Chronic Primary Orofacial Pain (CPOP)FACE-PRTNCT07123233
An Innovative Cognitive-Behavioral Treatment For Chronic Orofacial Pain
A study testing Pain Reprocessing Therapy and Usual Therapy in people with Chronic Primary Orofacial Pain (CPOP) and Persistent Idiopathic Facial Pain (PIFP), run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 1 site in Italy.
Trial summary
Use these resources to provide understandable information about this study to patients, families, and health care providers: 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Primary Orofacial Pain (CPOP), Persistent Idiopathic Facial Pain (PIFP)
- What is being tested?
- Pain Reprocessing Therapy and Usual Therapy
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteItaly
- Study dates
- 24 Sep 2025to May 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of Chronic Primary Orofacial Pain (CPOP) according to ICD-11 criteria.
- Patient-reported pain rating of 4 or higher out of 10 on the Brief Pain Inventory (BPI) question assessing average pain over the past week, consistent with inclusion criteria from previous chronic pain studies.
- Written informed consent.
- Age 18 years or older.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Alessandra Telesca, phd contact
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, 20133
Licia Grazzi, MD, + 39 02.2394, licia.grazzi@istituto-besta.it
Alessandra Telesca, PHD, 0039.02.2394, alessandra.telesca@istituto-besta.it
About this study
Official title: Reprocessing The Fear Of Pain - A Cognitive-Behavioral Protocol For Chronic Primary Orofacial Pain Diseases.
Use these resources to provide understandable information about this study to patients, families, and health care providers:
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.
Read more
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.
- Being tested
- Pain Reprocessing Therapy, Usual Therapy
- Keywords
- Cognitive-behavioral therapy, Pain-Reprocessing Therapy, Chronic Primary Orofacial pain, chronic pain, chronic primary pain, nociplastic pain
- Medical subject headings
- Chronic Pain, Nociplastic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pain Reprocessing TherapyBehavioural
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.
Usual TherapyBehavioural
Patients undergo yhe usual pharmacological tretment as prescrived by neurologist
| Study group | Role | What they receive |
|---|---|---|
| PRT-TAU | Experimental | Patients will attend 8 sessions of PRT treatments while undergoing their usual pharmacological treatment Receives: Behavioral: Pain Reprocessing Therapy |
| TAU | Placebo comparator | Patients will undergo the usual pharmacological treatment. Receives: Behavioral: Usual Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average pain intensity over the past week.
Average pain intensity over the past week, measured using the Brief Pain Inventory-Short Form (BPI-SF). Score range: 0-10, with higher scores indicating greater pain intensity (worse outcome).
Measured: 12 months
Secondary outcomes (4)
Quality of life (EUROHIS-8)
It includes 8 items scored from 1 to 5 using a 5-point Likert scale investigating the satisfaction on different life domains (i.e., socio-economic conditions, health conditions, satisfaction with oneself and with one's relationships, etc.). A high total score corresponds to a high perception of quality of life.
Measured: 12 months
Depressive and anxiety symptoms (BDI-II, BAI)
BDI-II - It consists of 21 items, each scored on a 4-point Likert scale (ranging from 0 to 3). A score above 13 points indicates the presence of clinical depression symptoms. BAI - It consists of 21 items, each scored on a 4-point Likert scale (ranging from 0 to 3). A score above 7 points indicates the presence of clinical anxiety symptoms.
Measured: 12 months
Catastrophism (PCS)
it measures feelings of helplessness, magnification, and rumination. It has 13 items, each reflecting different aspects of catastrophic thinking related to pain. Respondents rate each item on a 5-point Likert scale, ranging from 0 (not at all) to 4 (extremely), based on how frequently they experience the thought or feeling described. Higher scores indicate greater levels of pain catastrophizing.
Measured: 12 months
Psychopathology (MCMI-III)
It is a validated self-administered inventory with 175 true-false questions, assessing 14 personality disorder scales, divided into fourteen clinical patterns of personality based on Axis II disorders of DSM-IV, and ten clinical syndrome scales based on Axis I disorders of DSM-IV.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2025
- Study start24 Sep 2025
- Primary completionMay 2028 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Chronic Primary Orofacial Pain (CPOP)Studies of the same condition, open and under way.
- More trials run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Licia Grazzi, MD, Principal investigator, Fondazione IRCCS Istituto Neurologico Carlo Besta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07123233
- Sponsor's protocol ID
- FACE-PRT
- Other IDs
- GR2024
- Acronym
- FACE-PRT
- Status last verified
- Nov 2026
- First submitted
- 7 Aug 2025
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 16141303Monticone 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.
PubMed 21912846Benoliel 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.
PubMed 30586072Ashar YK, Gordon A, Schubiner H, Uipi C, Knight K, Anderson Z, Carlisle J, Polisky L, Geuter S, Flood TF, Kragel PA, Dimidjian S, Lumley MA, Wager TD. Effect of Pain Reprocessing Therapy vs Placebo and Usual Care for Patients With Chronic Back Pain: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Jan 1;79(1):13-23. doi: 10.1001/jamapsychiatry.2021.2669.
PubMed 34586357Benoliel R, Gaul C. Persistent idiopathic facial pain. Cephalalgia. 2017 Jun;37(7):680-691. doi: 10.1177/0333102417706349. Epub 2017 Apr 20.
PubMed 28425324Nicholas 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.
PubMed 30586068
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reprocessing The Fear Of Pain - A Cognitive-Behavioral Protocol For Chronic Primary Orofacial Pain Diseases.
- ClinicalTrials.gov ID
- NCT07123233
- Acronym / sponsor ID
- FACE-PRT / FACE-PRT
- Keywords
- Cognitive-behavioral therapy, Pain-Reprocessing Therapy, Chronic Primary Orofacial pain, chronic pain, chronic primary pain, nociplastic pain
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Fondazione I.R.C.C.S. Istituto Neurologico Carlo BestaUniversity, hospital or other
- Study start
- 24 Sep 2025 (actual)
- Primary completion
- May 2028 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 14 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Use these resources to provide understandable information about this study to patients, families, and health care providers:
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PRT-TAU | Experimental | Behavioral: Pain Reprocessing TherapyPatients will attend 8 sessions of PRT treatments while undergoing their usual pharmacological treatment |
| TAU | Placebo comparator | Behavioral: Usual TherapyPatients will undergo the usual pharmacological treatment. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of Chronic Primary Orofacial Pain (CPOP) according to ICD-11 criteria.
- Patient-reported pain rating of 4 or higher out of 10 on the Brief Pain Inventory (BPI) question assessing average pain over the past week, consistent with inclusion criteria from previous chronic pain studies.
- Written informed consent.
- Age 18 years or older.
Key exclusion criteria (10 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pain Reprocessing TherapyOne 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. | Behavioural | PRT-TAU |
| Usual TherapyPatients undergo yhe usual pharmacological tretment as prescrived by neurologist | Behavioural | TAU |
Primary outcome
Average pain intensity over the past week.
Time frame: 12 months
Average pain intensity over the past week, measured using the Brief Pain Inventory-Short Form (BPI-SF). Score range: 0-10, with higher scores indicating greater pain intensity (worse outcome).
4 secondary outcomes
Quality of life (EUROHIS-8)
Time frame: 12 months
Depressive and anxiety symptoms (BDI-II, BAI)
Time frame: 12 months
Catastrophism (PCS)
Time frame: 12 months
Psychopathology (MCMI-III)
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Background: PubMed 16141303Schmidt 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.
- Background: PubMed 21912846Monticone 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.
- Background: PubMed 30586072Benoliel 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.
- Background: PubMed 34586357Ashar YK, Gordon A, Schubiner H, Uipi C, Knight K, Anderson Z, Carlisle J, Polisky L, Geuter S, Flood TF, Kragel PA, Dimidjian S, Lumley MA, Wager TD. Effect of Pain Reprocessing Therapy vs Placebo and Usual Care for Patients With Chronic Back Pain: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Jan 1;79(1):13-23. doi: 10.1001/jamapsychiatry.2021.2669.
- Background: PubMed 28425324Benoliel R, Gaul C. Persistent idiopathic facial pain. Cephalalgia. 2017 Jun;37(7):680-691. doi: 10.1177/0333102417706349. Epub 2017 Apr 20.
- Background: PubMed 30586068Nicholas 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alessandra Telesca, phd contact
Licia Grazzi, MD principal investigator
Fondazione IRCCS Istituto Neurologico Carlo Besta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pain Reprocessing Therapy and Usual Therapy in people with Chronic Primary Orofacial Pain (CPOP) and Persistent Idiopathic Facial Pain (PIFP), run by Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Licia Grazzi, MD (+ 39 02.2394, licia.grazzi@istituto-besta.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average pain intensity over the past week. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07123233, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.