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

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.

Study Overview

• Status: Completed
• Conditions: Anxiety Depression
• Intervention / Treatment: Device: Transcranial direct current stimulation (t-DCS) device

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1020
    • CHU Brugmann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active t-DCS; 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; 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.
Sham Comparator: Sham t-DCS; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tatiana Besse-Hammer
• Investigators: Principal Investigator: Pierre Cole, CHU Brugmann

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Actual): June 23, 2021
• Study Completion (Actual): June 23, 2021

Study Registration Dates

• First Submitted: December 3, 2019
• First Submitted That Met QC Criteria: December 5, 2019
• First Posted (Actual): December 6, 2019

Study Record Updates

• Last Update Posted (Actual): July 19, 2022
• Last Update Submitted That Met QC Criteria: July 18, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder
• Other Study ID Numbers: CHUB-PSY-COMBINTES 1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No