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

NCT05810428 | Enrolling By Invitation DMC

• 1 other identifier: GR-2021-12374601
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Trigeminal Neuralgia; Trigeminal Nerve Diseases; Virtual Reality; Artificial Intelligence; Radiosurgery; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (2)

• Numeric Rating Scale for pain (NRS) changes

  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

  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 Outcomes (13)

• McGill Pain Questionnaire (MPQ) changes

  Baseline, month 3 and month 12

• Pain Catastrophizing Scale (PCS)

  Baseline, month 3 and month 12

• Central Sensitization Inventory (CSI) changes

  Baseline, month 3 and month 12

• Tampa Scale of Kinesiophobia (TSK) changes

  Baseline, month 3 and month 12

• Craniofacial Pain and Disability Inventory (CFPDI) changes

  Baseline, month 3 and month 12

Study Arms (3)

GKRS-VR training

EXPERIMENTAL

GKRS-VR group will undergo GKRS and neuromodulation based on Virtual Reality sensorimotor rehabilitation using an immersive system

Procedure: GKRS-VR training

Control Group

ACTIVE COMPARATOR

Control group (CT) will undergo only GKRS

Procedure: Control Group

Healthy subjects

NO INTERVENTION

Age- and sex-matched healthy subjects recruited to compare neuropsychological,clinical and structural/functional magnetic resonance imaging characteristics at baseline.

Interventions

GKRS-VR training PROCEDURE

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.

GKRS-VR training

Control Group PROCEDURE

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.

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS San Raffaele

Milan, 20132, Italy

Location

Related Publications (11)

• Barzaghi LR, Pompeo E, Albano L, Del Vecchio A, Mortini P. Gamma Knife radiosurgery for cluster-tic syndrome unresponsive to medical treatment: illustrative case. J Neurosurg Case Lessons. 2021 Jul 26;2(4):CASE2191. doi: 10.3171/CASE2191. eCollection 2021 Jul 26.

  PMID: 35854679 BACKGROUND

• Barzaghi LR, Albano L, Scudieri C, Gigliotti CR, Nadin F, Del Vecchio A, Mortini P. Gamma Knife Radiosurgery for Trigeminal Neuralgia: Role of Trigeminal Length and Pontotrigeminal Angle on Target Definition and on Clinical Effects. World Neurosurg. 2020 Oct;142:e140-e150. doi: 10.1016/j.wneu.2020.06.147. Epub 2020 Jun 26.

  PMID: 32599193 BACKGROUND

• Albano L, Agosta F, Basaia S, Castellano A, Messina R, Parisi V, Barzaghi LR, Falini A, Mortini P, Filippi M. Alterations of brain structural MRI are associated with outcome of surgical treatment in trigeminal neuralgia. Eur J Neurol. 2022 Jan;29(1):305-317. doi: 10.1111/ene.15105. Epub 2021 Sep 24.

  PMID: 34519132 BACKGROUND

• Filippi M, Agosta F, Scola E, Canu E, Magnani G, Marcone A, Valsasina P, Caso F, Copetti M, Comi G, Cappa SF, Falini A. Functional network connectivity in the behavioral variant of frontotemporal dementia. Cortex. 2013 Oct;49(9):2389-401. doi: 10.1016/j.cortex.2012.09.017. Epub 2012 Oct 24.

  PMID: 23164495 BACKGROUND

• Filippi M, Basaia S, Canu E, Imperiale F, Meani A, Caso F, Magnani G, Falautano M, Comi G, Falini A, Agosta F. Brain network connectivity differs in early-onset neurodegenerative dementia. Neurology. 2017 Oct 24;89(17):1764-1772. doi: 10.1212/WNL.0000000000004577. Epub 2017 Sep 27.

  PMID: 28954876 BACKGROUND

• Agosta F, Spinelli EG, Marjanovic IV, Stevic Z, Pagani E, Valsasina P, Salak-Djokic B, Jankovic M, Lavrnic D, Kostic VS, Filippi M. Unraveling ALS due to SOD1 mutation through the combination of brain and cervical cord MRI. Neurology. 2018 Feb 20;90(8):e707-e716. doi: 10.1212/WNL.0000000000005002. Epub 2018 Jan 24.

  PMID: 29367447 BACKGROUND

• Basaia S, Agosta F, Cividini C, Trojsi F, Riva N, Spinelli EG, Moglia C, Femiano C, Castelnovo V, Canu E, Falzone Y, Monsurro MR, Falini A, Chio A, Tedeschi G, Filippi M. Structural and functional brain connectome in motor neuron diseases: A multicenter MRI study. Neurology. 2020 Nov 3;95(18):e2552-e2564. doi: 10.1212/WNL.0000000000010731. Epub 2020 Sep 10.

  PMID: 32913015 BACKGROUND

• Basaia S, Agosta F, Diez I, Bueicheku E, d'Oleire Uquillas F, Delgado-Alvarado M, Caballero-Gaudes C, Rodriguez-Oroz M, Stojkovic T, Kostic VS, Filippi M, Sepulcre J. Neurogenetic traits outline vulnerability to cortical disruption in Parkinson's disease. Neuroimage Clin. 2022;33:102941. doi: 10.1016/j.nicl.2022.102941. Epub 2022 Jan 19.

  PMID: 35091253 BACKGROUND

• Basaia S, Agosta F, Wagner L, Canu E, Magnani G, Santangelo R, Filippi M; Alzheimer's Disease Neuroimaging Initiative. Automated classification of Alzheimer's disease and mild cognitive impairment using a single MRI and deep neural networks. Neuroimage Clin. 2019;21:101645. doi: 10.1016/j.nicl.2018.101645. Epub 2018 Dec 18.

  PMID: 30584016 BACKGROUND

• Alemanno F, Houdayer E, Emedoli D, Locatelli M, Mortini P, Mandelli C, Raggi A, Iannaccone S. Efficacy of virtual reality to reduce chronic low back pain: Proof-of-concept of a non-pharmacological approach on pain, quality of life, neuropsychological and functional outcome. PLoS One. 2019 May 23;14(5):e0216858. doi: 10.1371/journal.pone.0216858. eCollection 2019.

  PMID: 31120892 BACKGROUND

• Emedoli D, Arosio M, Tettamanti A, Iannaccone S. Virtual Reality Augmented Feedback Rehabilitation Associated to Action Observation Therapy in Buccofacial Apraxia: Case Report. Clin Med Insights Case Rep. 2021 Feb 15;14:1179547621994579. doi: 10.1177/1179547621994579. eCollection 2021.

  PMID: 33642888 BACKGROUND

MeSH Terms

Conditions

Trigeminal Neuralgia; Trigeminal Nerve Diseases

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Facial Neuralgia; Facial Nerve Diseases; Mouth Diseases; Stomatognathic Diseases; Cranial Nerve Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Physiotherapist, neurologists, neuropsychologists, radiologist and biomedical engineering assessing the patients are blinded to group allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: Single centre, randomized controlled trial, assessor blinded. The investigators plan to enroll 50 TN patients with indications to undergo surgical treatment. Fifty TN participants will be randomly allocated into two groups: individuals in the experimental group (GKRS-VR) will undergo GKRS followed by immersive VR-based sensorimotor neuromodulation training, whilst control group (CT) will undergo only GKRS. A group of 50 age- and sex-matched controls will also be recruited.

Study Record Dates

• First Submitted: March 29, 2023
• First Posted: April 12, 2023
• Study Start: April 6, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)