TDCS for the Treatment of Inattention Symptoms in Adult ADHD Patients (TUNED)

Transcranial Direct Current Stimulation for the Treatment of Inattention Symptoms in Attention-deficit/Hyperactivity Disorder: a Randomized, Double-blind, Parallel, Controlled Clinical Trial (TUNED Trial)

This study aims at evaluating the efficacy and safety of a home-based tDCS device when compared to a sham stimulation for improving attention in adult ADHD patients.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Device: Home-based transcranial direct current stimulation

Detailed Description

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by age inappropriate symptoms of inattention, hyperactivity-impulsivity, or both. The diagnosis of ADHD correlates with several negative outcomes during childhood, adolescence and adulthood, creating huge direct and indirect costs for the health system. The treatment of ADHD involves the use of pharmacologic and non-pharmacologic approaches, and stimulant medications are the most commonly used. Although effective, stimulant medication presents several limitations, reducing long-term adherence. Transcranial direct current stimulation (tDCS) is a neuromodulatory tool that has been shown to be effective for the treatment of various neuropsychiatric disorders. Previous pilot studies applying tDCS in ADHD patients showed conflicting results, and were characterized by heterogeneous methodologies. This study aims at evaluating the effectiveness and safety of tDCS for improving attention in adult ADHD patients by using a more strict methodology, based on a pilot study from our group that showed promising results. Besides that, we aim at exploring the mechanisms of action involved in the effect by using genomic and neuroimaging approaches. By using a computational model, we will also measure the association between clinical response and electric field density propagated with the use of tDCS in brain regions involved in attentional tasks. This will be a phase II-III, parallel, with two intervention groups, randomized, placebo-controlled and double blind study. Only patients without current pharmacological treatment for ADHD will be included in order to evaluate the effectiveness of tDCS as an alternative treatment for the disorder. Patients will be randomized to receive tDCS stimulation with either active or sham home-based devices. The stimulation protocol will include one daily stimulation during the first 4 weeks, 2 weekly stimulations for the next 4 weeks, and one weekly stimulation over the last 4 weeks. After the end of the 12 weeks of stimulation, patients will be followed-up during 6 months in order to observe for how long the effects last. The primary outcome will be obtained after the first 4 weeks of stimulation, with the use of a scale that evaluates inattention symptoms. We hypothesize that the active tDCS will reduce inattention symptoms when compared to sham stimulation, and will result in an increased activation of brain regions related to attention performance. In exploratory analyses, by using genomic approaches, we will observe possible associations between treatment response and specific genes, gene pools and polygenic risk scores. In addition, a functional magnetic resonance imaging test will be performed at rest and during both a sustained attention task (Sustained Attention Test), and a working memory task (N-back Test). This will be performed in order to measure the effects of treatment in the activation of brain regions related to attention performance before and after the first 4 weeks of stimulation.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-007
      • Hospital de Clínicas de Porto Alegre

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:

• Subject is willing and able to comply with all requirements of the study;
• Subject is able to provide written consent;
• Subject with an estimated Intelligent Quotient (IQ) score of 80 or above on the Wechsler Adult Intelligence Scale, Third Edition (WAIS-III);
• Subject has a diagnosis of ADHD (combined or inattentive subtypes) according to DSM-V;
• Subject scores 21 points or more in the Clinician Administered ADHD self-report scale - part A (inattention symptoms);
• Subject has not received pharmacological treatment for ADHD during the last month;
• If the subject receives pharmacological treatment for other medical conditions, he/she agrees to maintain the same dosage during the study time;
• Subject is classified as European descendent according to morphologic characteristics, color and ancestry.

Exclusion Criteria:

• Subject has a previous history of neurosurgery;
• Subject has any ferromagnetic metal in the head;
• Subject has implanted medical devices in the head or neck region;
• Subject has a history of non-controlled epilepsy with seizures in the last year;
• Subject has a current depressive episode with a Beck Depression Inventory > 21 points;
• Subject has a current anxiety episode with a Beck Anxiety Inventory > 21 points;
• Subject has a diagnosis of bipolar disorder with maniac or depressive episodes in the last year;
• Subject has a diagnosis of schizophrenia or another psychosis;
• Subject has a diagnosis of autism;
• Subject screened positive for substance use disorder according to The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST);
• Subject has an unstable medical condition with reduction of functional capacity in the next 6 months, like cancer, terminal cardiac disease or terminal pulmonary disease;
• Subject is pregnant or willing to become pregnant in the next 3 months;
• Subject is not able to use a home-based device.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Active tDCS; The anode will be placed over the right dorsolateral prefrontal cortex (DLPFC) and the cathode over the left DLPFC. Stimulation will be performed for 30 minutes with a current intensity of 2 mA. A ramp-up time of 20 s for the current to go from zero to 2 mA and a ramp-down time that also takes 20 s for the current to go from 2 mA to zero will be used.	Device: Home-based transcranial direct current stimulation; The stimulation protocol will include one daily stimulation during the first 4 weeks, 2 weekly stimulations for the next 4 weeks, and one weekly stimulation over the last 4 weeks.; Other Names: Home-based tDCS
SHAM_COMPARATOR: Sham tDCS; The same montage will be used. Sham stimulation will have the same ramp-up and ramp-down time in three different moments (beginning, middle and at the end of the session).	Device: Home-based transcranial direct current stimulation; The stimulation protocol will include one daily stimulation during the first 4 weeks, 2 weekly stimulations for the next 4 weeks, and one weekly stimulation over the last 4 weeks.; Other Names: Home-based tDCS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician Administered ADHD Self-Report Scale - part A (inattention) at Visit 4 (week 4)	The ADHD Self-Report Scale part A consists of 9 items designed to rate ADHD inattention symptoms. Each item is score from 0 to 4, with a total score ranging from 0 to 36 and higher scores indicating greater symptom severity. The scale will be administered by a clinician with the use of adult prompts.	Baseline, Visit 4 (week 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinician Administered ADHD Self-Report Scale - total score	The ADHD Self-Report Scale consists of 18 items designed to rate ADHD inattention and hyperactivity/impulsivity symptoms. Each item is score from 0 to 4, with a total score ranging from 0 to 72 and higher scores indicating greater symptom severity. The scale will be administered by a clinician with the use of adult prompts.	Baseline, Visit 4 (week 4), Visit 5 (week 8), Visit 6 (week 9), Visit 7 (week 10), Visit 8 (week 11), Visit 9 (week 12)
Behavior Rating Inventory of Executive Functioning - Adult Version (BRIEF-A)	This is a 75 item self-assessment questionnaire measuring distinct aspects of executive function.	Baseline, Visit 4 (week 4), Visit 5 (week 8), Visit 6 (week 9), Visit 7 (week 10), Visit 8 (week 11), Visit 9 (week 12)
Goal Achievement Scale	This is a questionnaire created in order to identify specific goals that patients would like to achieve with the proposed intervention, and how much they have achieved from each goal.	Baseline, Visit 4 (week 4), Visit 5 (week 8), Visit 6 (week 9), Visit 7 (week 10), Visit 8 (week 11), Visit 9 (week 12)
N-Back Test	In the N-Back Test subjects are going to be present to a series of letters and required to respond whenever the letter presented is the same as one, two or three before it.	Baseline, Visit 4 (week 4)
Sustained Attention Test	In the Sustained Attention Tests subjects are required to respond as quickly as possible to a visual stimulus.	Baseline, Visit 4 (week 4)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Depression Inventory	This is a 21 item rating scale for depression symptoms.	Baseline, Visit 4 (week 4), Visit 5 (week 8), Visit 6 (week 9), Visit 7 (week 10), Visit 8 (week 11), Visit 9 (week 12)
Beck Anxiety Inventory	This is a 21 item rating scale for anxiety symptoms.	Baseline, Visit 4 (week 4), Visit 5 (week 8), Visit 6 (week 9), Visit 7 (week 10), Visit 8 (week 11), Visit 9 (week 12)

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Luis Augusto Rohde, MD-PhD, Hospital de Clínicas de Porto Alegre

Publications and helpful links

General Publications

• Leffa DT, Grevet EH, Bau CHD, Schneider M, Ferrazza CP, da Silva RF, Miranda MS, Picon F, Teche SP, Sanches P, Pereira D, Rubia K, Brunoni AR, Camprodon JA, Caumo W, Rohde LA. Transcranial Direct Current Stimulation vs Sham for the Treatment of Inattention in Adults With Attention-Deficit/Hyperactivity Disorder: The TUNED Randomized Clinical Trial. JAMA Psychiatry. 2022 Sep 1;79(9):847-856. doi: 10.1001/jamapsychiatry.2022.2055.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2019
• Primary Completion (ACTUAL): July 21, 2021
• Study Completion (ACTUAL): February 18, 2022

Study Registration Dates

• First Submitted: June 28, 2019
• First Submitted That Met QC Criteria: June 28, 2019
• First Posted (ACTUAL): July 1, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 21, 2022
• Last Update Submitted That Met QC Criteria: February 18, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis
• Other Study ID Numbers: 2018-0658

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
• product manufactured in and exported from the U.S.: No