Treatment of ADHD Using High and Low Frequency Paired Associative Deep Transcranial Magnetic Stimulation

NCT07105475 | Recruiting FDA Device

• 1 other identifier: 0152-23-SOR
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates the effects of high and low-frequency paired associative deep transcranial magnetic stimulation (dTMS) on adults with Attention Deficit Hyperactivity Disorder (ADHD). The study aims to explore whether targeting the prefrontal cortex with paired stimulation can improve symptoms of ADHD by balancing cortical arousal between the brain hemispheres. A total of 90 participants with ADHD will be recruited. Participants with ADHD will undergo three weeks of daily TMS treatment, while participants who receive a sham treatment will be included for baseline comparisons. The study will measure electrophysiological, cognitive, and clinical outcomes using a variety of assessments, including EEG, cognitive tests, and CAARS to evaluate the treatment's efficacy.

Conditions

Attention Deficit Hyperactivity Disorder; Neurodevelopmental Disorders; Prefrontal Cortex Dysregulation; Cortical Arousal Imbalance

Keywords

ADHD; Transcranial Magnetic Stimulation (TMS); Paired Associative Stimulation (PAS); Prefrontal Cortex; Hemispheric Asymmetry

Outcome Measures

Primary Outcomes (5)

• Change in ADHD Symptoms Assessed by the Conners' Adult ADHD Rating Scale (CAARS)

  This measure evaluates the change in ADHD symptom severity using the Conners' Adult ADHD Rating Scale (CAARS), a standardized and validated assessment tool. The CAARS provides subscale scores (e.g., Inattention, Hyperactivity-Impulsivity, ADHD Index) on a scale ranging from 0 to 100, with higher scores indicating greater symptom severity. Change will be assessed by comparing scores obtained at baseline (pre-treatment) and following the intervention (post-treatment), as well as at 1-month and 2-month follow-up visits.

  Pre-treatment (baseline) and post-treatment assessments at the end of the 3-week treatment phase, with follow-up assessments at 1 month and 2 months after treatment to evaluate sustained symptom improvement.

• Change in Cognitive Control Assessed by Stroop Task Performance

  This measure assesses changes in participants' cognitive control by comparing pre-treatment and post-treatment performance on the Stroop Task. Performance is evaluated based on reaction time (milliseconds) and accuracy (% correct responses) in congruent and incongruent trials. Lower reaction times and higher accuracy typically indicate better cognitive control, but outcome-neutral interpretation will be used to assess change.

  Pre-treatment (baseline) and post-treatment (immediately after the 3-week treatment phase). Additional assessments may be conducted during follow-up sessions at 1 month and 2 months after treatment.

• Change in Working Memory Assessed by N-back Task Performance

  This measure evaluates working memory by comparing participants' pre-treatment and post-treatment performance on the N-back task (2-back condition). Performance is quantified by reaction time (milliseconds) and accuracy (% correct target detections). Lower reaction times and higher accuracy reflect stronger working memory performance, but results will be analyzed in a directionally neutral manner.

  Pre-treatment (baseline) and post-treatment (immediately after the 3-week treatment phase). Additional assessments may be conducted during follow-up sessions at 1 month and 2 months after treatment.

• Change in EEG Power Spectral Density Across Frequency Bands

  This outcome assesses changes in EEG power spectral density (PSD) in the delta (0.5-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), and beta (13-30 Hz) frequency bands during resting-state EEG. PSD will be calculated using Fourier-based spectral analysis and reported in microvolts squared per hertz (µV²/Hz) at frontal and motor cortex sites.

  Baseline (pre/post Session 1), end of treatment (pre/post Session 15), and at 1-month and 2-month follow-ups. EEG is recorded during rest, cognitive tasks, TMS, TEP, and post-treatment rest at each time point.

• Change in Raw EEG Voltage

  This outcome measures the overall amplitude of raw EEG signals recorded at rest. Changes in baseline EEG voltage levels will be evaluated across treatment sessions and follow-ups to assess general cortical excitability. Unit of Measure: Microvolts (µV).

  Baseline (pre/post Session 1), end of treatment (pre/post Session 15), and at 1-month and 2-month follow-ups. EEG is recorded during rest, cognitive tasks, TMS, TEP, and post-treatment rest at each time point.

Secondary Outcomes (6)

• Long-Term Change in ADHD Symptoms Assessed at Follow-Up by Conners' Adult ADHD Rating Scale (CAARS)

  Assessed during follow-up sessions at 1 month and 2 months after the end of the 3-week treatment phase to evaluate the persistence of treatment effects.

• Long-Term Change in Cognitive Control Assessed at Follow-Up by Stroop Task Performance

  Assessed during follow-up sessions at 1 month and 2 months after the end of the 3-week treatment phase to evaluate the persistence of treatment effects.

• Long-Term Change in Working Memory Assessed at Follow-Up by N-back Task Performance

  Assessed during follow-up sessions at 1 month and 2 months after the end of the 3-week treatment phase to evaluate the persistence of treatment effects.

• Change in Amplitude of TMS-Evoked Potential (TEP) Components

  Baseline (pre/post Session 1), end of treatment (pre/post Session 15), and at 1-month and 2-month follow-ups. EEG is recorded during rest, cognitive tasks, TMS, TEP, and post-treatment rest at each time point.

• Change in Variance of TMS-Evoked Potentials (TEPs)

  Baseline (pre/post Session 1), end of treatment (pre/post Session 15), and at 1-month and 2-month follow-ups. EEG is recorded during rest, cognitive tasks, TMS, TEP, and post-treatment rest at each time point.

Other Outcomes (1)

• Incidence of Adverse Events Reported During and After TMS Treatment

  Monitored throughout the 3-week treatment, with documentation of any adverse effects during each treatment session. Follow-up assessments at 1 month and 2 months post-treatment will monitor for any delayed side effects or long-term tolerability issues.

Study Arms (3)

Low-Frequency Active PAS Treatment (ADHD Patients)

EXPERIMENTAL

Participants in this group will undergo three weeks of low-frequency paired associative stimulation (PAS) treatment. This involves the application of TMS at a low frequency to stimulate brain areas, specifically targeting the prefrontal cortex, to potentially improve symptoms of ADHD. The treatment will be administered five days a week for three weeks.

Device: Paired Associative Transcranial Magnetic Stimulation (TMS)

High-Frequency Active PAS Treatment (ADHD Patients)

EXPERIMENTAL

Participants in this group will receive three weeks of high-frequency PAS treatment. High-frequency TMS will be applied to stimulate brain areas, particularly the prefrontal cortex, to enhance cortical arousal and improve ADHD symptoms. This treatment will also be administered five days a week for three weeks.

Device: Paired Associative Transcranial Magnetic Stimulation (TMS)

Low-Frequency Sham PAS Treatment (ADHD Patients)

PLACEBO COMPARATOR

This group will undergo three weeks of sham PAS treatment, where the procedure mimics the active treatment but with the magnetic stimulation at a minimal power (20% of the subject's motor threshold). The goal is to serve as a placebo control to evaluate the effectiveness of the active treatments. This sham treatment will be administered five days a week for three weeks.

Device: Paired Associative Transcranial Magnetic Stimulation (TMS)

Interventions

Paired Associative Transcranial Magnetic Stimulation (TMS) DEVICE

Transcranial Magnetic Stimulation (TMS) is a non-invasive technique that uses magnetic fields to stimulate nerve cells in the brain. By placing a coil on the scalp, TMS generates magnetic pulses that induce electrical currents in specific brain regions. This can alter brain activity and potentially influence behavior and symptoms of various neurological and psychiatric conditions. PAS involves the use of transcranial magnetic stimulation (TMS) at a low and high frequency to stimulate the prefrontal cortex at different areas of the brain. The goal is to assess its effects on cortical arousal and ADHD symptoms. Participants will receive daily sessions of this stimulation for three weeks, with the stimulation designed to influence brain activity and potentially alleviate symptoms of ADHD.

Also known as: Low-Frequency Paired Associative Stimulation (PAS), High-Frequency Paired Associative Stimulation (PAS)

High-Frequency Active PAS Treatment (ADHD Patients); Low-Frequency Active PAS Treatment (ADHD Patients); Low-Frequency Sham PAS Treatment (ADHD Patients)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged 21-65.
• Aligned with the diagnosis of ADHD according to the criteria of the DSM-5.
• Participants taking medication for the treatment of attention deficit hyperactivity disorder will be asked, starting one week before the start of the treatment until the end, to take Ritalin IR 10mg (provided that the taking of the medication will be done at least 8 hours before the start of the treatment or at least one hour after it. This instruction is also valid for taking the medication on the days of the follow-up sessions (4 and 8 weeks from the end of the daily treatment phase). Ritalin is given as the only option because a drug with a short half-life is needed. The dose can be increased up to 20 mg per dose). The choice of this drug is to ensure that changes in brain function/activity are not the result of the Ritalin medication but of the research intervention.
• Give their written and oral consent to participate in the study.

You may not qualify if:

• Additional active psychiatric disorders in Axis I of the DSM-5.
• Antipsychotic treatment, antidepressants, or mood stabilizers.
• History of intolerance to TMS.
• Diagnosis of severe personality disorder according to the DSM-5.
• Current suicidal tendency.
• High and uncontrolled blood pressure.
• History of epilepsy, seizures or febrile seizures.
• History of epilepsy or seizures in first degree relatives.
• History of a head injury or major stroke that produced impairment.
• History of metal in the head (outside the oral cavity).
• History of surgery involving metal implants or a known history of metal particles in the eye, pacemakers, hearing aid implantation, use of neurostimulators, or any medical pump.
• History of drug or alcohol addiction.
• Inability to adequately communicate with the examiner.
• Participation in another medical study at the time of conducting the experiment or 3 months before it.
• Inability of the subject to sign a consent form.

Sponsors & Collaborators

• Ben-Gurion University of the Negev: lead
• Soroka University Medical Center: collaborator

Study Sites (1)

Ben Gurion University of the Negev

Beersheba, Israel

RECRUITING

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity; Neurodevelopmental Disorders

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Mental Disorders

Study Officials

• Abraham Zangen

  Ben-Gurion University of the Negev

  STUDY DIRECTOR

• Hadar Shalev

  Soroka University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abraham Zangen

CONTACT

+972 8-647-2646; azangen@bgu.ac.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 13, 2025
• First Posted: August 6, 2025
• Study Start: July 19, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: August 6, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)