Event Rate and Effects of Stimulants in ADHD

• Status: Unknown status
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University Ghent
• Collaborators: Fund for Scientific Research, Flanders, Belgium; Shire
• Treatments: Central Nervous System Stimulants

Criteria

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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