Effect of Hypnosis Combined With Tdcs on Pain Perception and Cortical Excitability in Fibromyalgia

Study Overview
=================
Brief Summary
-----------------
Fibromyalgia is a public health condition, which causes great functional disability. Conventional treatment modalities have been shown a very poor therapeutic response, in that most individuals end up becoming poly-medicated and refractory to treatment. Non-pharmacological techniques with promising effects on the syndrome symptoms include both hypnotic analgesia and the transcranial direct-current stimulation (tDCS). Giving the treatment limitations of this syndrome its important to better understand the pain processess in fibromyalgia and treatments effect. This project was developed in order to evaluate the synergistic effect of a hypnotic analgesia suggestion associated with tDCS over pain levels and cortical excitability in individuals with fibromyalgia over a nociceptive stimulation pattern.

Detailed Description
-----------------
Fibromyalgia is a public health condition, which causes great functional disability. Its consequences pervade the personal and social life of the patient, leading to significant impairments in their interpersonal relationships, including work, family and social spheres. The symptoms affect both the physical and emotional abilities. Conventional treatment modalities have been shown a very poor therapeutic response, in that most individuals end up becoming poly-medicated and refractory to treatment. Non-pharmacological techniques with promising effects on the syndrome symptoms include both hypnotic analgesia and the transcranial direct-current stimulation (tDCS). Giving the treatment limitations of this syndrome its important to better understand the pain processess in fibromyalgia and treatments effect. This project was developed in order to evaluate the synergistic effect of a hypnotic analgesia suggestion associated with tDCS over pain levels and cortical excitability in individuals with fibromyalgia over a nociceptive stimulation pattern. It will be performed as a blinded sham controlled cross-over randomized clinical trial. It will be included 20 female subjects diagnosed with fibromyalgia, according to the 2016 revision of the American College of Rheumatologycriteria (2010;2011), ranging in age from 18 to 65 years old, highly susceptible to the hypnosis technique (score ≥ 8) according to the Waterloo-Stanford Scale of Hypnotic Susceptibility (WSGC). They will be allocated in one of two groups, receiving with each cross-over one of the following interventions: A (active-tDCS), B (hypnotic analgesia suggestion), C (Rest), D (active-tDCS + hypnotic analgesia suggestion) and E (sham-tDCS + hypnotic analgesia suggestion). The primary endpoints will be the level of pain, measured by a numerical pain scale (NPS), during nociceptive stimuli induced by the cold pressor test and Short Intracortical Inhibition (SICI). The secondary endpoints will be descent pain modulation system power through the Conditioned Pain Modulation test (CPM - task); and the cortical excitability assessed by Motor Threshold (MT), Motor Evoked Potential (MEP), Cortical Silent Period (CSP) and Short Intracortical Facilitation (SICF) tests during Transcranial Magnetic Stimulation (TMS). The intra and inter-group comparisons will be made by means of two-way ANOVA followed by Bonferroni. A type I error of 5% and type II error of 20%. The present study hypothesizes a synergistic effect of both interventions on pain intensity reported on the Cold Pressor Test, as well as the reduction in the inhibition of cortical excitability level assessed by the TMS, compared to the same measures in an isolated manner.

Official Title
-----------------
Effect of Hypnosis Combined With Transcranial Direct Current Stimulation on Pain Perception and Cortical Excitability in Fibromyalgia: A Blinded Randomized Crossover Sham Controlled Clinical Trial

Conditions
-----------------
Transcranial Direct Current Stimulation, Hypnosis, Fibromyalgia

Intervention / Treatment
-----------------
* Device: Active Tracranial Direct Current Stimulation
* Other: Hypnotic analgesia suggestion
* Behavioral: Rest
* Other: Active tDCS + Hypnotic analgesia suggestion
* Other: Sham tDCS + Hypnotic analgesia suggestion


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women Literate Fibromyalgia diagnosis according to 2016 American College of Rheumatology criteria Pain score ≥ 6 in the Numerical Pain Scale during most of the time in the last 3 months. Score ≥ 8 /12 in the Waterloo-Stanford Group Hypnotic Susceptibility Scale C Exclusion Criteria: Contraindication to Transcranial Magnetic Stimulation Metallic implant in brain Medical implants in brain Cardiac Pacemaker Cochlear implant History of drug or alcohol abuse in the last 6 months Neurological disorders History of head trauma or neurosurgery Decompensated systemic diseases Chronic inflammatory diseases (lupus, rheumatoid arthritis, Sjogren syndrome, Reiter syndrome) Decompensated hypothyroidism History of cancer

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

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

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

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Design: Randomized blinded factorial sham controlled clinical trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sequence of interventions starting with tDCS as the first intervention<br>Week 1 Active tDCS left dorso-lateral prefrontal cortex. F3 anode F4 catode Area of electrodes: 35 cm2 Current intensity: 2mA Stimulation Time: 20min Week 2 Rest The subjects will be asked to remain seated and still for 20 minutes. Week 3 Hypnotic analgesia suggestion Classic approach. The intervention starts with a induction with suggestions for the subject to focus her attention in a single stimuli, combined with progressive relaxation. After that, direct suggestions are given for comfort and pain reduction. Intervention time: 20 minutes Week 4 Active tDCS + Hypnotic analgesia suggestion Intervention Time: 20 minutes. Week 5 Sham tDCS + Hypnotic analgesia suggestion The sham tDCS will have the same areas of stimulation of the active tDCS, but the device will turn itself out after 30 seconds. Intervention time: 20 minutes | Device: Active Tracranial Direct Current Stimulation<br>* Site: dorsolateral prefrontal cortex. F3 anode and F4 catode. Electrode area: 35cm2 Current Intensity: 2mA Stimulation time: 20 min The current ramps up during 30 seconds reaching 2mA, staying this way until the last 30 seconds of stimulation, in wich the current slowly decreases to zero.<br>* Other names: a-tDCS;Other: Hypnotic analgesia suggestion<br>* The hypnotic induction protocol was standardized to be applied equally to all subjects. The protocol for hypnotic analgesia begins with an induction with a sequence of suggestions for the subjects to focus their attention on an individual stimulus, associated with progressive relaxation. After that, direct suggestions are given for comfort and pain reduction. The intervention lasts 20 minutes, with 12 minutes of induction and 8 minutes of hypnotic suggestions to reduce pain and leave the trance.<br>* Other names: Hypnosis;Behavioral: Rest<br>* The patient is asked to remain seated still for 20 minutes.<br>Other: Active tDCS + Hypnotic analgesia suggestion<br>* Site: dorsolateral prefrontal cortex. F3 anode and F4 catode. Electrode area: 35cm2 Current Intensity: 2mA Intervention time: 20 min The current ramps up during 30 seconds reaching 2mA, staying this way until the last 30 seconds of stimulation, in wich the current slowly decreases to zero. The hypnotic induction protocol was standardized to be applied equally to all subjects. The protocol for hypnotic analgesia begins with an induction with a sequence of suggestions for the subjects to focus their attention on an individual stimulus, associated with progressive relaxation. After that, direct suggestions are given for comfort and pain reduction. The intervention lasts 20 minutes, with 12 minutes of induction and 8 minutes of hypnotic suggestions to reduce pain and leave the trance.<br>* Other names: a-tDCS+HS;Other: Sham tDCS + Hypnotic analgesia suggestion<br>* Site: dorsolateral prefrontal cortex. F3 anode and F4 catode. Electrode area: 35cm2 Current Intensity: 0mA Intervention time: 20 min The current is turned off after 30 seconds. The hypnotic induction protocol was standardized to be applied equally to all subjects. The protocol for hypnotic analgesia begins with an induction with a sequence of suggestions for the subjects to focus their attention on an individual stimulus, associated with progressive relaxation. After that, direct suggestions are given for comfort and pain reduction. The intervention lasts 20 minutes, with 12 minutes of induction and 8 minutes of hypnotic suggestions to reduce pain and leave the trance.<br>* Other names: s-tDCS+HS;|
| Other: Sequence of interventions starting with Hypnosis as the first intervention<br>Week 1 Hypnotic analgesia suggestion Classic approach. The intervention starts with a induction with suggestions for the subject to focus her attention in a single stimuli, combined with progressive relaxation. After that, direct suggestions are given for comfort and pain reduction. Intervention time: 20 minutes Week 2 Rest The subjects will be asked to remain seated and still for 20 minutes. Week 3 Active tDCS left dorso-lateral prefrontal cortex. F3 anode F4 catode Area of electrodes: 35 cm2 Current intensity: 2mA Stimulation Time: 20min Week 4 Sham tDCS + Hypnotic analgesia suggestion The sham tDCS will have the same areas of stimulation of the active tDCS, but the device will turn itself out after 30 seconds. Intervention time: 20 minutes Week 5 Active tDCS + Hypnotic analgesia suggestion Intervention Time: 20 minutes. | Device: Active Tracranial Direct Current Stimulation<br>* Site: dorsolateral prefrontal cortex. F3 anode and F4 catode. Electrode area: 35cm2 Current Intensity: 2mA Stimulation time: 20 min The current ramps up during 30 seconds reaching 2mA, staying this way until the last 30 seconds of stimulation, in wich the current slowly decreases to zero.<br>* Other names: a-tDCS;Other: Hypnotic analgesia suggestion<br>* The hypnotic induction protocol was standardized to be applied equally to all subjects. The protocol for hypnotic analgesia begins with an induction with a sequence of suggestions for the subjects to focus their attention on an individual stimulus, associated with progressive relaxation. After that, direct suggestions are given for comfort and pain reduction. The intervention lasts 20 minutes, with 12 minutes of induction and 8 minutes of hypnotic suggestions to reduce pain and leave the trance.<br>* Other names: Hypnosis;Behavioral: Rest<br>* The patient is asked to remain seated still for 20 minutes.<br>Other: Active tDCS + Hypnotic analgesia suggestion<br>* Site: dorsolateral prefrontal cortex. F3 anode and F4 catode. Electrode area: 35cm2 Current Intensity: 2mA Intervention time: 20 min The current ramps up during 30 seconds reaching 2mA, staying this way until the last 30 seconds of stimulation, in wich the current slowly decreases to zero. The hypnotic induction protocol was standardized to be applied equally to all subjects. The protocol for hypnotic analgesia begins with an induction with a sequence of suggestions for the subjects to focus their attention on an individual stimulus, associated with progressive relaxation. After that, direct suggestions are given for comfort and pain reduction. The intervention lasts 20 minutes, with 12 minutes of induction and 8 minutes of hypnotic suggestions to reduce pain and leave the trance.<br>* Other names: a-tDCS+HS;Other: Sham tDCS + Hypnotic analgesia suggestion<br>* Site: dorsolateral prefrontal cortex. F3 anode and F4 catode. Electrode area: 35cm2 Current Intensity: 0mA Intervention time: 20 min The current is turned off after 30 seconds. The hypnotic induction protocol was standardized to be applied equally to all subjects. The protocol for hypnotic analgesia begins with an induction with a sequence of suggestions for the subjects to focus their attention on an individual stimulus, associated with progressive relaxation. After that, direct suggestions are given for comfort and pain reduction. The intervention lasts 20 minutes, with 12 minutes of induction and 8 minutes of hypnotic suggestions to reduce pain and leave the trance.<br>* Other names: s-tDCS+HS;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Pain Levels during Cold Pressor Test from Pre to Post Interventions | Pain levels measured by a numerical visual analogue scale during Cold Pressor Test. The subject will have her hand submerged in cold water at 0 degrees celcius up to 2 minutes. | First assessed 40 minutes Pre interventions and 70 minutes post interventions | 
| Changes in Pain Tolerance during Cold Pressor Test from Pre to Post Interventions | The time in the subject withstands with his hand submerged in cold water at 0 degrees celcius during Cold Pressor Test. With a maximum of 2 minutes. | First assessed 40 minutes Pre interventions and again 70 minutes post interventions | 
| Changes in Short Cortical Inhibition during Transcranial Magnetic Stimulation from pre to post interventions | Short Cortical Inhibition measured by Transcranial Magnetic Stimulation. Using the MagOption for MagPro R30 and X100 device with electromyography. | First assessed 10 minutes Pre intervention and again 20 minutes post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Numerical Pain Scale during Conditioned Pain Modulation-task from Pre to Post Interventions | Descending pain modulation system assessed by Conditioned Pain Modulation task. The subject will be asked to put her non-dominant hand in a bucket with cold water at 0 degrees celsius. The other forearm will receive a painful heat stimuli using a device. The CPM score is calculated using the difference between the mean pain of both arms during the outcome assessment. | First assessed 50 minutes pre interventions and again 1 hour post interventions | 
| Changes in Motor Threshold from Pre to Post Interventions | Motor Threshold assessed by Transcranial Magnetic Stimulation | First assessed 30 minutes Pre interventions and again immediately post interventions | 
| Changes in Motor Evoked Potential from Pre to Post Interventions | Motor Evoked Potential assessed by Transcranial Magnetic Stimulation | First assessed 25 minutes Pre interventions and again 5 minutes post interventions | 
| Changes in Silent Period from Pre to Post Interventions | Silent Period assessed by Transcranial Magnetic Stimulation | First assessed 5 minutes Pre Interventions and again 25 minutes post interventions | 
| Changes in Intra-cortical Facilitation from Pre to Post Interventions | Intra-cortical Facilitation assessed by Transcranial Magnetic Stimulation | First assessed 10 minutes Pre intervention and again 20 minutes post intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
chronic pain, fibromyalgia, hypnotic analgesia, tDCS, DPMS, Cold pressor test