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Experimental fMRI Study of Guanfacine and Lisdexamfetamine in ADHD Adolescents (AGUALIS)

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ClinicalTrials.gov Identifier: NCT03333668
Recruitment Status : Not yet recruiting
First Posted : November 7, 2017
Last Update Posted : November 7, 2017
Sponsor:
Collaborator:
Shire
Information provided by (Responsible Party):
King's College London

Tracking Information
First Submitted Date  ICMJE October 31, 2017
First Posted Date  ICMJE November 7, 2017
Last Update Posted Date November 7, 2017
Estimated Study Start Date  ICMJE March 1, 2018
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 3, 2017)
Change in brain activation under the three drug conditions (LISDEX, GXR, placebo) [ Time Frame: 2 weeks (3 hourly scans one week apart) ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2017)
Changes in dependent variables extracted from performance on the fMRI tasks used under the three drug conditions (LISDEX, GXR, placebo) [ Time Frame: 2 weeks (3 hourly scans one week apart) ]
  1. A working memory task (N-back)
  2. A tracking stop task
  3. A parametric sustained attention task
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Experimental fMRI Study of Guanfacine and Lisdexamfetamine in ADHD Adolescents
Official Title  ICMJE Experimental fMRI Study on the Comparison of the Brain Function Effects of a Single Dose of Guanfacine and Lisdexamfetamine Relative to Placebo in Children and Adolescents With ADHD.
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−naïve 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).
Detailed Description Twenty ADHD male patients between 10 and 18 years will participate in the double-blind, randomised, active drug condition, within-group, placebo-controlled experimental fMRI study. Each participant will be assessed in baseline measures during a pre-assessment visit. Then the patient will be scanned 3 times under each of these 3 drug conditions: GXR, LISDEX, and placebo. Every patient will receive a single typical clinical weight-adjusted dose of GXR (0.05mg/kg), LISDEX (30mg for smaller, 50mg for larger boys) and placebo (10mg Vit C) in one of the scans, in a randomised order. Patients will be scanned 4.5 hours after drug administration (where drugs have shown to have maximum plasma concentration). They will be scanned 3 times, one week apart, under each drug condition.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Each participant will complete all three experimental conditions (LISDEX, GXR, placebo) in a randomised order.
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE ADHD
Intervention  ICMJE
  • Drug: Lisdexamfetamine dimesylate
    Lisdexamfetamine dimesylate (30mg for smaller, 50mg for larger boys) tablet
    Other Name: Vyvanse (Shire Pharmaceuticals Ltd.)
  • Drug: Guanfacine Extended Release Oral Tablet
    Guanfacine Extended Release (0.05mg/kg) tablet
    Other Name: Intuniv (Shire Pharmaceuticals Ltd.)
  • Drug: Placebo
    Vitamin C (10mg) tablet
Study Arms  ICMJE
  • Active Comparator: Lisdexamfetamine - Placebo
    Interventions:
    • Drug: Lisdexamfetamine dimesylate
    • Drug: Placebo
  • Active Comparator: Guanfacine - Placebo
    Interventions:
    • Drug: Guanfacine Extended Release Oral Tablet
    • Drug: Placebo
  • Experimental: Lisdexamfetamine - Guanfacine
    Interventions:
    • Drug: Lisdexamfetamine dimesylate
    • Drug: Guanfacine Extended Release Oral Tablet
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: November 3, 2017)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age range: 10-18 years
  • Gender: male
  • Medication-naïve or on no medication for 2 or more years
  • Handedness: right-handed
  • Weight: 20-80 kg
  • 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 below clinical cut-off for ASD on the Social Communication Questionnaire (SCQ) (Rutter et al., 2003)
  • 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 > 80 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.

Exclusion Criteria:

  • IQ < 80 (Wechsler et al., 1999).
  • Comorbidity with schizophrenia, bipolar disorder, learning disability, autism, 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 10 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Olivia S Kowalczyk, BSc 02078480384 oliwia.s.kowalczyk@kcl.ac.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03333668
Other Study ID Numbers  ICMJE PCCWUAR
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party King's College London
Study Sponsor  ICMJE King's College London
Collaborators  ICMJE Shire
Investigators  ICMJE
Principal Investigator: Olivia S Kowalczyk, BSc IoPPN, King's College London
PRS Account King's College London
Verification Date October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP