ADHD
Conditions
Brief summary
The objective of this clinical trial is to examine whether non-invasive brain stimulation can modulate dysfunctional brain dynamics underlying adolescent ADHD to subsequently improve clinical symptoms.
Detailed description
Working memory (WM) is the foundational cognitive control process of holding information 'in mind' to execute goal-directed behaviors. WM deficits are an established component of all primary childhood psychiatric disorders, most notably ADHD. Despite being one of the strongest predictors of poor clinical and functional outcomes in pediatric mental health, there remains a dearth of available treatments for WM deficits. Non-invasive brain stimulation holds tremendous promise in transforming psychiatry, as it takes a brain-first approach to treatment. The dorsolateral prefrontal cortex (DLPFC) is the known structural foundation of WM, and the interaction between slow and fast brain waves (i.e., theta-gamma coupling \[TGC\]) is a neural, functional foundation of WM. Thus, the DLPFC and TGC are potential brain-based targets for the modulation of WM with brain stimulation. Intermittent theta burst stimulation (iTBS) is a novel paradigm that applies a three-minute dose of stimulation to the DLPFC at an intensity that directly mimics TGC dynamics. The objective of this study is to utilize the experimental therapeutics approach to investigate whether iTBS can lead to a lasting modulation of WM-related neural oscillations. In a crossover, double-blind design, a sample of adolescents (12-18 years old) with ADHD and WM deficits will complete a two-week course of active iTBS and a two-week course of sham iTBS to their left DLPFC. The central hypothesis is that iTBS at the left DLPFC will modulate TGC and subsequently improve attentional/WM abilities in adolescent WM deficits. Aim 1 will examine the effect of iTBS on TGC and attention/WM (i.e., target engagement). Aim 2 will examine the relationship between change in TGC and attention/WM performance and symptoms (i.e., target validation). The exploratory aim will identify the neocortical circuitry underlying oscillatory modulation. A secondary and clinical objective is to examine the safety/tolerability and preliminary efficacy of iTBS on ADHD-related symptoms. Participants that complete the primary study procedures will be offered the opportunity to receive more iTBS sessions via participation in an optional open label arm. Participants will have the option of selecting an accelerated iTBS approach or the traditional, daily iTBS approach. Both approaches will administer 1800 pulses of iTBS to the left DLPFC per session. The accelerated protocol will administer iTBS twice per day for 10 days and the traditional protocol will administer iTBS once per day for 20 days.
Interventions
DEVICEIntermittent Theta Burst Stimulation to the Left Dorsolateral Prefrontal Cortex
iTBS will be administered to the left DLPFC for 10 consecutive days
Sponsors
Bradley Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Ability to provide assent and have parent provide parental permission 2. English fluency of the participant and the legal guardian/parent 3. 12-18 years 4. Parent rating on BRIEF-2 Working Memory: Greater than 1.0 SD above normative mean. 5. IQ \> 80 6. Clinical diagnosis of attention deficit hyperactivity disorder (ADHD): predominantly inattentive type, predominantly hyperactive/impulsive type, combined type, or unspecified type. Diagnostic criteria will be confirmed with NICHQ Vanderbilt Assessment Scales-Parent. 7. Participants are allowed to continue clinical ADHD treatments. However, changes to ADHD treatments cannot be made during the entirety of study participation. Confirming a plan of treatment stability will occur as part of initial inclusion criteria. We will check on treatment stability at the start of each two-week phase with the participant and parent, and document accordingly. Changes to treatment will be reviewed by a physician and may result in study termination.
Exclusion criteria
Participants will be screened to exclude individuals with neurological or medical conditions that might confound the results, as well as to exclude participants in whom MRI or TMS might result in increased risk of side effects or complications. Common contraindications include metallic hardware in the body, cardiac pacemaker, patients with an implanted medication pumps or an intracardiac line, or prescription of medications known to lower seizure threshold. These account for the majority of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Theta-Gamma Coupling | Theta-gamma coupling will be obtained before the 1st session, and 24 hours after the 1st, 5th, and 10th sessions. Statistical modeling will examine the CHANGE across these four time points. This change is considered a single primary outcome variable. | EEG recording will be obtained while the participant completes the Sternberg Spatial Working Memory Test (SWMT). The coupling between theta phase and gamma amplitude will be extracted from the EEG during encoding and maintaining demands. |
| Change in Parent-Reported ADHD, Working Memory, and Affective-Related Symptoms | ADHD/WM/affective symptoms will be obtained before the 1st session, and 24 hours after the 5th, and 10th sessions. Statistical modeling will examine the CHANGE across these time points. This change is considered a single primary outcome variable. | Parents complete the BRIEF-2/Vanderbilt/PROMIS forms |
| Change in Working Memory Test Performance | SSWMT performance will be obtained before the 1st session, and 24 hours after the 1st, 5th, and 10th sessions. Statistical modeling will examine the CHANGE across these four time points. This change is considered a single primary outcome variable. | Participants complete the Sternberg Spatial Working Memory Test |
Countries
United States
Outcome results
None listed