Finding Alternatives to Standard Treatment for Attention-Deficit Hyperactivity Disorder (FAST-ADHD)

Attention-Deficit/Hyperactivity Disorder (ADHD) is characterized by poor attention, impulsivity, hyperactivity and emotional-motivational dysregulation. Here, we will test if repetitive transcranial magnetic stimulation (rTMS) can reduce the symptoms of ADHD.

Study Overview

• Status: Not yet recruiting
• Conditions: Attention-Deficit/Hyperactivity Disorder (ADHD)
• Intervention / Treatment: Device: rTMS

Detailed Description

1. Background & Rationale Attention-Deficit/Hyperactivity Disorder (ADHD) is characterized by poor attention, impulsivity, hyperactivity and emotional-motivational dysregulation. It has an estimated prevalence of 5% in children. Usually, ADHD in children is treated with stimulant medications, such as methylphenidate. However, these pharmacotherapy treatments have numerous unwanted side effects, including sleep disturbances, appetite changes, and emotional lability, and do not prove to be effective in every case.

   A promising and alternative option for reducing ADHD symptoms is non-invasive brain stimulation. Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive brain stimulation which involves the application of a magnetic field to the skull to change the behaviour and function of underlying brain areas. In turn, rTMS leads to positive long-term changes in neurochemical activity, and while studies are limited, some have shown that rTMS can reduce ADHD symptoms in adolescents with ADHD. In two separate neuroimaging studies, our team has shown that cortical thickness of the right superior frontal gyrus (r-SFG) is different in children with ADHD compared to those without (unpublished). Intriguingly, thinner r-SFG was associated with increased inattention and hyperactive behaviour, as measured by the Conners-3 Parent Rating Scale. Another recent study, in adults with ADHD, showed that high frequency rTMS to the right prefrontal cortex (which shares cortical space with the r-SFG) reduced ADHD symptoms. Moreover, studies have shown hypoactivity of the right superior frontal gyrus in individuals with ADHD. Therefore, in keeping with our findings, the primary aim of this study is to use rTMS to stimulate the r-SFG in children and adolescents with ADHD, hypothesizing that stimulating the r-SFG will lead to a reduction in ADHD symptoms. Parts of the superior frontal gyrus are anatomically and functionally connected to the cognitive control network. In line with this, cognitive control impairments are prevalent in individuals with ADHD. Participants will be randomly assigned to receive 4 weeks of active or sham (non-active) rTMS. Active and sham rTMS look and sound the same; the difference is that sham rTMS has no magnetic field emitted from the TMS coil, thereby acting as a placebo condition.

2. Research Question & Objectives Furthermore, this study will examine brain chemistry before and after rTMS treatment as we recently showed that children with ADHD have decreased concentrations of glutamate in their right prefrontal cortex compared to typically developing children. This previous study also showed that gamma-Aminobutyric acid (GABA) concentrations in the supplementary motor area (part of the superior frontal gyrus) were significantly higher in children with ADHD compared to typically developing controls. Thus, as the secondary aim, we will examine the impact of rTMS on the participant's neurobiology (i.e. brain chemistry (e.g. glutamate/GABA concentrations)). Finally, most studies only investigate the effects of treatment on ADHD symptom severity and do not look further at the effects on everyday functioning. The core symptoms of ADHD (hyperactivity and inattentiveness) are biologically and functionally intertwined with downstream effects on overall daily functioning including academic success and peer relationships. Therefore, the third exploratory aim of this study is to investigate the behavioural outcomes of rTMS on several aspects of cognitive functioning and academic performance, and quality of life of children with ADHD.
3. Methods Design: Sham-TMS controlled trial. (Sham rTMS vs Active rTMS) Primary Outcome: To examine the effect of active rTMS over the right superior frontal gyrus on ADHD symptoms, as measured by the Conners-3 Parent Rating Scale.

Secondary Outcomes: To examine the impact of rTMS treatment on the neurobiology (glutamate and GABA concentrations) of the right superior frontal gyrus.

Outline:

1. Baseline Assessment (MRI Scan, assessment scales, neuropsychological testing)
2. rTMS intervention: 5 x week for 4 weeks. Active repetitive TMS parameters will be intensity 120% resting motor threshold (RMT), 40 pulses over 4 seconds (frequency 10Hz), inter-trial interval of 26 seconds, 75 trains, 3000 pulses/session to the right superior frontal gyrus, duration of 37.5 minutes per session. For sham rTMS, set-up, duration, and sound (i.e. clicking sound) will be the same, but no magnetic field will be emitted from the rTMS coil.
3. Post-intervention Assessment (MRI Scan, assessment scales, neuropsychological testing).

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of ADHD
2. 8-16 years old
3. IQ greater than 80
4. English fluency (to enable consent/assent)
5. If on medication, must have been on the same type and dosage for at least 3 months.

Exclusion Criteria:

1. Diagnosis of mania, psychosis, or bipolar disorder
2. Impediments to TMS or MRI (i.e. metal implants in body)
3. Prior electroconvulsive therapy or vagus nerve stimulation
4. Prior diagnosis of post-concussive syndrome
5. Diagnosis of Autism Spectrum Disorder.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active rTMS; Active repetitive TMS parameters will be intensity 120% resting motor threshold (RMT), 40 pulses over 4 seconds (frequency 10Hz), inter-trial interval of 26 seconds, 75 trains, 3000 pulses/session to the right superior frontal gyrus, duration of 37.5 minutes per session.	Device: rTMS; Repetitive transcranial magnetic stimulation (rTMS)
Sham Comparator: Sham rTMS; For sham rTMS, set-up, duration, and sound (i.e. clicking sound) will be the same, but no magnetic field will be emitted from the rTMS coil.	Device: rTMS; Repetitive transcranial magnetic stimulation (rTMS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conners-3 Parent Rating Scale	Conners-3 Parent Rating Scale for ADHD Symptoms	Baseline to week 5 (a reduction is an improvement)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glutamate Concentration	Right superior frontal gyrus glutamate	Baseline to week 5 (an increase is an improvement)
GABA Concentration	Right superior frontal gyrus GABA	Baseline to week 5 (a decrease is an improvement)

Collaborators and Investigators

• Sponsor: University of Calgary

Study record dates

Study Major Dates

• Study Start (Anticipated): August 31, 2022
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: August 25, 2020
• First Posted (Actual): August 31, 2020

Study Record Updates

• Last Update Posted (Actual): February 8, 2022
• Last Update Submitted That Met QC Criteria: February 5, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Repetitive transcranial magnetic stimulation (rTMS); Attention-Deficit/Hyperactivity Disorder (ADHD
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Disease; Attention Deficit Disorder with Hyperactivity; Hyperkinesis
• Other Study ID Numbers: REB20-1415

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: If we do make individual participant data (IPD) available to other researchers it will be in keeping with local provincial laws on health information privacy. Data (if available) will be provided upon request.

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