Experimental fMRI Study of Guanfacine and Lisdexamfetamine in ADHD Adolescents

NCT03333668 | Unknown

• 1 other identifier: PCCWUAR
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is not a clinical trial. The aim of this study is to understand the mechanism of action of two recently licensed drugs for ADHD on brain function. We will compare the brain activation changes elicited by Guanfacine extended release (GXR; a non-stimulant drug) with the brain activation changes elicited by Lisdexamfetamine (LISDEX; a stimulant drug) and by placebo in 20 drug-free patients with ADHD using functional Magnetic Resonance Imaging (fMRI). For this purpose we intend to scan participants during their performance of tasks of attention, working memory, and inhibition, which we know from previous studies to elicit abnormal brain activation patterns in ADHD patients (Rubia et al., 2005; Smith et al., 2006).

Conditions

ADHD

Keywords

Lisdexamfetamine; Guanfacine; functional Magnetic Resonance Imaging; Attention Deficit Hyperactivity Disorder

Outcome Measures

Primary Outcomes (1)

• Change in brain activation under the three drug conditions (LISDEX, GXR, placebo)

  Brain activation as measured by blood-oxygen-level-dependent (BOLD) response obtained by fMRI for each of the 3 below listed tasks and functional connectivity measures for the resting state scan. 1. A working memory task (N-back) 2. A tracking stop task 3. A parametric sustained attention task

  2 weeks (3 hourly scans one week apart)

Secondary Outcomes (2)

• Changes in dependent variables extracted from performance on the fMRI tasks used under the three drug conditions (LISDEX, GXR, placebo)

  2 weeks (3 hourly scans one week apart)

• Changes in dependent variables extracted from performance on a task battery outside the MRI scanner

  2 weeks (3 sessions one week apart)

Study Arms (3)

Lisdexamfetamine - Placebo

ACTIVE COMPARATOR

Drug: Lisdexamfetamine dimesylate; Drug: Placebo

Guanfacine - Placebo

ACTIVE COMPARATOR

Drug: Guanfacine Extended Release Oral Tablet; Drug: Placebo

Lisdexamfetamine - Guanfacine

EXPERIMENTAL

Drug: Lisdexamfetamine dimesylate; Drug: Guanfacine Extended Release Oral Tablet

Interventions

Lisdexamfetamine dimesylate DRUG

Lisdexamfetamine dimesylate (30mg for smaller, 50mg for larger boys) tablet

Also known as: Vyvanse (Shire Pharmaceuticals Ltd.)

Lisdexamfetamine - Guanfacine; Lisdexamfetamine - Placebo

Guanfacine Extended Release Oral Tablet DRUG

Guanfacine Extended Release (0.05mg/kg) tablet

Also known as: Intuniv (Shire Pharmaceuticals Ltd.)

Guanfacine - Placebo; Lisdexamfetamine - Guanfacine

Placebo DRUG

Vitamin C (10mg) tablet

Guanfacine - Placebo; Lisdexamfetamine - Placebo

Eligibility Criteria

• Age: 8 Years - 20 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age range: 8-20 years
• Medication-naïve or non-medicated for two weeks or on stimulant medication, and willing to take the medication off for 48 hours before scans.
• Meeting DSM-5 diagnosis of ADHD
• Score above clinical cut-off on the ADHD module of the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) (Kaufman et al., 1997)
• Score above clinical cut-off for ADHD on the short forms of the Conners Parent Rating Scales, CPRS (Conners et al., 2008)
• Score above cut-off on the ADHD Rating Scale, ADHD-RS (DuPaul, et al., 1998)
• IQ \> 70 as tested on the WASI-II (Wechsler et al., 1999)
• Mood and depression symptoms will be allowed as long as they are not the primary diagnosis.

You may not qualify if:

• IQ \< 70 (Wechsler et al., 1999).
• Comorbidity with schizophrenia, bipolar disorder, learning disability, OCD, severe depression with current suicidal behaviour (as assessed by a clinical interview)
• Neurological problems, i.e. a history of severe neurological illness, e.g. brain tumour, epilepsy or a history of symptomatic seizures, polyneuropathy etc.
• Substance abuse history
• Other illness (cardiovascular, renal, hepatic, metabolic) that would impact the data integrity or safety of the subject (i.e. contraindicated to any of the treatments) as determined by the investigators
• Contraindication to MRI. i.e., previous implantation of metallic material, pacemaker, implanted medication pumps, neural stimulators, claustrophobia
• Unable to give informed assent or consent in the case of the parent
• Contraindications for LISDEX and GXR use (i.e. advanced arteriosclerosis, agitated states, hyperexcitability, hyperthyroidism, moderate or severe hypertension, symptomatic cardiovascular disease)

Sponsors & Collaborators

• King's College London: lead
• Shire: collaborator

Study Sites (1)

Institute of Psychiatry, Psychology & Neuroscience; King's College London

London, SE5 8AF, United Kingdom

Location

Related Publications (3)

• Rubia K, Smith AB, Brammer MJ, Toone B, Taylor E. Abnormal brain activation during inhibition and error detection in medication-naive adolescents with ADHD. Am J Psychiatry. 2005 Jun;162(6):1067-75. doi: 10.1176/appi.ajp.162.6.1067.

  PMID: 15930054 BACKGROUND

• Smith AB, Taylor E, Brammer M, Toone B, Rubia K. Task-specific hypoactivation in prefrontal and temporoparietal brain regions during motor inhibition and task switching in medication-naive children and adolescents with attention deficit hyperactivity disorder. Am J Psychiatry. 2006 Jun;163(6):1044-51. doi: 10.1176/ajp.2006.163.6.1044.

  PMID: 16741205 BACKGROUND

• El Masri S, Kowalczyk OS, Chiu TH, Criaud M, Lukito S, Mazibuko N, Salazar de Pablo G, Perez Rodriguez V, Makos O, Lam SL, Westwood S, Eaton-Turner A, Bozhilova N, Conti A, Santosh P, Roessner V, Kohls G, Mehta MA, Rubia K. Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD. Front Psychiatry. 2025 Nov 3;16:1676472. doi: 10.3389/fpsyt.2025.1676472. eCollection 2025.

  PMID: 41256939 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Lisdexamfetamine Dimesylate; Guanfacine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dextroamphetamine; Amphetamine; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Guanidines; Amidines; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids

Study Officials

• Katya Rubia, PhD

  King's College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each participant will complete all three experimental conditions (LISDEX, GXR, placebo) in a randomised order.

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: November 7, 2017
• Study Start: October 1, 2018
• Primary Completion: December 31, 2022
• Study Completion: March 31, 2025
• Last Updated: August 17, 2022

Record last verified: 2022-08

Locations

GB (1)