Study of the Synergistic Effects of Biofeedback and Transcranial Electrical Stimulation in Anxio-depressive Disorders

Study Overview
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Brief Summary
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Anxio-depressive disorders are characterized by a difficulty in regulating the negative or aversive emotions adequately. These dysfunctions have been linked to a deficit in prefrontal cortex activity. The latter has an inhibitory influence on limbic regions -especially the amygdala- involved in the generation of emotions. By this means, the prefrontal cortex intervenes in the control of the sympathetic and parasympathetic branches of the autonomic nervous system whp are responsible for the physiological components of the emotion, including the variations of the cardiac rhythm (HRV: heart rate variability). In emotionally demanding situations, the activity of the prefrontal cortex is generally associated with an increase in parasympathetic activity that is exerted by stimulation of the vagus nerve. In patients with anxio-depressive disorder, there is a decrease in the activity of the autonomic nervous system whose variability in heart rate is a recognized marker. Many studies show a beneficial impact of transcranial direct current stimulation (t-DCS) on anxio-depressive symptoms, particularly when a particular area is targeted: the dorso-lateral prefrontal cortex. The impacts of this intervention are multiple and aim in particular to modulate the activity of the autonomic nervous system to promote regulation. Biofeedback HRV is a technique that allows you to learn how to modulate your heart rate by means of respiratory control exercises. The patient receives an immediate feedback on the effectiveness of his learning (basic principle of bio-feedback). This intervention will allow to act on the parasympathetic activity and to promote a vagal tone adequate to the emotional regulation. Numerous studies have demonstrated the favorable impact of HRV biofeedback on the reduction of anxious and depressive symptoms. Since the vagus nerve seems to be a primary pathway in physiologically emotional regulation, and considering that vagal tone can be stimulated by both the activity of the prefrontal cortex and through respiratory control, it appears interesting to study the association of t-DCS with HRV biofeedback techniques. The first objective of this study is to show that HRV biofeedback training coupled with t-DCS is associated with a greater decrease in anxious symptomatology. The secondary objective of the study is to show that a coupling of these two techniques is associated with an increase of the variability of the cardiac rhythm as well as a more important decrease of the depressive symptomatology.

Official Title
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Study of the Synergistic Effects of Biofeedback and Transcranial Electrical Stimulation in Anxio-depressive Disorders

Conditions
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Anxiety Depression

Intervention / Treatment
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* Device: Transcranial direct current stimulation (t-DCS) device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnose of anxio-depressive disorder Good understanding of French High anxiety level (STAI questionnaire score higher to 46) with reported difficulties to manage this anxiety. Exclusion Criteria: Alcohol dependence (assessed by the AUDIT questionnaire) Pregnancy t-DCS contra indications : traumatic brain injury, epilepsy, known bipolar disease, electronic or metalic implant Known cardiac arrhythmia or intake of beta-blockers

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active t-DCS<br>Use of the t-DCS machine with the following stimulation parameters: current intensity of 2mA, electrode size of 25 cm2, duration of stimulation 20 minutes (excluding the fade-in and fade-out periods of 15 seconds). | Device: Transcranial direct current stimulation (t-DCS) device<br>* t-DCS is a brain electrostimulation technique that consists of applying a current of low intensity (between 1 and 2 mA) on the scalp via two electrodes, in order to modify the cerebral activity of the stimulated zones. The investigators use the Soterix Medical t-DCS devices of the mini-CT 1x1 type.<br>|
| Sham Comparator: Sham t-DCS<br>The condition of use in sham mode follows the same procedure as the active t-DCS except that the active stimulation lasts only 30 seconds at 3mA (60 seconds of active stimulation taking into account the periods of fade in and fade out). The stimulator remains switched on during the procedure but does not deliver current. The devices are fully automatic and deliver an active or sham current according to a randomized stimulation code whose meaning is unknown by the operator, in order to respect the triple blind. | Device: Transcranial direct current stimulation (t-DCS) device<br>* t-DCS is a brain electrostimulation technique that consists of applying a current of low intensity (between 1 and 2 mA) on the scalp via two electrodes, in order to modify the cerebral activity of the stimulated zones. The investigators use the Soterix Medical t-DCS devices of the mini-CT 1x1 type.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| State-trait anxiety inventory (STAI-Y) scores | Questionnaire with 20 questions, each with 4 possible answers. Each answer corresponds to a score of 1 to 4, 1 indicating the lowest degree of anxiety and 4 the highest degree. | Baseline (day 1) | 
| State-trait anxiety inventory (STAI-Y) scores | Questionnaire with 20 questions, each with 4 possible answers. Each answer corresponds to a score of 1 to 4, 1 indicating the lowest degree of anxiety and 4 the highest degree. | Day 8 | 
| State-trait anxiety inventory (STAI-Y) scores | Questionnaire with 20 questions, each with 4 possible answers. Each answer corresponds to a score of 1 to 4, 1 indicating the lowest degree of anxiety and 4 the highest degree. | Day 29 | 
| State-trait anxiety inventory (STAI-Y) scores | Questionnaire with 20 questions, each with 4 possible answers. Each answer corresponds to a score of 1 to 4, 1 indicating the lowest degree of anxiety and 4 the highest degree. | One time point between day 60 and day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Root mean square of successive differences (RMSSD) | The Root Mean Square of the Successive Differences (RMSSD) is one of a few time-domain tools used to assess heart rate variability, the successive differences being neighboring RR intervals. | Baseline (day 1) | 
| Root mean square of successive differences (RMSSD) | The Root Mean Square of the Successive Differences (RMSSD) is one of a few time-domain tools used to assess heart rate variability, the successive differences being neighboring RR intervals. | Day 8 | 
| Root mean square of successive differences (RMSSD) | The Root Mean Square of the Successive Differences (RMSSD) is one of a few time-domain tools used to assess heart rate variability, the successive differences being neighboring RR intervals. | Day 29 | 
| Root mean square of successive differences (RMSSD) | The Root Mean Square of the Successive Differences (RMSSD) is one of a few time-domain tools used to assess heart rate variability, the successive differences being neighboring RR intervals. | One time point between day 60 and day 90 | 
| High frequency in spectral analysis | Spectral analysis of the RR interval is an indirect, noninvasive measurement tool of heart rate variability. High-frequency RR signal (greater than 0.15 Hz) is associated with increased parasympathetic tone, and low-frequency RR signal (0.04-0.15 Hz) is associated with increased sympathetic tone. | Baseline (day 1) | 
| High frequency in spectral analysis | Spectral analysis of the RR interval is an indirect, noninvasive measurement tool of heart rate variability. High-frequency RR signal (greater than 0.15 Hz) is associated with increased parasympathetic tone, and low-frequency RR signal (0.04-0.15 Hz) is associated with increased sympathetic tone. | Day 8 | 
| High frequency in spectral analysis | Spectral analysis of the RR interval is an indirect, noninvasive measurement tool of heart rate variability. High-frequency RR signal (greater than 0.15 Hz) is associated with increased parasympathetic tone, and low-frequency RR signal (0.04-0.15 Hz) is associated with increased sympathetic tone. | Day 29 | 
| High frequency in spectral analysis | Spectral analysis of the RR interval is an indirect, noninvasive measurement tool of heart rate variability. High-frequency RR signal (greater than 0.15 Hz) is associated with increased parasympathetic tone, and low-frequency RR signal (0.04-0.15 Hz) is associated with increased sympathetic tone. | One time point between day 60 and day 90 | 
| Montgomery Asberg Depression Rating Scale (MADRS) | The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. A total superior to 20/60 is generally considered abnormal. A level of 30 points is considered a definition of severe depression. | Baseline (day 1) | 
| Montgomery Asberg Depression Rating Scale (MADRS) | The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. A total superior to 20/60 is generally considered abnormal. A level of 30 points is considered a definition of severe depression. | Day 8 | 
| Montgomery Asberg Depression Rating Scale (MADRS) | The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. A total superior to 20/60 is generally considered abnormal. A level of 30 points is considered a definition of severe depression. | Day 29 | 
| Montgomery Asberg Depression Rating Scale (MADRS) | The Montgomery-Åsberg Depression Rating Scale (MADRS) is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. A total superior to 20/60 is generally considered abnormal. A level of 30 points is considered a definition of severe depression. | One time point between day 60 and day 90 |