ADHDPhase 4NCT01709695
Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With ADHD
A Phase 4 study testing Guanfacine Hydrochloride XR in people with ADHD and Attention Deficit Hyperactivity Disorder, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
This study proposes to evaluate the effects of guanfacine extended release on brain activation during fMRI in children and adolescents with ADHD between the ages 8-15 and ADHD subjects randomized to placebo treatment. Read more about this study
- Who is it for?
- Ages 8 to 15 years
- Conditions the study is for
- ADHD, Attention Deficit Hyperactivity Disorder
- What is being tested?
- Guanfacine Hydrochloride XR
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2011to Dec 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Diagnosis of any subtype of ADHD
- Normal findings on physical exam, laboratory studies, vital signs, and ECG
- Weight = 60 kgs or less
- Able to complete study procedures and swallow capsules;
- Willing to commit to the entire visit schedule
- Off treatment or have been discontinued from their previous medication for two weeks.
Who cannot join
- Psychiatric comorbidity except Oppositional Defiant Disorder [ODD], Simple Phobia, and dysthymia (unless ongoing medication treatment is required);
- Currently a suicide risk, has previously made a suicide attempt or has a prior history of suicidal behavior;
- Has failed treatment with an adequate trial of an alpha-2 adrenergic agonist;
- Known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride.
- Children may not:
- be treated with systemic medication for a medical or psychiatric illness that have CNS effects or affect cognitive function;
Show all 19Show fewer
- have a known history or presence of structural cardiac abnormalities, exercise-related cardiac events, or clinically significant bradycardia;
- have orthostatic hypotension or a known history of hypertension;
- have an abnormal ECG that is deemed clinically significant;
- have a history of alcohol or other substance abuse or dependence within the last 6 months;
- use any medications that affect BP or heart rate (excluding the subject's current ADHD medication at screening);
- use another investigational medicinal product or participation in a clinical study within 30 days prior to the baseline visit;
- be significantly overweight based on Center for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts;
- have body weight of less than 25kg;
- have a clinically important abnormality on urine drug and alcohol screen (excluding the subject's current ADHD stimulant, if applicable);
- be female and currently pregnant or lactating;
- have symptoms indicative of a primary sleep disorder.
- have braces or other metal permanently placed within their body.
- be too anxious to tolerate the fMRI procedure, or be claustrophobic.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With Attention-deficit/Hyperactivity Disorder (ADHD): an Functional Magnetic Resonance Imaging(fMRI) Study of Brain Activation Pre and Post Treatment
This study proposes to evaluate the effects of guanfacine extended release on brain activation during fMRI in children and adolescents with ADHD between the ages 8-15 and ADHD subjects randomized to placebo treatment.
This study also proposes to collect DNA on study participants, to examine the genetic underpinning of the observed fMRI activation profiles at baseline and in response to treatment. The purpose is to examine polymorphisms of the adrenergic 2A gene (and other related targets) for genetic biomarkers in association with the fMRI findings of this study.
Read the detailed description
This study proposes to evaluate the effects of guanfacine on brain activation during fMRI in 12 children and adolescents ages 8 - 15 with ADHD treated with once-daily INTUNIV(TM) (guanfacine; GXR) extended release tablets and 12 ADHD subjects randomized to placebo treatment. Children will be comprehensively assessed using a variety of clinical and neuropsychological measures. They will be scanned at baseline while performing both the go/no-go task (a well validated task for measuring inhibitory control (Durston et al., 2002, 2003)) and the Stay Alert task - a new task designed to measure the arousal component of attention, which was used successfully in a recent fMRI study of guanfacine in healthy adults (Clerkin et al., 2009). They will then be treated with GXR or placebo for 6 - 8 weeks in accordance with titration and dosing strategies used in recent Phase III dose optimization trials (e.g., up to 4 mg/day), and re-scanned while performing the same two tasks. The fMRI scans will be conducted using a dedicated research 3.0 T Siemens scanner.
- Conditions
- ADHD, Attention Deficit Hyperactivity Disorder
- Being tested
- Guanfacine Hydrochloride XR, Placebo
- Keywords
- Intuniv, Attention Deficit Hyperactivity Disorder, fMRI
- 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.
Guanfacine Hydrochloride XRDrug
Also called INTUNIV non-stimulant medication, GXR
Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose
PlaceboDrug
Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose
| Study group | Role | What they receive |
|---|---|---|
| guanfacine hydrochloride XR | Experimental | Flexible dose titration of guanfacine extended release (Intuniv; active medication). The medication is titrated in doses from 1 - 4 mg once daily Receives: Drug: Guanfacine Hydrochloride XR |
| Placebo Group | Placebo comparator | Flexible dose titration of placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Go/No-go Task Performance Correct Inhibitions
Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.
Measured: Baseline and 8 weeks
Go/No-go Task Reaction Time
Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.
Measured: Baseline and 8 weeks
Go/No-go Task Performance Correct Responses
Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.
Measured: Baseline and 8 weeks
Secondary outcomes (6)
Clinical Global Impressions (CGI-I)
Clinical response was the Clinical Global Impression-Improvement scale (CGI-I). Lower CGI-I scores indicate greater improvement (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6= much worse; 7=very much worse.)
Measured: up to 8 weeks
Percentage Change in Atomoxetine Stimulant Side Effects Rating Scale (ASSERS)
Side effects rating scale. Assesses side effects known to occur in prior research using stimulant and non stimulant medications for treatment of ADHD. Scores range from 0 (not present) to 9 (severe side effects) and have been reported in aggregate as sum of severity responses on highest dose. This number is the sum of ASSERS, meaning it is the number and severity of side effects experienced. The percentage change in score from baseline.
Measured: up to 8 weeks
Finger Windows
Neuropsychological assessment: Finger Windows - a measure of spatial working memory. The participant shows memory of a demonstrated visual pattern. The examiner models a given sequence of windows and ask the participant to imitate the sequence by placing their finger through the same windows in the correct order. The total number of correct sequences achieved determines the level of performance.
Measured: Baseline
Digit Span
Neuropsychological assessment - Digit Span. The Digit Span test is either conducted verbally or using a computer program. A sequence of numbers is shown or read out to the participant. The participant is then told to repeat the numbers that were shown or read to them. This process continues until the participant can no longer remember either the full sequence of numbers or the correct order. This sequence is also continued until the participant makes an error. The Digit Span test is scored by the amount of numbers the participant was able to remember in each test. The scorer must add the total number of correct sequences, backwards and forwards. This test is also scored differently for a range of ages.
Measured: Baseline
Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV)
Norm referenced parent interview to assess severity and frequency of ADHD symptoms. Scores are reported as sums 0 (no symptoms) to 54 (severe).
Measured: baseline and 8 weeks
Continuous Performance Test - Commissions
Neuropsychological assessment - Continuous Performance Test - Commissions. CPT is a task-oriented computerized assessment of attention-related problems. Scores are compared with the normative scores for the age, group and gender of the person being tested. A t-score of 50 is equal to the mean, with higher values indicating more problematic behaviors and lower scores indicating less problematic behaviors.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2012 (estimated)
- Study startMar 2011
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ADHDStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeffrey Newcorn, Icahn School of Medicine at Mount Sinai
- Investigators
- Jeffrey Newcorn, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01709695
- Sponsor's protocol ID
- GCO 09-1825
- Other IDs
- HSM:10-00415
- Status last verified
- Jan 2018
- First submitted
- 30 Aug 2012
- Last updated
- 14 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bedard AC, Schulz KP, Krone B, Pedraza J, Duhoux S, Halperin JM, Newcorn JH. Neural mechanisms underlying the therapeutic actions of guanfacine treatment in youth with ADHD: a pilot fMRI study. Psychiatry Res. 2015 Mar 30;231(3):353-6. doi: 10.1016/j.pscychresns.2015.01.012. Epub 2015 Jan 19.
PubMed 25659477
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With Attention-deficit/Hyperactivity Disorder (ADHD): an Functional Magnetic Resonance Imaging(fMRI) Study of Brain Activation Pre and Post Treatment
- ClinicalTrials.gov ID
- NCT01709695
- Acronym / sponsor ID
- GCO 09-1825
- Conditions
- ADHD, Attention Deficit Hyperactivity Disorder
- Keywords
- Intuniv, Attention Deficit Hyperactivity Disorder, fMRI
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 18 Oct 2012 (estimated)
- Results
- Posted 14 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study proposes to evaluate the effects of guanfacine extended release on brain activation during fMRI in children and adolescents with ADHD between the ages 8-15 and ADHD subjects randomized to placebo treatment.
This study also proposes to collect DNA on study participants, to examine the genetic underpinning of the observed fMRI activation profiles at baseline and in response to treatment. The purpose is to examine polymorphisms of the adrenergic 2A gene (and other related targets) for genetic biomarkers in association with the fMRI findings of this study.
Detailed description
This study proposes to evaluate the effects of guanfacine on brain activation during fMRI in 12 children and adolescents ages 8 - 15 with ADHD treated with once-daily INTUNIV(TM) (guanfacine; GXR) extended release tablets and 12 ADHD subjects randomized to placebo treatment. Children will be comprehensively assessed using a variety of clinical and neuropsychological measures. They will be scanned at baseline while performing both the go/no-go task (a well validated task for measuring inhibitory control (Durston et al., 2002, 2003)) and the Stay Alert task - a new task designed to measure the arousal component of attention, which was used successfully in a recent fMRI study of guanfacine in healthy adults (Clerkin et al., 2009). They will then be treated with GXR or placebo for 6 - 8 weeks in accordance with titration and dosing strategies used in recent Phase III dose optimization trials (e.g., up to 4 mg/day), and re-scanned while performing the same two tasks. The fMRI scans will be conducted using a dedicated research 3.0 T Siemens scanner.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| guanfacine hydrochloride XR | Experimental | Drug: Guanfacine Hydrochloride XRFlexible dose titration of guanfacine extended release (Intuniv; active medication). The medication is titrated in doses from 1 - 4 mg once daily |
| Placebo Group | Placebo comparator | Drug: PlaceboFlexible dose titration of placebo |
Who may qualify
- Ages
- 8 to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Diagnosis of any subtype of ADHD
- Normal findings on physical exam, laboratory studies, vital signs, and ECG
- Weight = 60 kgs or less
- Able to complete study procedures and swallow capsules;
- Willing to commit to the entire visit schedule
Key exclusion criteria (19 listed)
- Psychiatric comorbidity except Oppositional Defiant Disorder [ODD], Simple Phobia, and dysthymia (unless ongoing medication treatment is required);
- Currently a suicide risk, has previously made a suicide attempt or has a prior history of suicidal behavior;
- Has failed treatment with an adequate trial of an alpha-2 adrenergic agonist;
- Known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride.
- be treated with systemic medication for a medical or psychiatric illness that have CNS effects or affect cognitive function;
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 |
|---|---|---|
| Guanfacine Hydrochloride XRAlso: INTUNIV non-stimulant medication, GXRWeekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose | Drug | guanfacine hydrochloride XR |
| PlaceboWeekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose | Drug | Placebo Group |
Primary outcome
Go/No-go Task Performance Correct Inhibitions
Time frame: Baseline and 8 weeks
Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.
Go/No-go Task Reaction Time
Time frame: Baseline and 8 weeks
Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.
Go/No-go Task Performance Correct Responses
Time frame: Baseline and 8 weeks
Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.
6 secondary outcomes
Clinical Global Impressions (CGI-I)
Time frame: up to 8 weeks
Percentage Change in Atomoxetine Stimulant Side Effects Rating Scale (ASSERS)
Time frame: up to 8 weeks
Finger Windows
Time frame: Baseline
Digit Span
Time frame: Baseline
Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV)
Time frame: baseline and 8 weeks
Continuous Performance Test - Commissions
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25659477Bedard AC, Schulz KP, Krone B, Pedraza J, Duhoux S, Halperin JM, Newcorn JH. Neural mechanisms underlying the therapeutic actions of guanfacine treatment in youth with ADHD: a pilot fMRI study. Psychiatry Res. 2015 Mar 30;231(3):353-6. doi: 10.1016/j.pscychresns.2015.01.012. Epub 2015 Jan 19.
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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.
Jeffrey Newcorn, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Guanfacine Hydrochloride XR in people with ADHD and Attention Deficit Hyperactivity Disorder, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
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 6 inclusion and 19 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 14 Feb 2018. 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 States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Go/No-go Task Performance Correct Inhibitions (time frame: Baseline and 8 weeks). The study lists 3 primary outcomes in all. 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 NCT01709695, which also lists 1 linked publication.
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 14 Feb 2018; AzTrials last refreshed its copy on 8 Nov 2026.