Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04532190 |
| Other study ID # |
REB20-1415 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 31, 2022 |
| Est. completion date |
December 31, 2025 |
Study information
| Verified date |
February 2022 |
| Source |
University of Calgary |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
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.
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those without (unpublished).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).
