Low-dose vs. Normal-dose Psychostimulants on Executive Functions in Individuals With ADHD

NCT02167048 | Active Not Recruiting Phase 1

• 1 other identifier: H14-00224
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This double-blind crossover study aims to compare cognitive performance (e.g., working memory, selective attention and cognitive flexibility) of children ages 6-18 years diagnosed with ADHD of the combined type (ADHD-C) or inattentive-type (ADHD-IA) and currently on \> 20 mg/day of psychostimulants (psychostimulants) on: a) their current dose of psychostimulants, vs. b) a lower-dose of psychostimulants (half of their current dose). The investigators hypothesize that the lower-dose psychostimulants will result in better cognitive performance than moderate-to-high doses of psychostimulants.

Conditions

Attention Deficit Hyperactivity Disorders

Keywords

Attention Deficit Hyperactivity Disorders; Executive Function; Methylphenidate; Psychostimulants; Adolescent; Child; Working Memory; Prefrontal Cortex; Attention; Cognitive Function; Inhibition

Outcome Measures

Primary Outcomes (2)

• Executive Functions (difference in performance on the two Psychostimulants doses)

  Executive Functions consist of selective attention, working memory, response inhibition, reasoning, and set switching. Each of those component abilities will be assessed, scores converted to z scores, and a composite score assigned to each subject for each test session.

  Day 1

• Executive Functions (difference in performance on the two Psychostimulant doses)

  Executive Functions consist of selective attention, working memory, response inhibition, reasoning, and set switching. Each of those component abilities will be assessed, scores converted to z scores, and a composite score assigned to each subject for each test session.

  2 weeks

Study Arms (3)

Normal-dose Psychostimulant, Low-dose

EXPERIMENTAL

Normal-dose: Dose participants are currently taking as part of their prescription (on more than or equals to 20 mg/day of Psychostimulants) Low-dose: Half the normal dose

Drug: Psychostimulants

Low-dose Psychostimulants, Normal-dose

ACTIVE COMPARATOR

Normal-dose: Dose participants are currently taking as part of their prescription (on more than or equals to 20 mg/day of Psychostimulants) Low-dose: Half the normal dose

Drug: Psychostimulants

No intervention, No intervention

NO INTERVENTION

This arm is completely no intervention, and is ONLY for healthy volunteers. We are testing healthy volunteers of the same age to give us an estimate of order effects to help us correct for better performance in the 2nd session due simply to taking the same tests twice (note: the tests are Version A and B).

Interventions

Psychostimulants DRUG

Participants will be tested twice 2 weeks apart. All will continue on their normal Psychostimulant dose up until 3 days before the testing day. 3 days before their 1st testing session, half the participants will start on either their current-dose of Psychostimulant or half their current dose depending on the arm they were randomized to (we provide those pills). To control for different pharmacokinetics of the Psychostimulant medications, a given participant will be tested at roughly the peak time for his/her specific version of Psychostimulant and at the same time of day for his/her two testing sessions.

Low-dose Psychostimulants, Normal-dose; Normal-dose Psychostimulant, Low-dose

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Between the chronological ages of 6 and 18 years
• Average to above-average IQ (Parental report of an IQ above 90; we will take their word for it)
• Meet DSM-V criteria for ADHD (Combined type or Inattentive type)
• Currently treated with and responding to oral Psychostimulants \>= 20 mg/day and not on a "drug holiday"
• Stable on current Psychostimulant dose for at least 2 weeks
• Able to communicate (understand, speak, and write) in English without the aid of an interpreter
• Able to execute simple manual response (button-press) as required for our tasks
• The child and parent give assent and consent respectively for the child's participation in this study

You may not qualify if:

• Patients with significant prior or current medical conditions that could impact neuropsychological performance such as traumatic brain injury, hypoxia, or unstable diabetes.
• Have any medical condition that could markedly increase sympathetic nervous system activity (e.g. catecholamine-secreting neural tumor), or who are taking a medication on a daily basis (e.g. pseudoephedrine, oral steroids) that has sympathomimetic activity. Note: regular on-label use of inhalers for asthma (e.g., albuterol, steroidal) is permitted
• Taking any psychotropic medication other than on-label Psychostimulants specifically prescribed to treat ADHD
• Have a major, uncorrected sensory impairment (e.g. significant hearing impairment despite hearing aids)
• Lack sufficient English language skills to perform our tasks
• Are taking medications other than their specifically prescribed Psychostimulants that may affect cognitive skills
• Have a documented history of Dyslexia (this may skew results on our cognitive measures), Bipolar I or II, psychosis, Depression, Autism Spectrum Disorders, or Disruptive Mood Dysregulation Disorder
• Have a past history of any severe adverse reaction to lowering of Psychostiumlant dose
• Patient has been non-compliant with Psychostimulants or is on a "drug holiday"
• Parental report of an IQ below 90 (we will take their word for it)

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

Developmental Cognitive Neuroscience Lab, Department of Psychiatry, University of British Columbia

Vancouver, British Columbia, V6T 2A1, Canada

Location

Related Publications (8)

• Barkley RA. Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychol Bull. 1997 Jan;121(1):65-94. doi: 10.1037/0033-2909.121.1.65.

  PMID: 9000892 BACKGROUND

• Diamond A. Executive functions. Annu Rev Psychol. 2013;64:135-68. doi: 10.1146/annurev-psych-113011-143750. Epub 2012 Sep 27.

  PMID: 23020641 BACKGROUND

• Jacques, S., & Marcovitch, S. (2010). Development of executive function across the life span. In W. F. Overton (Ed.), Cognition, biology and methods across the lifespan: Volume 1 of the handbook of life-span development (pp. 431-466). Hoboken, NJ: Wiley.

  BACKGROUND

• Jucaite A, Fernell E, Halldin C, Forssberg H, Farde L. Reduced midbrain dopamine transporter binding in male adolescents with attention-deficit/hyperactivity disorder: association between striatal dopamine markers and motor hyperactivity. Biol Psychiatry. 2005 Feb 1;57(3):229-38. doi: 10.1016/j.biopsych.2004.11.009.

  PMID: 15691523 BACKGROUND

• Waldman ID, Rowe DC, Abramowitz A, Kozel ST, Mohr JH, Sherman SL, Cleveland HH, Sanders ML, Gard JM, Stever C. Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: heterogeneity owing to diagnostic subtype and severity. Am J Hum Genet. 1998 Dec;63(6):1767-76. doi: 10.1086/302132.

  PMID: 9837830 BACKGROUND

• Berridge CW, Devilbiss DM, Andrzejewski ME, Arnsten AF, Kelley AE, Schmeichel B, Hamilton C, Spencer RC. Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry. 2006 Nov 15;60(10):1111-20. doi: 10.1016/j.biopsych.2006.04.022. Epub 2006 Jun 23.

  PMID: 16806100 BACKGROUND

• Schmeichel BE, Berridge CW. Neurocircuitry underlying the preferential sensitivity of prefrontal catecholamines to low-dose psychostimulants. Neuropsychopharmacology. 2013 May;38(6):1078-84. doi: 10.1038/npp.2013.6. Epub 2013 Feb 6.

  PMID: 23303075 BACKGROUND

• Spencer RC, Klein RM, Berridge CW. Psychostimulants act within the prefrontal cortex to improve cognitive function. Biol Psychiatry. 2012 Aug 1;72(3):221-7. doi: 10.1016/j.biopsych.2011.12.002. Epub 2011 Dec 29.

  PMID: 22209638 BACKGROUND

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity; Inhibition, Psychological

Condition Hierarchy (Ancestors)

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

Study Officials

• Adele Diamond, Ph.D.

  Department of Psychiatry, University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 11, 2014
• First Posted: June 18, 2014
• Study Start: June 1, 2014
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

CA (1)