Artificial Intelligence to Predict Surgical Outcomes and Assess Pain Neuromodulation in Trigeminal Neuralgia Subjects

February 25, 2026 updated by: Prof. Massimo Filippi, IRCCS San Raffaele
Trigeminal neuralgia (TN) is the most common cause of facial pain. Medical treatment is the first therapeutic choice whereas surgery, including Gamma Knife radiosurgery (GKRS), is indicated in case of pharmacological therapy failure. However, about 20% of subjects lack adequate pain relief after surgery. Virtual reality (VR) technology has been explored as a novel tool for reducing pain perception and might be the breakthrough in treatment-resistant cases. The investigators will conduct a prospective randomized comparative study to detect the effectiveness of GKRS aided by VR-training vs GKRS alone in TN patients. In addition, using MRI and artificial intelligence (AI), the investigators will identify pre-treatment abnormalities of central nervous system circuits associated with pain to predict response to treatment. The investigators expect that brain-based biomarkers, with clinical features, will provide key information in the personalization of treatment options and bring a huge impact in the management and understanding of pain in TN.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20132
        • IRCCS San Raffaele

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • diagnosis of TN according to the International Classification of Headache Disorders, third edition (ICHD-3) criteria;
  • age >18 years;
  • indication to undergo radiosurgical treatment;
  • willingness and ability to comply with scheduled visits and other trial procedures.

Exclusion Criteria:

  • Any person unable to lie still within the environment of the MRI scanner for the required period to perform the study and those where MRI scanning is contraindicated;
  • metal implants, pacemaker, etc.;
  • Pregnancy or breastfeeding;
  • Any significant psychiatric disease;
  • Use of illicit drugs;
  • Brain pathology shown by brain MRI and/or neurophysiological examination;
  • Any person unable to understand and follow the instructions of the investigators;
  • Any other condition according to the Investigator would make the subject unsuitable for the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GKRS-VR training
GKRS-VR group will undergo GKRS and neuromodulation based on Virtual Reality sensorimotor rehabilitation using an immersive system
Procedure: GKRS-VR training
One month after radiosurgery, GKRS-VR subjects will receive neuromodulation treatment twice a week (30' per time), for 8 consecutive weeks followed by 9 months of remote rehabilitation. GKRS-VR group will perform neuromodulation based on VR sensorimotor rehabilitation using an immersive system developed ad-hoc. Treatments will include voluntary mimic movements reinforced by VR augmented feedback, consisting in the reflection of a real-time avatar animation, multiplied when needed, associated with different targets to reach based on specific facial gestures. The execution of motion multiplier on avatar will be allowed in order to personalize treatments, emphasizing a graded exposure to pain perception. In addition, the investigators will develop a dedicated mobile-application for remote rehabilitation with the aim of prescribing VR augmented feedback home exercises and immersive VR pain neuromodulation.
Active Comparator: Control Group
Control group (CT) will undergo only GKRS
Procedure: Control Group
Control Group will undergo only radiosurgery with no rehabilitation and they will perform only clinical evaluation at study entry, after three months and one year.
No Intervention: Healthy subjects
Age- and sex-matched healthy subjects recruited to compare neuropsychological,clinical and structural/functional magnetic resonance imaging characteristics at baseline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Numeric Rating Scale for pain (NRS) changes
Time Frame: Baseline, month 3 and month 12
Changes in time in the Numeric rating scale (NRS): a pain screening tool, commonly used to assess pain severity at that moment in time using a 0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable"
Baseline, month 3 and month 12
Barrow Neurological Institute (BNI) pain score changes
Time Frame: Baseline, month 3 and month 12
Changes in time in the Barrow Neurological Institute (BNI) pain intensity scale to assess the level of pain in patients with trigeminal neuralgia. BNI values I-III were considered to indicate good outcomes whereas BNI values IV and V indicate poor response to treatment.
Baseline, month 3 and month 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
McGill Pain Questionnaire (MPQ) changes
Time Frame: Baseline, month 3 and month 12
The McGill Pain Questionnaire (MPQ) can be used to evaluate a person experiencing significant pain. It can be used to monitor the pain over time and to determine the effectiveness of any intervention. The users are presented with a list of 78 words in 20 sections that are related to pain.The users mark the words that best describe their pain (multiple markings are allowed). Among the words, sections of these words signify different components of pain, namely, Sensory (sections 1-10), Affective (sections 11-15), Evaluative (section 16), and Miscellaneous (sections 17-20).
Baseline, month 3 and month 12
Pain Catastrophizing Scale (PCS)
Time Frame: Baseline, month 3 and month 12
The Pain Catastrophizing Scale (PCS) assesses the extent of catastrophic thinking. It is a 13-item scale, with a total range of 0 to 52. Higher scores are associated with higher amounts of pain catastrophizing.
Baseline, month 3 and month 12
Central Sensitization Inventory (CSI) changes
Time Frame: Baseline, month 3 and month 12
The Central Sensitisation Inventory (CSI) is a self-report outcome measure designed to identify patients who have symptoms that may be related to central sensitisation.The CSI consists of two parts: Part A includes 25 questions related to common central sensitivity syndromes symptoms.Part B determines if the patient has been diagnosed with certain central sensitivity syndromes disorders or related disorders, such as anxiety and depression.
Baseline, month 3 and month 12
Tampa Scale of Kinesiophobia (TSK) changes
Time Frame: Baseline, month 3 and month 12
The Tampa Scale for Kinesiophobia (TSK) is a 17-item questionnaire that quantifies fear of movement. Individual item scores range from 1-4, with the negatively worded items (4,8,12,16) having a reverse scoring (4-1). The 17 item TSK total scores range from 17 to 68 where the lowest 17 means no or negligible kinesiophobia, and the higher scores indicate an increasing degree of kinesiophobia.
Baseline, month 3 and month 12
Craniofacial Pain and Disability Inventory (CFPDI) changes
Time Frame: Baseline, month 3 and month 12
Craniofacial Pain and Disability Inventory (CF-PDI) can be used in research and clinical practice for the assessment of patients with craniofacial pain. It is a 21-item measure and patients give their answers using a 4-point Likert scale scoring from 1 (no problem) to 4 (maximum problem). The scale presents two factors, named Pain and disability (14 items) and Jaw functional status (7 items). The scores of the responses are added with higher scores indicating greater problems
Baseline, month 3 and month 12
Penn Facial Pain Scale (PFPS) changes
Time Frame: Baseline, month 3 and month 12
The Penn Facial Pain Scale (Penn-FPS) was originally developed in order to fully assess the impact of trigeminal neuralgia pain on patients' health-related quality of life. It is a 7-item scale, with a total range of 0 to 10.
Baseline, month 3 and month 12
Percentage of displacement of virtual face landmarks
Time Frame: Baseline, month 3 and month 12
Percentage of displacement of virtual face landmarks
Baseline, month 3 and month 12
12-item Allodynia Symptom Checklist (ASC-12) scale changes
Time Frame: Baseline, month 3 and month 12
presence of allodynia and hypoesthesia; It is a 12-item scale, with a total range of 0 to 12.
Baseline, month 3 and month 12
Trigeminal reflexes testing
Time Frame: Baseline, month 3 and month 12
A series of reflex responses after electrical stimulation of the ophthalmic division (R1 and R2) and maxillary/mandibular division (SP1 and SP2) of the trigeminal nerve
Baseline, month 3 and month 12
Longitudinal changes of brain gray matter volumes
Time Frame: Baseline, month 3 and month 12
3D T1-weighted sequence wil be used to evaluate cortical thickness and subcortical volume changes
Baseline, month 3 and month 12
Longitudinal changes of white matter microstructural abnormalities
Time Frame: Baseline, month 3 and month 12
White matter damage will be evaluated on diffusion-tensor MRI sequence
Baseline, month 3 and month 12
Resting-State Functional Connectivity MRI changes
Time Frame: Baseline, month 3 and month 12
Longitudinal changes will be evaluated on functional MRI sequences
Baseline, month 3 and month 12
Functional MRI changes
Time Frame: Baseline, month 3 and month 12
Functional MRI will be acquired on a 3T scanner during the performance of a task, in which participants will be asked to observe facial gestures during activities of daily living or specific movements different for each subject depending on which action triggers the facial pain.
Baseline, month 3 and month 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 6, 2023

Primary Completion (Estimated)

November 30, 2026

Study Completion (Estimated)

April 30, 2027

Study Registration Dates

First Submitted

March 29, 2023

First Submitted That Met QC Criteria

April 11, 2023

First Posted (Actual)

April 12, 2023

Study Record Updates

Last Update Posted (Actual)

February 27, 2026

Last Update Submitted That Met QC Criteria

February 25, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GR-2021-12374601

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Magnetic Resonance Imaging

Clinical Trials on GKRS-VR training

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Morocco

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe