Large-scale Brain Organization During Cognitive Control in ADHD

University of North Carolina (UNC)

Status and phase: Completed; Phase 4

Conditions: Attention Deficit Hyperactivity Disorder

Treatments: Drug: Methylphenidate; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04349917

R00MH102349 (U.S. NIH Grant/Contract)

16-0112

Details and patient eligibility

About

The purpose of this study is to test whether children with attention-deficit/hyperactivity disorder (ADHD) are impaired in the ability to flexibly adapt brain network organization in response to shifting cognitive demands during the exertion of cognitive control, by assessing changes in network dynamics resulting from stimulant administration in children with ADHD, and how those changes relate to behavioral and symptom improvements. Subjects will be children with ADHD aged 8-12. Subjects will participate in multiple testing sessions that include: diagnosis and eligibility screening, neuropsychological and behavioral testing, and, if eligible, MRI scans and a medication challenge. Children with ADHD who are enrolled in the medication challenge will undergo one MRI scan on placebo and one MRI scan on stimulant medication, counterbalanced and double-blind. Functional connectivity will be measured using functional MRI and innovative graph theoretical analytic tools will be implemented. Network metrics will be related to symptomatology and behavioral testing measures. It is hypothesized that stimulant administration in children with ADHD will increase flexibility in network reconfiguration in response to changing cognitive control demands as compared to when they are on placebo. It is further hypothesized that the degree to which brain network organization is changed will be related to the degree of improvement in cognitive control performance.

Enrollment: 37 patients

Sex: All

Ages: 8 to 12 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Between 8-12 years old
• Diagnosis of ADHD (for ADHD group); ADHD group only can have comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnoses of oppositional defiant disorder, conduct disorder, depressive disorders, or anxiety disorders
• ADHD subjects must never have been treated with medication for their ADHD

Exclusion criteria

• Wechsler Intelligence Scale for Children-Fifth Edition Full-Scale Intelligence Quotient (IQ) < 80
• Wechsler Individual Achievement Test-Third Edition Word Reading < 85
• Any neurologic or developmental disabilities
• Any reading or learning disabilities
• Visual impairment that cannot be corrected-to-normal
• Color blindness
• Documented hearing impairment greater than 25 decibels (dB) loss in either year
• Have already gone through puberty (Tanner Stage II or higher)
• Medical contraindication to MRI
• Any psychoactive medication

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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37 participants in 2 patient groups, including a placebo group

Placebo, then Methylphenidate

Placebo Comparator group

Description:

All children with ADHD in this study will receive one dose of methylphenidate and one dose of placebo over the course of two sessions approximately one week apart (order randomized and double-blind).

Treatment:

Other: Placebo

Drug: Methylphenidate

Methylphenidate, then Placebo

Experimental group

Description:

All children with ADHD in this study will receive one dose of methylphenidate and one dose of placebo over the course of two sessions approximately one week apart (order randomized and double-blind).

Treatment:

Other: Placebo

Drug: Methylphenidate