Event Rate and Effects of Stimulants in ADHD

NCT01913912 | Withdrawn Phase 3

• 2 other identifiers: EC/2013/4812013-001530-18
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Stimulants alleviate information processing and task performance deficits in Attention Deficit/Hyperactivity Disorder (ADHD). Long acting formulations of amphetamines such as lisdexamphetamine dimesylate (LDX) are especially valuable as they target the school day and improve classroom performance. Although stimulants have been widely used in treatment of ADHD, the exact mechanism action and effect on task performance is not completely known. According to the State Regulation Deficit (SRD) model, children with ADHD have difficulty regulating their levels of arousal/activation during tasks in response to the changing demands of the environment. This leads to problems with downregulating overaroused states and upregulating underaroused states. According to this view, stimulants exert their therapeutic effect (in part) by optimising arousal/activation levels - especially during states of underarousal/activation. Arousal/activation levels can also be altered by extrinsic factors such as event rate (ER), e.g., the rate at which information is presented. Multiple studies suggest that very fast and very slow events can both cause problems for individuals with ADHD, related to overarousal and underarousal state respectively. Putting these intrinsic (stimulants) and extrinsic (ERs) factors together leads to the prediction that changing the rate at which information is presented in a task may alter the efficacy of stimulants and affect the optimal stimulant dose level. More specifically, one dose of stimulant that may be optimal on slow ER tasks (as it increases arousal/activation level) may be less effective under high ER tasks because in such a setting arousal/activation level needs to be lowered and not increased further. Adding stimulants to an already overactivated state may exacerbate the associated problems. The implication of this is that a different dose of stimulant will be needed under different environmental conditions for optimal performance. For example, children with ADHD might require different dosage in the classroom setting to optimize performance. In addition, the neuropsychological basis of performance deficits and improvement by ER and stimulants are also unclear. According to the SRD model, the underlying mechanism can be specific problems in motor activation/preparation or effort regulation. Event-related potentials (ERP), pupil size measurements and cardiac measures enable us to see objectively how motor activation/preparation and effort are affected by ER and simulants. In this study the investigators aim to test these predictions of the SRD model and identify the neurobiological basis of stimulant action.

Conditions

Attention Deficit Hyperactivity Disorder

Outcome Measures

Primary Outcomes (2)

• Performance data (by using computerized Go-No Go task)

  * mean reaction time (RT) * standard deviation of reaction time (SDRT) * errors of omissions (%EoO) * errors of commission (%EoC)

  2 weeks (week 8-9 of the study)

• psychophysiological data

  * cardiac indices: heart rate variability (HRV), heart rate deviation (HRD) (by using EEG) * electrophysiological indices: P3, LRP (lateralized readiness potential) (by using EEG) * pupil size (by using eye-tracking)

  2 weeks (week 8-9 of the study)

Study Arms (2)

Lisdexamfetamine dimesylate (LDX)

ACTIVE COMPARATOR

Children will continue their therapeutic dose of LDX during the DBPC phase (which is determined during the titration phase). Before each testing session there will be a washout period of at least 48 hours; the optimal dose of LDX will be given the morning of the testing at the DRUG unit. For blinding purpose we will blindfold the children when taking LDX at the DRUG unit.

Drug: LDX.; Device: computer task (Go/No-Go task); Device: EEG; Device: pupil size measurements (by using eye tracking)

Sugar pill

PLACEBO COMPARATOR

Children will continue their therapeutic dose of LDX during the DBPC phase (which is determined during the titration phase). Before each testing session there will be a washout period of at least 48 hours; the placebo will be given the morning of the testing at the DRUG unit. For blinding purpose we will blindfold the children when taking placebo at the DRUG unit.

Drug: sugar pill; Device: computer task (Go/No-Go task); Device: EEG; Device: pupil size measurements (by using eye tracking)

Interventions

LDX. DRUG

In this study 3 different doses of LDX will be used: * 30 mg capsules: 30 mg LDX, equivalent to 8.9 mg of dexamphetamine * 50 mg capsules: 50 mg LDX, equivalent to 14.8 mg of dexamphetamine * 70 mg capsules: 70 mg LDX, equivalent to 20.8 mg of dexamphetamine

Also known as: The European brandname is Elvance®

Lisdexamfetamine dimesylate (LDX)

sugar pill DRUG

Children will take once only a placebo capsule during the DBPC phase (phase 4) the morning of the testing. For blinding purpose we will blindfold the children when taking placebo.

Also known as: placebo

Sugar pill

computer task (Go/No-Go task) DEVICE

Lisdexamfetamine dimesylate (LDX); Sugar pill

EEG DEVICE

event-related potentials (ERP) and heart rate measurements

Lisdexamfetamine dimesylate (LDX); Sugar pill

pupil size measurements (by using eye tracking) DEVICE

Lisdexamfetamine dimesylate (LDX); Sugar pill

Eligibility Criteria

• Age: 7 Years - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Children with ADHD (male and female)
• Age: form 7 years old until the end of 12 years old at screening
• Official diagnosis of ADHD (one of the three subtypes) as confirmed by administration of the Diagnostic Interview Scale for Children for DSM-IV (DISC-IV) interview at screening
• No prior use of stimulant medication (Drug naïve)

You may not qualify if:

• Comorbid disorders (severe anxiety or mood disorder, Autism Spectrum Disorder, Conduct disorder, Tic disorder, other major psychiatric pathologies)
• Other neurological disorder or chronic illness/disability
• Intelligence quotient (IQ) below 80
• Body weight below 22.7 kg
• Use of a psychoactive medication (especially use of monoamine oxidase inhibitors (MAOI))
• History of cardiac disease, family history of premature (sudden/unexpected) death in children or young adults, hypertrophic cardiomyopathy, clinically important arrhythmias including long QT syndrome (LQTS), Marfan syndrome
• Abnormal findings on physical examination indicating cardiac disease
• Glaucoma
• Sensitive or allergic to stimulants or other ingredients of LDX

Sponsors & Collaborators

• University Ghent: lead
• Fund for Scientific Research, Flanders, Belgium: collaborator
• Shire: collaborator

Study Sites (2)

Ghent University Hospital

Ghent, 9000, Belgium

Location

Ghent University

Ghent, 9000, Belgium

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Sugars; Electroencephalography

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Carbohydrates; Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Study Officials

• Rudy van Coster, MD, PhD

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

• Herbert Roeyers, PhD

  University Ghent

  PRINCIPAL INVESTIGATOR

• Edmund Sonuga-Barke, PhD

  University Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2013
• First Posted: August 1, 2013
• Study Start: January 1, 2014
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: December 2, 2021

Record last verified: 2021-11

Locations

BE (2)