Randomized, Sham Controlled Study for the Treatment of ADHD Using High and Low Frequency Paired Associative Deep Transcranial Magnetic Stimulation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Change in ADHD Symptoms Assessed by the Conners' Adult ADHD Rating Scale (CAARS)
研究概览
简要总结
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.
详细描述
Introduction Transcranial Magnetic Stimulation (TMS) is a non-invasive technique that uses magnetic fields to stimulate nerve cells in the brain, potentially altering brain activities and influencing behavior. It has been applied in both healthy individuals and patients to study brain activity, behavior, and therapeutic effects. TMS can be administered as single pulses or repetitive stimuli, with the latter showing lasting effects beyond the treatment session. High-frequency TMS is FDA-approved for treating major depressive disorder, obsessive-compulsive disorder, and smoking cessation.
ADHD is a neurodevelopmental disorder characterized by inattention, impulsivity, and hyperactivity. Neuroimaging studies have identified deficits in brain regions such as the prefrontal cortex, basal ganglia, and cerebellum in ADHD patients. Enhancing activity in these areas, particularly the prefrontal cortex, through high-frequency TMS has shown promise in reducing ADHD symptoms.
Research Question and Hypothesis The study aims to assess the effectiveness of paired associative stimulation (PAS) in treating ADHD. It hypothesizes that right-to-left prefrontal paired stimulation can enhance cortical arousal and provide symptom relief. The study includes two active treatment groups (high and low-frequency PAS) and a sham treatment group, with secondary goals to quantify short- and long-term changes in behavior, brain function, and structure.
Methods
Participants Total: 90 ADHD patients ADHD patients: Pre-screened by a psychiatrist; will undergo three weeks of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women aged 21-
- •Aligned with the diagnosis of ADHD according to the criteria of the DSM-
- •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.
排除标准
- •Additional active psychiatric disorders in Axis I of the DSM-
- •Antipsychotic treatment, antidepressants, or mood stabilizers.
- •History of intolerance to TMS.
- •Diagnosis of severe personality disorder according to the DSM-
- •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.
- •Pregnancy or not giving a commitment not to get pregnant during the study period or having sex without using contraceptives.
结局指标
主要结局
Change in ADHD Symptoms Assessed by the Conners' Adult ADHD Rating Scale (CAARS)
时间窗: 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.
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.
Change in Cognitive Control Assessed by Stroop Task Performance
时间窗: 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.
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.
Change in Working Memory Assessed by N-back Task Performance
时间窗: 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.
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.
Change in EEG Power Spectral Density Across Frequency Bands
时间窗: 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.
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.
Change in Raw EEG Voltage
时间窗: 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.
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).
次要结局
- 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.)
- Change in EEG Frequency Characteristics(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.)
研究者
Zachary Katz
Principal Investigator
Ben-Gurion University of the Negev