Back to resultsNeurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With ADHD
Primary Purpose
ADHD, Attention Deficit Hyperactivity Disorder
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Guanfacine Hydrochloride XR
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for ADHD focused on measuring Intuniv, Attention Deficit Hyperactivity Disorder, fMRI
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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;
- 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.
Sites / Locations
- Icahn School of Medicine at Mount Sinai
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
guanfacine hydrochloride XR
Placebo Group
Arm Description
Flexible dose titration of guanfacine extended release (Intuniv; active medication). The medication is titrated in doses from 1 - 4 mg once daily
Flexible dose titration of placebo
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.)
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.
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.
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.
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).
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.
Full Information
NCT ID
NCT01709695
First Posted
August 30, 2012
Last Updated
January 17, 2018
Sponsor
Icahn School of Medicine at Mount Sinai
1. Study Identification
Unique Protocol Identification Number
NCT01709695
Brief Title
Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With ADHD
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ADHD, Attention Deficit Hyperactivity Disorder
Keywords
Intuniv, Attention Deficit Hyperactivity Disorder, fMRI
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
guanfacine hydrochloride XR
Arm Type
Experimental
Arm Description
Flexible dose titration of guanfacine extended release (Intuniv; active medication). The medication is titrated in doses from 1 - 4 mg once daily
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
Flexible dose titration of placebo
Intervention Type
Drug
Intervention Name(s)
Guanfacine Hydrochloride XR
Other Intervention Name(s)
INTUNIV non-stimulant medication, GXR
Intervention Description
Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose
Primary Outcome Measure Information:
Title
Go/No-go Task Performance Correct Inhibitions
Description
Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.
Time Frame
Baseline and 8 weeks
Title
Go/No-go Task Reaction Time
Description
Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.
Time Frame
Baseline and 8 weeks
Title
Go/No-go Task Performance Correct Responses
Description
Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.
Time Frame
Baseline and 8 weeks
Secondary Outcome Measure Information:
Title
Clinical Global Impressions (CGI-I)
Description
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.)
Time Frame
up to 8 weeks
Title
Percentage Change in Atomoxetine Stimulant Side Effects Rating Scale (ASSERS)
Description
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.
Time Frame
up to 8 weeks
Title
Finger Windows
Description
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.
Time Frame
Baseline
Title
Digit Span
Description
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.
Time Frame
Baseline
Title
Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV)
Description
Norm referenced parent interview to assess severity and frequency of ADHD symptoms. Scores are reported as sums 0 (no symptoms) to 54 (severe).
Time Frame
baseline and 8 weeks
Title
Continuous Performance Test - Commissions
Description
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.
Time Frame
Baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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;
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Newcorn, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
25659477
Citation
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.
Results Reference
result
Learn more about this trial
Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With ADHD
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