Biological and Psychological Markers After Intervention in Adults With GAD

NCT07116980 | Completed

• 1 other identifier: 69019123.3.0000.5327
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial inestigates the effects of transcranial direct current stimulation (tDCS) on anxiety symptoms in adult women with clinically relevant anxiety levels. The intervention involves the application of low-intensity electrical current over the left dorsolateral prefrontal cortex (DLPFC) across twenty consecutive sessions. Participants are randomly assigned to either an active or sham stimulation group in a double-blind design. The study aims to evaluate changes in anxiety symptoms, emotional regulation, and physiological and molecular markers, including EEG activity, heart rate variability (HRV), and salivary levels of cortisol and interleukin-6 (IL-6) plasma. The findings are expected to support the development of complementary, low-cost, and non-pharmacological strategies for anxiety management.

Conditions

Anxiety

Keywords

anxiety; tDCS; IL-6; Cortisol; HRV; EEG

Outcome Measures

Primary Outcomes (1)

• Change in Generalized Anxiety Symptoms as Assessed by the GAD-7 Scale

  Change in anxiety symptoms will be assessed by the total change in the GAD-7 score, a 7-item self-administered scale that measures the severity of anxiety symptoms. Scores range from 0 to 21, with higher scores indicating greater anxiety severity.

  1 month

Secondary Outcomes (6)

• Change in the Anxiety Sensitivity Index-Revised (ASI-R) Total Score

  1 month

• Change in Pain Intensity as Measured by the Central Sensitization Inventory (CSI) score

  1 month

• Change in Subjective Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) score

  1 month

• Change in Absolute Alpha Band Power (8-12 Hz) at Electrode Site [F3/F4/C3/C4/P3/P4] as Assessed by Electroencephalogram (EEG).

  1 month

• Change in Heart Rate Variability (HRV) as Assessed by the Standard Deviation of NN Intervals (SDNN)

  1 month

Study Arms (2)

responds to the placebo effect Intervention: Transcranial Direct Current Stimulation - tDCS

PLACEBO COMPARATOR

Patients will receive tDCS stimulation treatment dorsolateral prefrontal cortex. According to the 10-20 EEG system, the anode will be placed on the left F3 and the cathode on the contralateral F4. Placebo stimulation uses a current of 2 milliamps for the first 30 seconds and again for the last 30 seconds. The tDCS application time will be 20 minutes Device: s-tDCS - Intervention: tDCS is a therapeutic method that modulates the membrane potential, where anodic stimuli induce cortical excitability and cathodic stimuli reduce it Device: a-tDCS \- Intervention: tDCS is a therapeutic method that modulates the membrane potential, where anodic stimuli induce cortical excitability and cathodic stimuli reduce it

Device: 'Transcranial Direct Current Stimulation - tDCS

No placebo effect responds Intervention: Transcranial Direct Current Stimulation - tDCS

ACTIVE COMPARATOR

Patients will receive tDCS stimulation treatment dorsolateral prefrontal cortex According to the 10-20 EEG system, the anode will be placed on the left F3 and the cathode on the contralateral F4. Active stimulation uses a current of 2 milliamps for 20 minutes. Device: s-tDCS - Intervention: tDCS is a therapeutic method that modulates the membrane potential, where anodic stimuli induce cortical excitability and cathodic stimuli reduce it Device: a-tDCS \- Intervention: tDCS is a therapeutic method that modulates the membrane potential, where anodic stimuli induce cortical excitability and cathodic stimuli reduce it

Device: 'Transcranial Direct Current Stimulation - tDCS

Interventions

'Transcranial Direct Current Stimulation - tDCS DEVICE

Participants will receive by trained personnel, transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (DLPFC). According to the international 10-20 EEG system, the anodal electrode will be placed over the left F3 position and the cathodal electrode over the right F4 position. Active stimulation will be delivered using a constant current of 2 milliamperes (mA) for 20 minutes per session. The intervention will consist of twelve consecutive daily sessions (Monday to Friday), totaling four week of treatment. A certified tDCS device will be used, programmed to deliver a ramp-up and ramp-down period of 30 seconds. In the sham condition, the same electrode montage will be used; however, the device will automatically ramp down the current after 30 seconds, mimicking the initial tingling sensation without producing lasting neuromodulatory effects. This sham protocol is commonly used to ensure participant blinding in tDCS studies.

No placebo effect responds Intervention: Transcranial Direct Current Stimulation - tDCS; responds to the placebo effect Intervention: Transcranial Direct Current Stimulation - tDCS

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adults under the age of 18;
• GAD-7 ≥ 10
• Possibility of being present on previously agreed days.

You may not qualify if:

• Being in psychopharmacological treatment for depression;
• HAM-D≥23 scale;
• have a self-reported severe disorder (psychosis, schizophrenia, substance abuse, major depression);
• having had seizures and epilepsy;
• having presented substance use disorder (except Tobacco) in the last 6 months or Suicidal Ideation in the last 6 months;
• being pregnant or breastfeeding;
• have suffered any type of brain injury or surgery, heart disease or cranial defect.

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator

Study Sites (1)

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Related Publications (6)

• Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, Mourdoukoutas AP, Kronberg G, Truong D, Boggio P, Brunoni AR, Charvet L, Fregni F, Fritsch B, Gillick B, Hamilton RH, Hampstead BM, Jankord R, Kirton A, Knotkova H, Liebetanz D, Liu A, Loo C, Nitsche MA, Reis J, Richardson JD, Rotenberg A, Turkeltaub PE, Woods AJ. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimul. 2016 Sep-Oct;9(5):641-661. doi: 10.1016/j.brs.2016.06.004. Epub 2016 Jun 15.

  PMID: 27372845 BACKGROUND

• Chalmers JA, Quintana DS, Abbott MJ, Kemp AH. Anxiety Disorders are Associated with Reduced Heart Rate Variability: A Meta-Analysis. Front Psychiatry. 2014 Jul 11;5:80. doi: 10.3389/fpsyt.2014.00080. eCollection 2014.

  PMID: 25071612 BACKGROUND

• Dedoncker J, Brunoni AR, Baeken C, Vanderhasselt MA. A Systematic Review and Meta-Analysis of the Effects of Transcranial Direct Current Stimulation (tDCS) Over the Dorsolateral Prefrontal Cortex in Healthy and Neuropsychiatric Samples: Influence of Stimulation Parameters. Brain Stimul. 2016 Jul-Aug;9(4):501-17. doi: 10.1016/j.brs.2016.04.006. Epub 2016 Apr 12.

  PMID: 27160468 BACKGROUND

• Palm U, Hasan A, Strube W, Padberg F. tDCS for the treatment of depression: a comprehensive review. Eur Arch Psychiatry Clin Neurosci. 2016 Dec;266(8):681-694. doi: 10.1007/s00406-016-0674-9. Epub 2016 Feb 3.

  PMID: 26842422 BACKGROUND

• Shiozawa P, Leiva AP, Castro CD, da Silva ME, Cordeiro Q, Fregni F, Brunoni AR. Transcranial direct current stimulation for generalized anxiety disorder: a case study. Biol Psychiatry. 2014 Jun 1;75(11):e17-8. doi: 10.1016/j.biopsych.2013.07.014. Epub 2013 Aug 16. No abstract available.

  PMID: 23958182 BACKGROUND

• Brunoni AR, Vanderhasselt MA. Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: a systematic review and meta-analysis. Brain Cogn. 2014 Apr;86:1-9. doi: 10.1016/j.bandc.2014.01.008. Epub 2014 Feb 8.

  PMID: 24514153 BACKGROUND

MeSH Terms

Conditions

Anxiety Disorders

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Wolnei Caumo, PhD

  Hospital de Clinicas de Porto Alegre

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The researcher will receive equipment already programmed by a research assistant, therefore, the researcher who will deliver the tDCS to perform the stimulation will not know the programmed stimulation. Patients will be instructed to discuss aspects of treatment with the respective investigator. Two independent assessors who will not participate in consultations where guidance on the use of tDCS will be provided will be trained to assess follow-up outcomes. Patients will not know the type of intervention received, as the sham condition produces a stimulus, but without the expected effects. Blinding will be evaluated at the end of treatment using a standardized instrument.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, randomized, parallel-group, simulation-controlled clinical trial

Study Record Dates

• First Submitted: June 18, 2025
• First Posted: August 12, 2025
• Study Start: June 21, 2023
• Primary Completion: January 30, 2024
• Study Completion: June 25, 2024
• Last Updated: August 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)