ADHDAGUALISNCT03333668
Experimental fMRI Study of Guanfacine and Lisdexamfetamine in ADHD Adolescents
A study testing Lisdexamfetamine dimesylate and Guanfacine Extended Release Oral Tablet in people with ADHD, run by King's College London at 1 site in United Kingdom.
Trial 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. The investigators will compare the brain activation changes elicited by Guanfacine extended release (GXR; a non-stimulant drug) with the brain activation changes… Read more about this study
- Who is it for?
- Ages 8 to 20 yearsHealthy volunteers can take part
- Conditions the study is for
- ADHD
- What is being tested?
- Lisdexamfetamine dimesylate and Guanfacine Extended Release Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Oct 2018to 7 Sep 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 20 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Institute of Psychiatry, Psychology & Neuroscience; King's College London
London, SE5 8AF
About this study
Official title: 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.
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. The investigators 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 the investigators intend to scan participants during their performance of tasks of attention, working memory, and inhibition, which the investigators know from previous studies to elicit abnormal brain activation patterns in ADHD patients (Rubia et al., 2005; Smith et al., 2006).
Read the detailed description
Twenty ADHD patients between 8 and 20 years of age 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 rounded down to the closest dose of 1mg, 2mg, or a maximum of 3mg), LISDEX (for participants aged 8-9 years 20mg regardless of weight; for participants aged 10-20 years the dose will be calculated at 0.5mg/kg rounded to the closest 30, 40, or 50mg, middle doses, e.g. 35mg, will be rounded down) and placebo (10mg Vit C) in one of the scans, in a randomised order. Patients will perform a battery of cognitive tests 3.5 hours after drug administration, after which the will undergo an fMRI scan. The scan will start 4.5 hours after drug administration where drugs have shown to have maximum plasma concentration. Participants will be scanned 3 times, one week apart, under each drug condition.
Substantial amendment submitted on 11/09/2019 regarding dosage:
Lowering the dose of lisdexamfetamine
The investigators had two participants who experienced transient minor adverse events after the single dose of Lisdexamfetamine.Therefore, the investigators have decided to lower the doses of lisdexamfetamine given in this study. Our original doses of lisdexamfetamine (30mg for participants under 30kg of body weight, 50mg for participants over 30kg of body weight) were weight adjusted and based on consultations with child psychiatrists, as well as on published studies using single doses of lisdexamfetamine. IN view of the adverse events our expert in paediatric psychopharmacology, Prof Paramala Santosh, has recommended the following rules for determining dosages of lisdexamfetamine in order to avoid any more adverse events:
- Ages 8-9 years - will receive 20mg (regardless of weight)
- Ages 10-20 years - will receive a minimum dose of 30mg or if higher than 60kg, a weight-adjusted dose at 0.5mg/kg which will be rounded down to the closest 30, 40, or 50mg (middle doses, e.g. 35mg, will be rounded down). The maximum dose will always be 50mg.
- Conditions
- ADHD
- Being tested
- Lisdexamfetamine dimesylate, Guanfacine Extended Release Oral Tablet, Placebo
- Keywords
- Lisdexamfetamine, Guanfacine, functional Magnetic Resonance Imaging, Attention Deficit Hyperactivity Disorder
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lisdexamfetamine dimesylateDrug
Also called Vyvanse (Shire Pharmaceuticals Ltd.)
Lisdexamfetamine dimesylate (30mg for smaller, 50mg for larger boys) tablet
Guanfacine Extended Release Oral TabletDrug
Also called Intuniv (Shire Pharmaceuticals Ltd.)
Guanfacine Extended Release (0.05mg/kg) tablet
PlaceboDrug
Vitamin C (10mg) tablet
| Study group | Role | What they receive |
|---|---|---|
| Lisdexamfetamine - Placebo | Active comparator | Not described Receives: Drug: Lisdexamfetamine dimesylate; Drug: Placebo |
| Guanfacine - Placebo | Active comparator | Not described Receives: Drug: Guanfacine Extended Release Oral Tablet; Drug: Placebo |
| Lisdexamfetamine - Guanfacine | Experimental | Not described Receives: Drug: Lisdexamfetamine dimesylate; Drug: Guanfacine Extended Release Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
- A working memory task (N-back)
- A tracking stop task
- A parametric sustained attention task
Measured: 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)
- A working memory task (N-back)
- A tracking stop task
- A parametric sustained attention task
Measured: 2 weeks (3 hourly scans one week apart)
Changes in dependent variables extracted from performance on a task battery outside the MRI scanner
Gonogo task, Simon task, Continuous performance task, Vigilance task, Time Discrimination task
Measured: 2 weeks (3 sessions one week apart)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2017
- Study start1 Oct 2018
- Primary completion6 Sep 2024
- Study completion7 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ADHDStudies of the same condition, open and under way.
- More trials run by King's College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Each participant will complete all three experimental conditions (LISDEX, GXR, placebo) in a randomised order.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Collaborators
- Shire, Takeda
- Responsible party
- Sponsor
- Investigators
- Katya Rubia, PhD, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03333668
- Sponsor's protocol ID
- PCCWUAR
- Acronym
- AGUALIS
- Status last verified
- Aug 2026
- First submitted
- 31 Oct 2017
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 15930054Smith 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.
PubMed 16741205El 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.
PubMed 41256939
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT03333668
- Acronym / sponsor ID
- AGUALIS / PCCWUAR
- Conditions
- ADHD
- Keywords
- Lisdexamfetamine, Guanfacine, functional Magnetic Resonance Imaging, Attention Deficit Hyperactivity Disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- Shire, Takeda
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- 6 Sep 2024 (actual)
- Study completion
- 7 Sep 2024 (actual)
- First posted
- 7 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. The investigators 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 the investigators intend to scan participants during their performance of tasks of attention, working memory, and inhibition, which the investigators 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 patients between 8 and 20 years of age 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 rounded down to the closest dose of 1mg, 2mg, or a maximum of 3mg), LISDEX (for participants aged 8-9 years 20mg regardless of weight; for participants aged 10-20 years the dose will be calculated at 0.5mg/kg rounded to the closest 30, 40, or 50mg, middle doses, e.g. 35mg, will be rounded down) and placebo (10mg Vit C) in one of the scans, in a randomised order. Patients will perform a battery of cognitive tests 3.5 hours after drug administration, after which the will undergo an fMRI scan. The scan will start 4.5 hours after drug administration where drugs have shown to have maximum plasma concentration. Participants will be scanned 3 times, one week apart, under each drug condition.
Substantial amendment submitted on 11/09/2019 regarding dosage:
Lowering the dose of lisdexamfetamine
The investigators had two participants who experienced transient minor adverse events after the single dose of Lisdexamfetamine.Therefore, the investigators have decided to lower the doses of lisdexamfetamine given in this study. Our original doses of lisdexamfetamine (30mg for participants under 30kg of body weight, 50mg for participants over 30kg of body weight) were weight adjusted and based on consultations with child psychiatrists, as well as on published studies using single doses of lisdexamfetamine. IN view of the adverse events our expert in paediatric psychopharmacology, Prof Paramala Santosh, has recommended the following rules for determining dosages of lisdexamfetamine in order to avoid any more adverse events:
- Ages 8-9 years - will receive 20mg (regardless of weight)
- Ages 10-20 years - will receive a minimum dose of 30mg or if higher than 60kg, a weight-adjusted dose at 0.5mg/kg which will be rounded down to the closest 30, 40, or 50mg (middle doses, e.g. 35mg, will be rounded down). The maximum dose will always be 50mg.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Each participant will complete all three experimental conditions (LISDEX, GXR, placebo) in a randomised order.
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 8 to 20 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lisdexamfetamine dimesylateAlso: Vyvanse (Shire Pharmaceuticals Ltd.)Lisdexamfetamine dimesylate (30mg for smaller, 50mg for larger boys) tablet | Drug | Lisdexamfetamine - Guanfacine, Lisdexamfetamine - Placebo |
| Guanfacine Extended Release Oral TabletAlso: Intuniv (Shire Pharmaceuticals Ltd.)Guanfacine Extended Release (0.05mg/kg) tablet | Drug | Guanfacine - Placebo, Lisdexamfetamine - Guanfacine |
| PlaceboVitamin C (10mg) tablet | Drug | Guanfacine - Placebo, Lisdexamfetamine - Placebo |
Primary outcome
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
2 secondary outcomes
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)
Changes in dependent variables extracted from performance on a task battery outside the MRI scanner
Time frame: 2 weeks (3 sessions one week apart)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Background: PubMed 15930054Rubia 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.
- Background: PubMed 16741205Smith 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.
- Derived from this study: PubMed 41256939El 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katya Rubia, PhD principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lisdexamfetamine dimesylate and Guanfacine Extended Release Oral Tablet in people with ADHD, run by King's College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in brain activation under the three drug conditions (LISDEX, GXR, placebo) (time frame: 2 weeks (3 hourly scans one week apart)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03333668, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.