Trial Outcomes & Findings for Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With ADHD (NCT NCT01709695)

NCT ID: NCT01709695

Last Updated: 2018-02-14

Results Overview

Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 27 participants
• Primary outcome timeframe: Baseline and 8 weeks
• Results posted on: 2018-02-14

Participant Flow

Participant milestones

Measure	Guanfacine Hydrochloride XR Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group Flexible dose titration of placebo
Overall Study STARTED	13	14
Overall Study COMPLETED	12	13
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Guanfacine Hydrochloride XR Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group Flexible dose titration of placebo
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With ADHD

Baseline characteristics by cohort

Measure	Guanfacine Hydrochloride XR n=12 Participants Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group n=13 Participants Flexible dose titration of placebo	Total n=25 Participants Total of all reporting groups
Age, Continuous	10.6 years STANDARD_DEVIATION 1.7 • n=5 Participants	11.5 years STANDARD_DEVIATION 2.5 • n=7 Participants	11.1 years STANDARD_DEVIATION 2.2 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Full Scale IQ	110.0 units on a scale STANDARD_DEVIATION 21.6 • n=5 Participants	101.8 units on a scale STANDARD_DEVIATION 13.1 • n=7 Participants	105.7 units on a scale STANDARD_DEVIATION 17.75 • n=5 Participants
Attention-Deficit/Hyperactivity Disorder (ADHD) subtype Combined	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Attention-Deficit/Hyperactivity Disorder (ADHD) subtype Inattentive	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Comorbid Oppositional Defiant Disorder (ODD)	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Clinical Global Impressions - Severity scale (CGI-S)	4.9 units on a scale STANDARD_DEVIATION 1.0 • n=5 Participants	5.4 units on a scale STANDARD_DEVIATION 0.9 • n=7 Participants	5.2 units on a scale STANDARD_DEVIATION 0.9 • n=5 Participants
Prior stimulant treatment	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Guanfacine Hydrochloride XR n=12 Participants Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group n=13 Participants Flexible dose titration of placebo
Go/No-go Task Performance Correct Inhibitions Baseline Correct inhibitions	91 percentage correct inhibitions Standard Deviation 8	89 percentage correct inhibitions Standard Deviation 10
Go/No-go Task Performance Correct Inhibitions 8 Weeks Correct inhibitions	94 percentage correct inhibitions Standard Deviation 6	92 percentage correct inhibitions Standard Deviation 7

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Guanfacine Hydrochloride XR n=12 Participants Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group n=13 Participants Flexible dose titration of placebo
Go/No-go Task Reaction Time Baseline Reaction time (RT)	572 ms Standard Deviation 144	543 ms Standard Deviation 99
Go/No-go Task Reaction Time Baseline Reaction time standard deviation (RTSD)	187 ms Standard Deviation 109	165 ms Standard Deviation 76
Go/No-go Task Reaction Time 8 weeks Reaction time (RT)	562 ms Standard Deviation 106	550 ms Standard Deviation 107
Go/No-go Task Reaction Time 8 weeks Reaction time standard deviation (RTSD)	184 ms Standard Deviation 93	166 ms Standard Deviation 73

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Guanfacine Hydrochloride XR n=12 Participants Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group n=13 Participants Flexible dose titration of placebo
Go/No-go Task Performance Correct Responses Baseline Correct responses	76 percentage correct responses Standard Deviation 18	75 percentage correct responses Standard Deviation 14
Go/No-go Task Performance Correct Responses 8 Weeks Correct responses	79 percentage correct responses Standard Deviation 15	74 percentage correct responses Standard Deviation 15

SECONDARY outcome

Timeframe: up to 8 weeks

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.)

Outcome measures

Measure	Guanfacine Hydrochloride XR n=12 Participants Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group n=13 Participants Flexible dose titration of placebo
Clinical Global Impressions (CGI-I)	2.0 units on a scale Standard Deviation 0.7	2.9 units on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: up to 8 weeks

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.

Outcome measures

Measure	Guanfacine Hydrochloride XR n=12 Participants Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group n=13 Participants Flexible dose titration of placebo
Percentage Change in Atomoxetine Stimulant Side Effects Rating Scale (ASSERS)	78 percentage of mean effects improvement	65.18 percentage of mean effects improvement

SECONDARY outcome

Timeframe: Baseline

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.

Outcome measures

Measure	Guanfacine Hydrochloride XR n=12 Participants Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group n=13 Participants Flexible dose titration of placebo
Finger Windows Finger Windows - F	12.5 correct sequences Standard Deviation 6.52	10.75 correct sequences Standard Deviation 4.63
Finger Windows Finger Windows -B	11.35 correct sequences Standard Deviation 5.45	8.00 correct sequences Standard Deviation 5.14

SECONDARY outcome

Timeframe: Baseline

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.

Outcome measures

Measure	Guanfacine Hydrochloride XR n=12 Participants Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group n=13 Participants Flexible dose titration of placebo
Digit Span Digit Span - F	6.92 correct sequences Standard Deviation 1.73	7.54 correct sequences Standard Deviation 2.54
Digit Span Digit Span - B	48.62 correct sequences Standard Deviation 8.76	48.62 correct sequences Standard Deviation 8.76

SECONDARY outcome

Timeframe: baseline and 8 weeks

Norm referenced parent interview to assess severity and frequency of ADHD symptoms. Scores are reported as sums 0 (no symptoms) to 54 (severe).

Outcome measures

Measure	Guanfacine Hydrochloride XR n=12 Participants Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group n=13 Participants Flexible dose titration of placebo
Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV) Baseline	36.67 units on a scale Standard Deviation 9.01	39.15 units on a scale Standard Deviation 9.08
Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV) End of treatment at 8 weeks	9.42 units on a scale Standard Deviation 6.96	22.69 units on a scale Standard Deviation 11.90

SECONDARY outcome

Timeframe: Baseline

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.

Outcome measures

Measure	Guanfacine Hydrochloride XR n=12 Participants Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group n=13 Participants Flexible dose titration of placebo
Continuous Performance Test - Commissions	48.62 t-scores Standard Deviation 3.81	46.99 t-scores Standard Deviation 2.99

Adverse Events

Guanfacine Hydrochloride XR

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo Group

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Guanfacine Hydrochloride XR n=12 participants at risk Flexible dose titration of guanfacine extended release - titrated in doses from 1 - 4 mg once daily	Placebo Group n=13 participants at risk Flexible dose titration of placebo
General disorders Somnolence	0.00% 0/12	7.7% 1/13
Nervous system disorders Dizziness	0.00% 0/12	7.7% 1/13
Psychiatric disorders Irritability	8.3% 1/12	7.7% 1/13
Psychiatric disorders Increased Anxiety/Panic	0.00% 0/12	7.7% 1/13
General disorders Sleepiness	16.7% 2/12	15.4% 2/13
Psychiatric disorders Irritable and Moody	0.00% 0/12	15.4% 2/13
General disorders Difficulty Sleeping	0.00% 0/12	7.7% 1/13
Infections and infestations Viral Infection	0.00% 0/12	7.7% 1/13
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/12	7.7% 1/13
General disorders Dizziness upon standing	8.3% 1/12	0.00% 0/13
General disorders Drowsiness	25.0% 3/12	0.00% 0/13
General disorders Appearing sedated	8.3% 1/12	0.00% 0/13
General disorders Aggression	8.3% 1/12	0.00% 0/13
General disorders Tired	8.3% 1/12	0.00% 0/13
General disorders Headache	8.3% 1/12	0.00% 0/13
General disorders Weakness	8.3% 1/12	0.00% 0/13

Additional Information

Department of Psychiatry

Icahn School of Medicine at Mount Sinai

Phone: 212-241-6623

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place