An Innovative Cognitive-Behavioral Treatment For Chronic Orofacial Pain

NCT ID: NCT07123233

Last Updated: 2026-02-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-24

Study Completion Date

2028-05-31

Brief Summary

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The present randomized clinical trial (RCT), conducted at the IRCCS Carlo Besta Neurological Institute, aims to evaluate the effectiveness of Pain Reprocessing Therapy (PRT), a form of psychological support/psychotherapy based on cognitive-behavioral therapy, which has already proven effective in the treatment of other types of primary chronic pain.

Chronic Primary Orofacial Pain (CPOP) is a rare and complex form of chronic pain that predominantly affects adult women and occurs without evident lesions, yet has a significant emotional and functional impact. It was recently classified among chronic primary pain conditions in the ICD-11 and is considered a form of nociplastic pain, associated with alterations in brain connectivity. At present, pharmacological treatments have shown limited effectiveness.

This randomized clinical trial (RCT), conducted at the IRCCS Carlo Besta Neurological Institute, aims to evaluate the effectiveness of Pain Reprocessing Therapy (PRT), a form of psychological support/psychotherapy based on cognitive-behavioral therapy, which has already proven effective in the treatment of other types of primary chronic pain.

Sixty participants, all diagnosed with CPOP according to ICD-11 criteria, will be selected and randomly assigned to two groups: one will receive PRT, the other will receive treatment as usual (TAU).

The primary outcome of the study is the assessment of pain intensity reduction. Secondary outcomes include a broad range of psychosocial variables: improvement in quality of life, reduction of anxiety-depressive symptoms, catastrophizing, and other psychopathological traits. The effects of the therapy on brain connectivity will also be analyzed using fMRI, and on pain neurophysiology through the Conditioned Pain Modulation (CPM) paradigm. The protocol provides for the evaluation of therapy effectiveness at three follow-ups (3, 6, and 12 months) in order to measure the duration of effects.

Finally, through advanced statistical analysis tools and the support of artificial intelligence, the study also aims to identify specific clinical-neurofunctional profiles that may be useful for differential diagnosis and for tailoring therapeutic interventions.

Detailed Description

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Conditions

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Chronic Primary Orofacial Pain (CPOP) Persistent Idiopathic Facial Pain (PIFP)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PRT-TAU

Patients will attend 8 sessions of PRT treatments while undergoing their usual pharmacological treatment

Group Type EXPERIMENTAL

Pain Reprocessing Therapy

Intervention Type BEHAVIORAL

One cohort of 30 patients (PRT+TAU group) will receive eight sessions of Pain Reprocessing Therapy (PRT) in addition to Treatment-as-Usual (TAU). PRT is a cognitive-behavioral-inspired approach aimed at helping patients reinterpret chronic pain as brain-generated rather than structurally caused.

A second cohort of 30 patients (TAU group) will undergo the same assessment phases but will receive only Treatment-as-Usual without PRT.

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TAU

Patients will undergo the usual pharmacological treatment.

Group Type PLACEBO_COMPARATOR

Usual Therapy

Intervention Type BEHAVIORAL

Patients undergo yhe usual pharmacological tretment as prescrived by neurologist

Interventions

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Pain Reprocessing Therapy

One cohort of 30 patients (PRT+TAU group) will receive eight sessions of Pain Reprocessing Therapy (PRT) in addition to Treatment-as-Usual (TAU). PRT is a cognitive-behavioral-inspired approach aimed at helping patients reinterpret chronic pain as brain-generated rather than structurally caused.

A second cohort of 30 patients (TAU group) will undergo the same assessment phases but will receive only Treatment-as-Usual without PRT.

Use this module to add a description of each group or cohort in the study and to list any interventions of interest.

Intervention Type BEHAVIORAL

Usual Therapy

Patients undergo yhe usual pharmacological tretment as prescrived by neurologist

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of Chronic Primary Orofacial Pain (CPOP) according to ICD-11 criteria.
* Written informed consent.
* Age 18 years or older.

Exclusion Criteria

* Age over 70 years.
* Current use of immunosuppressive medications (e.g., steroids).
* History of cancer (breast, thyroid, prostate, blood cancers, etc.).
* History of stroke, neurosurgical interventions, or brain tumors.
* History of specific inflammatory diseases (lupus, scleroderma, rheumatoid arthritis, polymyalgia rheumatica).
* History of psychiatric disorders such as schizophrenia, personality disorders, dissociative identity disorder, or other severe psychoses.
* Unexpected or unintentional weight loss of 10 kg or more in the year prior to recruitment.
* Difficulty participating due to logistical problems.
* Contraindications to undergoing functional magnetic resonance imaging (fMRI).
* Psychotherapy treatment of any kind within 15 months prior to the assessment date.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Licia Grazzi, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Neurologico Carlo Besta

Locations

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Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Licia Grazzi, MD

Role: CONTACT

+ 39 02.2394

Alessandra Telesca, phd

Role: CONTACT

Facility Contacts

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Licia Grazzi, MD

Role: primary

+ 39 02.2394

Alessandra Telesca, PHD

Role: backup

0039.02.2394

References

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Schmidt S, Muhlan H, Power M. The EUROHIS-QOL 8-item index: psychometric results of a cross-cultural field study. Eur J Public Health. 2006 Aug;16(4):420-8. doi: 10.1093/eurpub/cki155. Epub 2005 Sep 1.

Reference Type BACKGROUND
PMID: 16141303 (View on PubMed)

Monticone M, Baiardi P, Ferrari S, Foti C, Mugnai R, Pillastrini P, Rocca B, Vanti C. Development of the Italian version of the Pain Catastrophising Scale (PCS-I): cross-cultural adaptation, factor analysis, reliability, validity and sensitivity to change. Qual Life Res. 2012 Aug;21(6):1045-50. doi: 10.1007/s11136-011-0007-4. Epub 2011 Sep 13.

Reference Type BACKGROUND
PMID: 21912846 (View on PubMed)

Benoliel R, Svensson P, Evers S, Wang SJ, Barke A, Korwisi B, Rief W, Treede RD; IASP Taskforce for the Classification of Chronic Pain. The IASP classification of chronic pain for ICD-11: chronic secondary headache or orofacial pain. Pain. 2019 Jan;160(1):60-68. doi: 10.1097/j.pain.0000000000001435.

Reference Type BACKGROUND
PMID: 30586072 (View on PubMed)

Robson WL, Leung AK, Kabani AM, Fick GH. Pseudohyperkalaemia in Kawasaki disease. Eur J Pediatr. 1993 Apr;152(4):379-80. doi: 10.1007/BF01956763. No abstract available.

Reference Type BACKGROUND
PMID: 8482298 (View on PubMed)

Benoliel R, Gaul C. Persistent idiopathic facial pain. Cephalalgia. 2017 Jun;37(7):680-691. doi: 10.1177/0333102417706349. Epub 2017 Apr 20.

Reference Type BACKGROUND
PMID: 28425324 (View on PubMed)

Nicholas M, Vlaeyen JWS, Rief W, Barke A, Aziz Q, Benoliel R, Cohen M, Evers S, Giamberardino MA, Goebel A, Korwisi B, Perrot S, Svensson P, Wang SJ, Treede RD; IASP Taskforce for the Classification of Chronic Pain. The IASP classification of chronic pain for ICD-11: chronic primary pain. Pain. 2019 Jan;160(1):28-37. doi: 10.1097/j.pain.0000000000001390.

Reference Type BACKGROUND
PMID: 30586068 (View on PubMed)

Other Identifiers

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GR2024

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

FACE-PRT

Identifier Type: -

Identifier Source: org_study_id

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