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

Primary Purpose

Trigeminal Neuralgia, Trigeminal Nerve Diseases, Virtual Reality

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
GKRS-VR training
Control Group
Sponsored by
IRCCS San Raffaele
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Trigeminal Neuralgia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • IRCCS San RaffaeleRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

No Intervention

Arm Label

GKRS-VR training

Control Group

Healthy subjects

Arm Description

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

Control group (CT) will undergo only GKRS

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

Outcomes

Primary Outcome Measures

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"
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.

Secondary Outcome Measures

McGill Pain Questionnaire (MPQ) changes
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).
Pain Catastrophizing Scale (PCS)
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.
Central Sensitization Inventory (CSI) changes
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.
Tampa Scale of Kinesiophobia (TSK) changes
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.
Craniofacial Pain and Disability Inventory (CFPDI) changes
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
Penn Facial Pain Scale (PFPS) changes
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.
Percentage of displacement of virtual face landmarks
Percentage of displacement of virtual face landmarks
12-item Allodynia Symptom Checklist (ASC-12) scale changes
presence of allodynia and hypoesthesia; It is a 12-item scale, with a total range of 0 to 12.
Trigeminal reflexes testing
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
Longitudinal changes of brain gray matter volumes
3D T1-weighted sequence wil be used to evaluate cortical thickness and subcortical volume changes
Longitudinal changes of white matter microstructural abnormalities
White matter damage will be evaluated on diffusion-tensor MRI sequence
Resting-State Functional Connectivity MRI changes
Longitudinal changes will be evaluated on functional MRI sequences
Functional MRI changes
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.

Full Information

First Posted
March 29, 2023
Last Updated
October 3, 2023
Sponsor
IRCCS San Raffaele
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1. Study Identification

Unique Protocol Identification Number
NCT05810428
Brief Title
Artificial Intelligence to Predict Surgical Outcomes and Assess Pain Neuromodulation in Trigeminal Neuralgia Subjects
Official Title
Artificial Intelligence to Predict Surgical Outcomes and Assess Pain Neuromodulation in Trigeminal Neuralgia Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 6, 2023 (Actual)
Primary Completion Date
November 30, 2025 (Anticipated)
Study Completion Date
April 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
IRCCS San Raffaele

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Trigeminal Neuralgia, Trigeminal Nerve Diseases, Virtual Reality, Artificial Intelligence, Radiosurgery, Magnetic Resonance Imaging

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
Outcomes Assessor
Masking Description
Physiotherapist, neurologists, neuropsychologists, radiologist and biomedical engineering assessing the patients are blinded to group allocation.
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GKRS-VR training
Arm Type
Experimental
Arm Description
GKRS-VR group will undergo GKRS and neuromodulation based on Virtual Reality sensorimotor rehabilitation using an immersive system
Arm Title
Control Group
Arm Type
Active Comparator
Arm Description
Control group (CT) will undergo only GKRS
Arm Title
Healthy subjects
Arm Type
No Intervention
Arm Description
Age- and sex-matched healthy subjects recruited to compare neuropsychological,clinical and structural/functional magnetic resonance imaging characteristics at baseline.
Intervention Type
Procedure
Intervention Name(s)
GKRS-VR training
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Control Group
Intervention Description
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.
Primary Outcome Measure Information:
Title
Numeric Rating Scale for pain (NRS) changes
Description
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"
Time Frame
Baseline, month 3 and month 12
Title
Barrow Neurological Institute (BNI) pain score changes
Description
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.
Time Frame
Baseline, month 3 and month 12
Secondary Outcome Measure Information:
Title
McGill Pain Questionnaire (MPQ) changes
Description
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).
Time Frame
Baseline, month 3 and month 12
Title
Pain Catastrophizing Scale (PCS)
Description
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.
Time Frame
Baseline, month 3 and month 12
Title
Central Sensitization Inventory (CSI) changes
Description
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.
Time Frame
Baseline, month 3 and month 12
Title
Tampa Scale of Kinesiophobia (TSK) changes
Description
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.
Time Frame
Baseline, month 3 and month 12
Title
Craniofacial Pain and Disability Inventory (CFPDI) changes
Description
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
Time Frame
Baseline, month 3 and month 12
Title
Penn Facial Pain Scale (PFPS) changes
Description
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.
Time Frame
Baseline, month 3 and month 12
Title
Percentage of displacement of virtual face landmarks
Description
Percentage of displacement of virtual face landmarks
Time Frame
Baseline, month 3 and month 12
Title
12-item Allodynia Symptom Checklist (ASC-12) scale changes
Description
presence of allodynia and hypoesthesia; It is a 12-item scale, with a total range of 0 to 12.
Time Frame
Baseline, month 3 and month 12
Title
Trigeminal reflexes testing
Description
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
Time Frame
Baseline, month 3 and month 12
Title
Longitudinal changes of brain gray matter volumes
Description
3D T1-weighted sequence wil be used to evaluate cortical thickness and subcortical volume changes
Time Frame
Baseline, month 3 and month 12
Title
Longitudinal changes of white matter microstructural abnormalities
Description
White matter damage will be evaluated on diffusion-tensor MRI sequence
Time Frame
Baseline, month 3 and month 12
Title
Resting-State Functional Connectivity MRI changes
Description
Longitudinal changes will be evaluated on functional MRI sequences
Time Frame
Baseline, month 3 and month 12
Title
Functional MRI changes
Description
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.
Time Frame
Baseline, month 3 and month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Massimo Filippi, MD
Phone
00390226433054
Email
filippi.massimo@hsr.it
First Name & Middle Initial & Last Name or Official Title & Degree
Silvia Basaia, PhD
Phone
00390226433051
Email
basaia.silvia@hsr.it
Facility Information:
Facility Name
IRCCS San Raffaele
City
Milan
ZIP/Postal Code
20132
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Massimo Filippi, MD
Phone
00390226433054
Email
filippi.massimo@hsr.it
First Name & Middle Initial & Last Name & Degree
Silvia Basaia, PhD
Phone
00390226433051
Email
basaia.silvia@hsr.it
First Name & Middle Initial & Last Name & Degree
Luigi Albano, MD,PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35854679
Citation
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.
Results Reference
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PubMed Identifier
32599193
Citation
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. Erratum In: World Neurosurg. 2021 Mar 4;:
Results Reference
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PubMed Identifier
34519132
Citation
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Artificial Intelligence to Predict Surgical Outcomes and Assess Pain Neuromodulation in Trigeminal Neuralgia Subjects

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