tDCS and Psychotherapy for the Treatment of Anxiety Disorders (tDCSplusUP)

The Efficacy of Transcranial Direct Current Stimulation Combined With the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: a Double Blind, Sham Controlled, Randomized Factorial Designed Study for Anxiety Disorders

The main goal of the study is to test the efficacy of tDCS in combination with the Unified Protocol for transdiagnostic treatment of emotional disorders, to reduce anxiety symptoms in a mixed anxiety disorders sample, as assessed by the Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959).

Study Overview

• Status: Not yet recruiting
• Conditions: Anxiety Disorders
• Intervention / Treatment: Device: active tDCS; Behavioral: CBT-UP; Device: sham tDCS; Behavioral: Psychoeducation

Detailed Description

Participants will be randomly allocated to one of four parallel experimental arms, within a 2X2 factorial design in which two interventions (tDCS and CBT-UP) will be delivered, and assessed according to two levels (e.g., intervention vs. no intervention).

Each study participant will assigned to one factor level. Four intervention groups are defined

1. active tDCS + CBT-UP
2. sham tDCS + CBT-UP
3. active tDCS + Psychoeducation
4. sham tDCS + Psychoeducation

The four arms allow to experimentally control the two active therapeutic interventions: active tDCS and CBT-UP. Sham tDCS is the control for active tDCS and psychoeducation is the control condition for CBT-UP.

The intervention will last for 15 weeks, and all groups will comply with the same intervention structure according to the examination plan established in the protocol:

• week 1-2: 1 CBT-UP session/week
• week 3-4: 5 tDCS sessions and 1 CBT-UP session/week
• week 5-8: 2 tDCS sessions and 1 CBT-UP session/week
• week 9-14: 1 tDCS session and 1 CBT-UP session/week
• week 15: 1 CBT-UP session

The treatment will consist of 26 transcranial direct current stimulation sessions, each lasting 20 minutes, with a current intensity of 2 mA, the cathode placed over the right dorsolateral prefrontal cortex and the anode placed over the left deltoid muscle. tDCS will be combined with cognitive-behavioral therapy, in particular following the unified protocol for transdiagnostic treatment of emotional disorders (Barlow et al. 2018).

Safety:

No serious adverse effects are expected with conventional tDCS protocols in humans (≤40 min, ≤4 mA; conclusions from a meta-analysis observing >33200 sessions, >1000 subjects with repeated sessions; Bikson et al., 2016).

Plans for treatment or care after the subject has ended his/her participation in the trial:

Patients will be recommended and offered the best treatment as evidenced by the trial results. For patients that already completed that intervention further standard psychological/psychiatric treatment will be recommended according to patients' status.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of generalized anxiety disorder, specific phobia, panic disorder, agoraphobia, or social anxiety disorder.
• Willing to participate and to give written informed consent

Exclusion Criteria:

1. Contra-indications to tDCS use:

   • Presence of a cardiac or neurological condition
   • Metallic implants
   • If contact with scalp is not possible
   • Have had a head injury resulting in a loss of consciousness that has required further investigation
   • History of seizures
   • Epilepsy or a history of epilepsy
   • Past adverse effects with non-invasive stimulation treatments
2. Current diagnosis of another psychiatric disorder (except for depression, as long as secondary diagnosis), psychoactive medication or psychological treatment
3. Left-handedness
4. Pregnancy
5. Skin condition on the stimulation target area
6. Recreational drug use

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: active tDCS + CBT-UP; Active tDCS combined with the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders.	Device: active tDCS; 26 transcranial direct current stimulation sessions, each lasting 20 minutes, with a current intensity of 2 mA, the cathode placed over the right dorsolateral prefrontal cortex and the anode placed over the left deltoid muscle.; Other Names: Transcranial Direct Current Stimulation; Behavioral: CBT-UP; 15 psychotherapy sessions (1/week) following the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders developed by Barlow et al. 2018.
Active Comparator: sham tDCS + CBT-UP; Sham tDCS (control for active tDCS) combined with the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders.	Behavioral: CBT-UP; 15 psychotherapy sessions (1/week) following the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders developed by Barlow et al. 2018.; Device: sham tDCS; tDCS is controlled in this intervention: sham mode.
Active Comparator: active tDCS + Psychoeducation; Active tDCS combined with psychoeducation (control condition for CBT-UP).	Device: active tDCS; 26 transcranial direct current stimulation sessions, each lasting 20 minutes, with a current intensity of 2 mA, the cathode placed over the right dorsolateral prefrontal cortex and the anode placed over the left deltoid muscle.; Other Names: Transcranial Direct Current Stimulation; Behavioral: Psychoeducation; To control for the cognitive-behavioral intervention we will use psychoeducation materials.
Placebo Comparator: sham tDCS + Psychoeducation; Sham tDCS combined with psychoeducation (control conditions for active tDCS and CBT-UP).	Device: sham tDCS; tDCS is controlled in this intervention: sham mode.; Behavioral: Psychoeducation; To control for the cognitive-behavioral intervention we will use psychoeducation materials.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959)	The mean change in the Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) score, from baseline. HARS total score ranges from 0 to 56, where higher values indicate higher anxiety symptom's severity.	At week 8th, 15th (middle and end of treatment) and 6 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to treatment	Defined as reduction of total Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) score by ≥ 50%.	At week 8th, 15th (middle and end of treatment) and 6 months follow-up.
Remission to treatment	Defined as reduction of total Hamilton Anxiety Rating Scale (HARS; Hamilton, 1959) to scores lower than 18 (indicating mild anxiety severity).	At week 8th, 15th (middle and end of treatment) and 6 months follow-up.
Hamilton Depression Rating Scale (HRSD; Hamilton, 1960)	The mean change in the Hamilton Depression Rating Scale (HRSD; Hamilton, 1960) score, from baseline. HDRS total score ranges from 0 to 75, where higher values indicate higher depressive symptoms' severity.	At week 8th, 15th (middle and end of treatment) and 6 months follow-up.

Collaborators and Investigators

• Sponsor: University of Coimbra

Publications and helpful links

General Publications

• HAMILTON M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960 Feb;23(1):56-62. doi: 10.1136/jnnp.23.1.56. No abstract available.
• HAMILTON M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50-5. doi: 10.1111/j.2044-8341.1959.tb00467.x. No abstract available.
• 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.
• Barlow DH, Farchione TJ, Bullis JR, Gallagher MW, Murray-Latin H, Sauer-Zavala S, Bentley KH, Thompson-Hollands J, Conklin LR, Boswell JF, Ametaj A, Carl JR, Boettcher HT, Cassiello-Robbins C. The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders Compared With Diagnosis-Specific Protocols for Anxiety Disorders: A Randomized Clinical Trial. JAMA Psychiatry. 2017 Sep 1;74(9):875-884. doi: 10.1001/jamapsychiatry.2017.2164.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 3, 2023
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: June 26, 2020
• First Submitted That Met QC Criteria: June 26, 2020
• First Posted (Actual): July 1, 2020

Study Record Updates

• Last Update Posted (Actual): May 20, 2022
• Last Update Submitted That Met QC Criteria: May 19, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: tDCS; RCT; Unified Protocol; anxiety disorders
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Disease; Anxiety Disorders
• Other Study ID Numbers: tDCS-UP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

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