The Use of tDCS in the Orofacial Pain

Study Overview
=================
Brief Summary
-----------------
The trial´s main goal is to explore the use of transcranial direct current stimulation (tDCS) as a treatment option for persons suffering from orofacial pain. The aim of the trial is to further investigate the efficacy and longevity of tDCS in treating chronic pharmacoresistant orofacial pain. A prospective, randomized, double-blinded, two-arm, sham-controlled design will be utilized. Primarily, the analgesic effect's intensity and duration will be assessed. Secondarily, the associated reduction of symptoms of anxiety and depression will be investigated, as well as the impact on the general quality of life. Anodal stimulation (6 sessions in 2 weeks, 2mA, 20 min, cathode over the opposite Fp area) of M1 contralateral to the pain location will be employed. Washout periods of 48-72 hours will be kept between applications to improve neuroplasticity changes' induction, which is estimated to reflect in the effect retention. Eight major evaluation points will be employed in 26 weeks, and a daily numeric rating scale (NRS) self-assessment. The trial will potentially improve the quality of life, reduce the health burden caused by chronic orofacial pain, and provide further data on the use of tDCS in this setting, thus, enabling an additional route to manage the symptoms of pain in the future.

Official Title
-----------------
The Application of New Diagnostic (Thermovision) and Treatment (tDCS) Procedures in Patients With Drug-resistant Orofacial Pain

Conditions
-----------------
Orofacial Pain

Intervention / Treatment
-----------------
* Device: Transcranial Direct Current Stimulation
* Device: Sham Transcranial Direct Current Stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of Orofacial Pain by a pain medicine specialist according to ICOP (International classification of orofacial pain) and ICHD3 (International classification of headache disorder) Stable analgesic therapy one month before the stimulation series Exclusion Criteria: Changes to the analgesic therapy in 6 months following the stimulation series Non-compliance with the follow-ups General contraindications to tDCS - pregnancy, unstable cardiovascular disorders, epilepsy and intracranial masses

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, randomized, double-blinded, placebo-controlled, two-arm trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active group<br>The investigators aim for six sessions of anodal stimulation over the right primary motor area contralateral to the orofacial pain (C3 or C4 in 10-20 EEG system) with cathode above the frontal area ipsilateral to the orofacial pain (Fp1 or Fp2) using HDCstim by Newronika S.r.l., Italy. The therapy will be administered over two weeks (Mon, Wed, Fri) to ensure a washout period of 48 to 72 hours between applications. The current of 2 mA will be delivered via silicone electrodes inserted into saline (0.9%) filled cellulose sponges, anode 5x5cm, cathode 6x8cm, for 20 minutes with 20 seconds of both ramp-up and ramp-down. An International 10-20 EEG system will be used to determine the stimulation location, and dedicated EEG caps will be used to ensure consistency between applications. | Device: Transcranial Direct Current Stimulation<br>* Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulatory method utilizing weak electrical currents to elicit short and long-term central nervous system changes.<br>* Other names: tDCS;|
| Placebo Comparator: Sham group<br>The sham (placebo) will be administered using the same devices with a preprogrammed sham protocol (using HDCprog by Newronika S.r.l., Italy) of 20 minutes to be virtually indistinguishable from the active stimulation. | Device: Sham Transcranial Direct Current Stimulation<br>* The sham was administered using the same tDCS devices as in the active group with a preprogrammed sham protocol of 20 minutes to be virtually indistinguishable from the active stimulation.<br>* Other names: Sham tDCS;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The McGill Pain Questionnaire (short form). | The Short-form McGill Pain Questionnaire is a standardized questionnaire assessing pain's sensory and affective dimensions. The types of pain are scaled as to their intensity between 1-4 (a higher value denotes higher intensity), the overall intensity is scaled between 0-5 (a higher value denotes higher intensity), and VAS is used to visualize the notion of pain (evaluated on a scale of 0-10, a higher value denotes higher intensity). | The measurement will be established as a baseline prior to the stimulation series. (at T1) | 
| Changes in The McGill Pain Questionnaire (short form) at T2. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T2 (after the 6th stimulation, 2 weeks since T1) | 
| Changes in The McGill Pain Questionnaire (short form) at T3. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T3 (6 weeks since T1) | 
| Changes in The McGill Pain Questionnaire (short form) at T4. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T4 (10 weeks since T1) | 
| Changes in The McGill Pain Questionnaire (short form) at T5. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T5 (14 weeks since T1) | 
| Changes in The McGill Pain Questionnaire (short form) at T6. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T6 (18 weeks since T1) | 
| Changes in The McGill Pain Questionnaire (short form) at T7. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T7 (22 weeks since T1) | 
| Changes in The McGill Pain Questionnaire (short form) at T8. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T8 (26 weeks since T1) | 
| The numeric rating scale (NRS) as part of pain diary | The numeric rating scale (NRS) is 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. | The measurement will be established as a baseline prior to the stimulation series. (at T1) | 
| Changes in the numeric rating scale (NRS) every day of them follow-up period. | The numeric rating scale (NRS) is 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. | Measured every day since T1 up until T8. (for 26 weeks in total) | 
| The Margolis Pain Diagram | The Margolis pain diagram weights the extension and distribution of pain, expressed as the percentage of body surface in pain and its location. The tool consists of a dorsal and a ventral drawing of the body. The subjects are asked to shade areas in which they have experienced pain. | The measurement will be established as a baseline prior to the stimulation series. (at T1) | 
| Changes in the Margolis Pain Diagram at T2. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T2 (after the 6th stimulation, 2 weeks since T1) | 
| Changes in the Margolis Pain Diagram at T3. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T3 (6 weeks since T1) | 
| Changes in the Margolis Pain Diagram at T4. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T4 (10 weeks since T1) | 
| Changes in the Margolis Pain Diagram at T5. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T5 (14 weeks since T1) | 
| Changes in the Margolis Pain Diagram at T6. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T6 (18 weeks since T1) | 
| Changes in the Margolis Pain Diagram at T7. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T7 (22 weeks since T1) | 
| Changes in the Margolis Pain Diagram at T8. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T8 (26 weeks since T1) | 
| The questionnaire of interference with daily activities | A standardized questionnaire to evaluate the interference of pain with daily activities. Minimum=0 points, maximum=5 points. A higher score generally means more severe interference. | The measurement will be established as a baseline prior to the stimulation series. (at T1) | 
| Changes in the questionnaire of interference with daily activities at T2. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T2 (after the 6th stimulation, 2 weeks since T1) | 
| Changes in the questionnaire of interference with daily activities at T3. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T3 (6 weeks since T1) | 
| Changes in the questionnaire of interference with daily activities at T4. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T4 (10 weeks since T1) | 
| Changes in the questionnaire of interference with daily activities at T5. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T5 (14 weeks since T1) | 
| Changes in the questionnaire of interference with daily activities at T6. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T6 (18 weeks since T1) | 
| Changes in the questionnaire of interference with daily activities at T7. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T7 (22 weeks since T1) | 
| Changes in the questionnaire of interference with daily activities at T8. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T8 (26 weeks since T1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beck's Depression Inventory (BDI) | A standardized questionnaire to evaluate the symptoms of depression. Minimum=0 points, maximum=63 points. A higher score generally means more severe anxiety | The measurement will be established as a baseline prior to the stimulation series. (at T1) | 
| Changes in Beck's Depression Inventory (BDI) at T2. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T2 (after the 6th stimulation, 2 weeks since T1) | 
| Changes in Beck's Depression Inventory (BDI) at T3. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T3 (6 weeks since T1) | 
| Changes in Beck's Depression Inventory (BDI) at T4. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T4 (10 weeks since T1) | 
| Changes in Beck's Depression Inventory (BDI) at T5. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T5 (14 weeks since T1) | 
| Changes in Beck's Depression Inventory (BDI) at T6. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T6 (18 weeks since T1) | 
| Changes in Beck's Depression Inventory (BDI) at T7. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T7 (22 weeks since T1) | 
| Changes in Beck's Depression Inventory (BDI) at T8. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T8 (26 weeks since T1) | 
| Beck Anxiety Inventory (BAI) | A standardized questionnaire to evaluate the symptoms of anxiety. Minimum=0 points, maximum=63 points. A higher score generally means more severe anxiety | The measurement will be established as a baseline prior to the stimulation series. (at T1) | 
| Changes in Beck Anxiety Inventory (BAI) at T2. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T2 (after the 6th stimulation, 2 weeks since T1) | 
| Changes in Beck Anxiety Inventory (BAI) at T3. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T3 (6 weeks since T1) | 
| Changes in Beck Anxiety Inventory (BAI) at T4. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T4 (10 weeks since T1) | 
| Changes in Beck Anxiety Inventory (BAI) at T5. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T5 (14 weeks since T1) | 
| Changes in Beck Anxiety Inventory (BAI) at T6. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T6 (18 weeks since T1) | 
| Changes in Beck Anxiety Inventory (BAI) at T7. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T7 (22 weeks since T1) | 
| Changes in Beck Anxiety Inventory (BAI) at T8. | Changes compared to the baseline (T1) will be calculated and further statistically compared between the groups. A negative difference to the baseline means an improvement | Measured at T8 (26 weeks since T1) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Orofacial Pain, tDCS, trancranial DIrect Current Stimulation, NIBS, non-invasive brain stimulation