary Trigeminal Neuralgia (TN). The main questions it aims to answer are:
Participants will:
Project Summary: Repetitive Transcranial Magnetic Stimulation (rTMS) for Refractory Trigeminal Neuralgia
Abstract / Executive Summary
This project evaluates the therapeutic efficacy and long-term analgesic effects of an innovative, high-intensity repetitive Transcranial Magnetic Stimulation (rTMS) protocol for patients with refractory Trigeminal Neuralgia (TN). Using the high-performance Neuro-MS/D magnetic stimulator (Neurosoft), the study implements a dual-protocol, accelerated schedule delivered twice daily over 5 business days. Patients undergo a rigorous, multi-stage screening process (including independent neurological exams and EEG) to ensure safety and confirm diagnosis. Therapeutic outcomes, including pain intensity, spatial distribution, anxiety, depression, and overall quality of life, are systematically tracked at baseline, 1 month, and 3 months post-treatment using standardized clinical scales (VAS, BPI, HADS, QoLp, and PGIC). The ultimate goal is to establish a noninvasive neuromodulatory framework capable of inducing sustained, long-term analgesia for drug-resistant facial pain.
Background and Clinical Justification
Trigeminal Neuralgia (TN) is marked by excruciating, electric-shock-like paroxysmal pain confined to the distribution of one or more branches of the trigeminal nerve. When conventional pharmacological treatments (such as carbamazepine or oxcarbazepine) fail because of lack of efficacy or intolerable systemic side effects, the condition is classified as refractory TN.
Neurostimulation with rTMS offers a safe, noninvasive alternative. High-frequency rTMS applied over the primary motor cortex (M1) contralateral to the painful facial side has been shown to modulate the central pain matrix. It triggers long-term potentiation (LTP)-like plasticity, alters thalamocortical pathways, and activates descending inhibitory pain control systems. This project seeks to optimize these mechanisms by using a novel dual-frequency accelerated paradigm to maximize cumulative neuroplastic changes and prolong pain relief.
Study Design and Patient Workflow
The study uses a longitudinal, prospective design organized into four distinct phases over a 3-month observation window per participant:
[Phase 1: Pre-Screening] ➔ Independent Neurological Exam \& EEG Diagnostics
▼ [Phase 2: Baseline Assessment] ➔ Informed Consent \& Pre-treatment Psychometric Scales
▼ [Phase 3: Therapeutic Intervention] ➔ 10 rTMS Sessions (Twice daily for 5 consecutive days)
▼ [Phase 4: Follow-Up Monitoring] ➔ Re-evaluation at Month 1 and Month 3 Post-Intervention
Selection Criteria and Patient Screening
To ensure high internal validity and absolute patient safety, candidate selection is subject to strict eligibility criteria:
Technical Specifications \& Interventional rTMS Protocol
Brain stimulation is delivered using the Neuro-MS/D system manufactured by Neurosoft. The focal point of stimulation is the primary motor cortex (M1) on the side of the brain opposite the patient's affected facial side.
The treatment regimen consists of 10 sessions delivered over 5 consecutive working days. Each day, patients receive two distinct therapeutic blocks configured as follows:
Parameter Specification Protocol Layer 1 Protocol Layer 2 Stimulation Frequency 10 Hz (High-Frequency) 20 Hz (High-Frequency) Duration per Session 28 Minutes 9 Minutes Total Session Runtime 37 Minutes Anatomical Target Contralateral M1 Contralateral M1
Psychometric Evaluation \& Outcome Measures
Given the profound toll that chronic pain takes on a patient's mental health and social functioning, a multidimensional testing framework is applied. Given the profound toll chronic pain takes on a patient's mental health and social functioning, a multidimensional testing framework is used. Measurements are collected at three key intervals: Baseline (pre-treatment), Month 1, and Month 3.
The primary objective of this clinical trial is to achieve a statistically significant and sustained reduction in pain scores (measured by VAS and BPI) at short-term (1 month) and mid-term (3 months) checkpoints. By delivering combined 10 Hz and 20 Hz sequences via the Neurosoft Neuro-MS/D platform, this research aims to demonstrate that accelerated, dual-protocol stimulation yields superior analgesic durability compared with standard single-session regimens. Ultimately, the data generated will contribute to the standardization of non-invasive, non-pharmacological neuromodulation protocols within international clinical guidelines for refractory cranial neuropathies.
140 studies on the registry are indexed under Trigeminal Neuralgia; 44 are open to participants now.
This study's enrollment of 192 is above the median of 84 across 38 observational studies indexed under Trigeminal Neuralgia.
Browse Trigeminal Neuralgia studies →This is the only study on the registry with Galileo Medical Center as lead sponsor.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Nov 3, 2026. See what changed
Study Population Description The study population consists of adult outpatients aged 18 to 85 years diagnosed with severe, pharmacologically refractory primary unilateral Trigeminal Neuralgia (TN). Participants are recruited from specialized neurology clinics, tertiary headache centers, and neurosurgical referral channels.
This cohort represents individuals experiencing chronic, severe neuropathic facial pain that has failed to respond to standard guideline-based medical therapies (such as carbamazepine, oxcarbazepine, and secondary add-on agents) or who suffer from treatment-limiting side effects from these medications. The population reflects a real-world clinical sample of drug-resistant cranial neuropathy patients who have preserved cognitive capacity (MMSE ≥ 24) and have been cleared of any latent epileptic or structural brain risks via mandatory independent neurological and digital EEG screening.
Non-Probability Sample Consecutive Sampling
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
•All enrolled participants are assigned to this single active treatment group. Patients receive a high-density, accelerated course of non-invasive brain stimulation consisting of 10 therapeutic sessions delivered twice daily over 5 consecutive working days. Stimulation is targeted at the primary motor cortex (M1) contralateral (opposite) to the clinically reported facial pain using the Neurosoft Neuro-MS/D magnetic stimulator. Each treatment day delivers a total volume of 9,000 stimuli, split across two sessions separated by a strict 45-50 minute rest interval. * Intervention Type: Device (Repetitive Transcranial Magnetic Stimulation) * Intervention Name: Neurosoft Neuro-MS/D Dual-Frequency Paradigm * Intervention Details: Brain stimulation is delivered via a Neurosoft liquid-cooled figure-of-eight coil calibrated at 80% to 90% of the patient's individual resting motor threshold (rMT).
• Arm Description: Participants assigned to this group do not receive rTMS neuromodulation. Instead, they continue with optimized standard pharmacological treatment for primary Trigeminal Neuralgia as managed by their primary neurologist. This includes maintaining optimized, stable baseline dosages of standard first-line membrane-stabilizing anticonvulsant agents (such as carbamazepine or oxcarbazepine) and/or secondary adjunctive therapies (such as gabapentin, pregabalin, baclofen, or lamotrigine). This group serves as the clinical baseline comparator to isolate the therapeutic effect size, onset speed, and long-term durability of the accelerated rTMS intervention versus conventional pharmacological management over the 3-month tracking timeline. * Intervention Type: Drug (Standard Pharmacotherapy) * Intervention Name: Guideline-Based Medical Management * Intervention Details: Patients undergo regular clinical check-ups and medical management according to national guidelines.
Change from Baseline in Patient-Reported Facial Pain Intensity via the Visual Analog Scale (VAS)
The primary efficacy endpoint is the sub-acute reduction of self-reported facial pain intensity. Pain is measured using a standardized 100 mm Visual Analog Scale (VAS), where 0 represents "No Pain," and 100 represents "The Worst Imaginable Pain." Patients draw a vertical line indicating their average pain over the preceding 24 hours. The distance is measured in millimeters to provide a continuous numeric value.
Time frame: Baseline (T₀, prior to the first rTMS session) and 1-Month Post-Treatment (T₂, exactly 30 days after the final rTMS session).
Long-Term Durability of Analgesia via the Visual Analog Scale (VAS)
This measure tracks the persistence of the therapeutic effect or any potential neuroplastic decay over time. It evaluates if the dual-frequency accelerated paradigm sustains a statistically valid reduction in pain scores into the third month following the intervention.
Time frame: Baseline (T₀) and 3-Months Post-Treatment (T₃, exactly 90 days after the final rTMS session).
Change from Baseline in Pain Interference and Distribution via the Brief Pain Inventory
The BPI evaluates the sensory-discriminative dimension of pain. It measures both pain intensity (worst, least, average, and current pain on a 0-10 scale) and pain interference-quantifying how much the facial pain disrupts seven functional domains of daily life (general activity, walking, mood, normal work, relationships, sleep, and enjoyment of life). It also tracks changes in the spatial distribution and trigger zones mapped on the BPI body outline chart.
Time frame: Baseline (T₀), Immediate Post-Treatment (T₁, Day 5), 1-Month Post-Treatment (T₂), and 3-Months Post-Treatment (T₃).
Change from Baseline in Emotional Distress and Psychological Co-morbidities via the Hospital Anxiety and Depression Scale (HADS)
The HADS is a 14-item self-rating scale used to isolate and quantify levels of anxiety (HADS-A, 7 items) and depression (HADS-D, 7 items) triggered by prolonged exposure to chronic, severe pain. Each item is scored from 0 to 3, yielding separate subscale totals from 0 to 21. Higher scores indicate greater psychological distress (scores ≥ 11 signify severe, clinically relevant states).
Time frame: Baseline (T₀), 1-Month Post-Treatment (T₂), and 3-Months Post-Treatment (T₃).
Change from Baseline in Health-Related Quality of Life via the Quality of Life Pain Scale (QoLp)
The QoLp scale evaluates the broader functional, social, and economic toll of refractory Trigeminal Neuralgia on the patient's well-being. It measures multi-item domains including physical independence, social integration, occupational capability, and cognitive clarity under chronic pain conditions.
Time frame: Baseline (T₀), 1-Month Post-Treatment (T₂), and 3-Months Post-Treatment (T₃).
Patient Global Impression of Clinical Improvement via the Patient Global Impression of Change (PGIC) Scale
The PGIC is a single-item, 7-point categorical scale capturing the patient's holistic self-assessment of the overall shift in their medical condition since the start of the accelerated rTMS therapy. Scores range from 1 ("Very Much Improved") to 7 ("Very Much Worse"). A successful clinical response is defined as achieving a rating of 1 or 2.
Time frame: Immediate Post-Treatment (T₁, Day 5), 1-Month Post-Treatment (T₂), and 3-Months Post-Treatment (T₃).
Plan to share: Undecided
Ran from Mar 2023 to primary completion in Mar 2026, 36 months.
Of 19 observational studies under Trigeminal Neuralgia, half reached primary completion within 37 months of starting (the median), counting those still running; a quarter within 24 and three quarters within 59. This study's 36 months is close to that.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is completed, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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