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| ID | Type | Description | Link |
|---|---|---|---|
| HSM:10-00415 |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Placebo Group | Placebo Comparator | Flexible dose titration of placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Guanfacine Hydrochloride XR | Drug | Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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. | Baseline and 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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.) | up to 8 weeks |
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Inclusion Criteria:
Exclusion Criteria:
Children may not:
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| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Newcorn, MD | Icahn School of Medicine at Mount Sinai | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25659477 | Result | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Guanfacine Hydrochloride XR | Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily |
| FG001 | Placebo Group | Flexible dose titration of placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Data unavailable for one participant in each group.
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| ID | Title | Description |
|---|---|---|
| BG000 | Guanfacine Hydrochloride XR | Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily |
| BG001 | Placebo Group | Flexible dose titration of placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | percentage correct inhibitions | Baseline and 8 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Guanfacine Hydrochloride XR | Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Somnolence | General disorders | ASSERS |
The small sample size in this pilot study limited power to detect large-sized effects.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Department of Psychiatry | Icahn School of Medicine at Mount Sinai | 212-241-6623 |
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| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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|
| Placebo | Drug | Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose |
|
| 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. |
| 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. | 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. | 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). | 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. | Baseline |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Full Scale IQ | Full Scale IQ - People who score generally between 70 and 130 are considered to be within the normal range of IQ functioning, where 100 is the theoretical average. Those scoring 130 and above have significantly greater cognitive resources than the average population, and those scoring 70 and below population have significantly fewer cognitive resources. | Mean | Standard Deviation | units on a scale |
|
| Attention-Deficit/Hyperactivity Disorder (ADHD) subtype | Count of Participants | Participants |
|
| Comorbid Oppositional Defiant Disorder (ODD) | Count of Participants | Participants |
|
| Clinical Global Impressions - Severity scale (CGI-S) | Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's symptoms at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of symptoms at the time of rating 1, normal, not at all ill; 2, minimally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, very servely ill. | Mean | Standard Deviation | units on a scale |
|
| Prior stimulant treatment | Count of Participants | Participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | ms | Baseline and 8 weeks |
|
|
|
| Secondary | 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.) | Posted | Mean | Standard Deviation | units on a scale | up to 8 weeks |
|
|
|
| Secondary | 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. | Posted | Number | percentage of mean effects improvement | up to 8 weeks |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | correct sequences | Baseline |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | correct sequences | Baseline |
|
|
|
| Secondary | 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). | Posted | Mean | Standard Deviation | units on a scale | baseline and 8 weeks |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | t-scores | Baseline |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | percentage correct responses | Baseline and 8 weeks |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 4 |
| 12 |
| EG001 | Placebo Group | Flexible dose titration of placebo | 0 | 13 | 0 | 13 | 3 | 13 |
| Dizziness | Nervous system disorders | ASSERS |
|
| Irritability | Psychiatric disorders | ASSERS |
|
| Increased Anxiety/Panic | Psychiatric disorders | ASSERS |
|
| Sleepiness | General disorders | ASSERS |
|
| Irritable and Moody | Psychiatric disorders | ASSERS |
|
| Difficulty Sleeping | General disorders | ASSERS |
|
| Viral Infection | Infections and infestations | ASSERS | Sore throat and nasal congestions secondary to common cold |
|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | ASSERS |
|
| Dizziness upon standing | General disorders | ASSERS |
|
| Drowsiness | General disorders | ASSERS |
|
| Appearing sedated | General disorders | ASSERS | could not tolerate dose rise, dose reduced |
|
| Aggression | General disorders | ASSERS |
|
| Tired | General disorders | ASSERS |
|
| Headache | General disorders | ASSERS |
|
| Weakness | General disorders | ASSERS | subjective feeling of weakness, without loss of strength. |
|
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| 8 weeks Reaction time (RT) |
|
| 8 weeks Reaction time standard deviation (RTSD) |
|