Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach

NCT01678209 | Completed Phase 4 Results DMC

• 2 other identifiers: GCO 11-01615R01MH095766-02
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

Brief Summary

The growing number of medications used to treat attention-deficit/hyperactivity disorder (ADHD) raises important questions about whether different medications have similar or different therapeutic mechanisms of action. We have recently shown that the stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) produce clinical improvement via a common mechanism in motor cortex, and distinct actions in frontostriatal and midline cingulate-precuneus regions. These exciting findings offer a window into the common and unique neurophysiological mechanisms of response to stimulant and non-stimulant treatments. However, the interpretation and clinical utility of these results would be greatly enhanced by in-depth investigation of the impact of the two treatments on relevant neural networks, and analyses which evaluate whether improvement is achieved via normalization or other adaptive changes in brain function.

Conditions

Attention Deficit Hyperactivity Disorder; ADHD

Keywords

Attention Deficit Hyperactivity Disorder; Stimulant; Non-stimulant; Drug; Methylphenidate; Atomoxetine; Strattera; Concerta; MACRO; Medication; Treatment; Youth; Adolescent; Functional Magnetic Resonance Imaging; Brain scan; Imaging; Response inhibition; Inattentive; Hyperactive; Combined; Medication Treatment; Brain Imaging

Outcome Measures

Primary Outcomes (1)

• Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task

  Comparison of Go-Nogo at 6 weeks from baseline. Performance on a go-nogo task inside the scanner (fMRI). In the go/no-go task, participants respond to certain stimuli ("go" stimuli) and make no response for others ("no-go" stimuli).

  Baseline and at 6 weeks

Secondary Outcomes (6)

• Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale (ADHD-RS)

  8 weeks

• Clinical Global Impressions-Severity (CGI-S)

  up to 6 weeks

• Response Time in Attention Networks Test (ANT)

  baseline and at 6 weeks

• Continuous Performance Test (CPT)

  baseline and at 6 weeks

• Digit Span

  baseline and at 6 weeks

Study Arms (3)

fMRI scans

ACTIVE COMPARATOR

Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart

Other: fMRI scans

Atomoxetine arm

EXPERIMENTAL

These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.

Other: fMRI scans; Drug: Atomoxetine arm

Methylphenidate arm

EXPERIMENTAL

Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.

Other: fMRI scans; Drug: Methylphenidate arm

Interventions

fMRI scans OTHER

2 fMRI scans 6-8 weeks apart

Atomoxetine arm; Methylphenidate arm; fMRI scans

Atomoxetine arm DRUG

Flexible dose titration with atomoxetine prescribed at weekly visits for 6-8 weeks

Also known as: Strattera, ATX

Atomoxetine arm

Methylphenidate arm DRUG

Flexible dose titration with methylphenidate for 6-8 weeks, with optional post study stabilization visits.

Also known as: Concerta, MPH

Methylphenidate arm

Eligibility Criteria

• Age: 7 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• aged 7-17 years;
• Wechsler Intelligence Scale for Children (WISC) scores ≥ 75;
• informed consent and assent to study participation.
• diagnosis of ADHD, any subtype, determined by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Versions (K-SADS-PL);
• ADHD Rating Scale-IV-Parent Version: Investigator Administered (ADHD-RSIV) total score ≥ 1.5 SD above age and gender means for subtype
• Clinical Global Impressions-ADHD-Severity (CGI-S) score \> 4;
• ADHD must be the primary diagnosis and focus of treatment, and the treatments offered in the study must not be contraindicated for the comorbid disorder.

You may not qualify if:

• history of head injury with loss of consciousness or any CNS disease that is likely to affect brain function;
• diagnosis of autism or pervasive developmental, psychotic, major mood, and Tourette's disorder;
• alcohol or drug abuse in the past 3 months or a positive urinary toxic screen on initial evaluation;
• use of psychotropic medication within 2 weeks of the study (8 weeks for fluoxetine);
• pre-existing medical or psychological condition which precludes being in the scanner (e.g., claustrophobia, morbid obesity);
• metal in the body that precludes scanning (e.g., braces, metal plate);
• positive urine pregnancy test.
• previous unsuccessful trial of MPH or ATX that was adequately dosed (≥ 1 mg/kg for MPH or 1.0 mg/kg for ATX) and of adequate duration (≥ 4 weeks);
• abnormal findings on physical exam, or vital signs
• pulse and blood pressure \> 95% of age and gender mean;
• inability to swallow capsules;
• weight is \< 20 kg or \> 85 kg.
• no past history or current diagnosis of any psychiatric disorder, determined by the K-SADS-PL interview;
• ADHD-RS-IV and CBCL scores for each symptom domain ≤ 1 SD of age and gender means.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity; Spasm

Interventions

Atomoxetine Hydrochloride; Methylphenidate; 5,10-dihydro-5-methylphenazine

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Beth Krone, PhD
• Organization: Icahn School of Medicine at Mount Sinai

beth.krone@mssm.edu

212-241-8014

Study Officials

• Jeffrey Newcorn, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Kurt Schulz, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Division of Child and Adolescent Psychiatry, Associate Professor Psychiatry and Pediatrics, Medical Director Center for Excellence for ADHD and Related Disorders

Study Record Dates

• First Submitted: August 30, 2012
• First Posted: September 3, 2012
• Study Start: October 1, 2012
• Primary Completion: April 30, 2018
• Study Completion: April 30, 2018
• Last Updated: July 24, 2020
• Results First Posted: July 24, 2020

Record last verified: 2020-07

Locations

US (1)