Efficacy of GXR as Adjunctive Therapy With Psycho-stimulant on Executive Function in Children With ADHD

NCT01985581 | Completed Phase 4 Results DMC

• 1 other identifier: RES 13-001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study looks to examine whether or not INTUNIV extended release can help children aged 6-12 years diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD) in improving Executive Function when added to their usual care stimulant therapy. Executive functions are a set of mental processes that include emotional control, planning, organization, working memory, inhibition of behaviors, and managing time and space. As children with ADHD usually have difficulties with Executive Function, and Executive function difficulties lead to more difficulties in school and behaviour, it is anticipated that adding INTUNIV extended release to usual stimulant therapy will improve Executive Function scores as rated by parents and teachers. Improvements in quality of life will also be measured.

Conditions

Attention Deficit Hyperactivity Disorder

Keywords

Attention Deficit Hyperactivity Disorder; Intuniv extended release; Executive Function; Quality of Life

Outcome Measures

Primary Outcomes (1)

• Effect of Adjunctive INTUNIV Extended Release Treatment on Executive Function as Assessed by Change From Baseline on the BRIEF-parent Questionnaires

  The Behavioural Rating Inventory of Executive Function (BRIEF) was developed to assess such real-world expressions of executive function in the home (BRIEF-P) as assessed by the parent. This is an 86 item questionnaire completed by the parents. The score is converted to a t-score with a score less than 65 being considered within the normal range. Higher scores are worsening in function.

  measured at baseline and end of each 12 week treament arm

Secondary Outcomes (6)

• Effect of Adjunctive INTUNIV Extended Release Treatment on Change in Quality of Life as Assessed by the KINDL®-Child Questionnaire.

  Measured at baseline and end of each 12 week treatment arm

• Effect of Adjunct Therapy on ADHD Symptom Control as Assessed by the Change in the ADHD Rating Scale (ADHD-RS-IV)

  comparison from baseline to end of each 12 week treatment arm

• Subjects Experiencing Suicidal Ideation, Suicidal Behaviour and Self-injurious Behaviour Without Suicidal Intent and Incident of Serious Adverse Events in Each Treatment Arm

  Measured up to 30 weeks

• Evaluate the Effect of Adjunctive INTUNIV Extended Release Treatment on Change in Quality of Life as Assessed by the KINDL®-Parent Questionnaire.

  Measured at baseline and end of each 12 week treatment arm

• Effect of Adjunct Therapy on ADHD Symptom Control as Assessed by the Change on the Clinical Global Impression of Severity (CGI-S) Scale

  comparison from baseline to end of each 12 week treatment arm

Study Arms (2)

Placebo first then GXR

EXPERIMENTAL

patient will continue to take stable dosage of usual stimulant therapy (Ritalin, Ritalin SR, Biphentin, Concerta, Vyvanse, Adderall or Dexedrine). In the first intervention period subject took placebo and second intervention period subject took GXR. GXR dose was optimized to between 1 and 4mg.

Drug: Guanfacine extended release; Drug: Placebo; Drug: Stimulant therapy

GXR first then Placebo

PLACEBO COMPARATOR

patient will continue to take stable dosage of usual stimulant(Ritalin, Ritalin SR, Biphentin, Concerta, Vyvanse, Adderall or Dexedrine). In the first intervention period subject took GXR and second intervention period subject took placebo. GXR dose was optimized to between 1 and 4mg.

Drug: Guanfacine extended release; Drug: Placebo; Drug: Stimulant therapy

Interventions

Guanfacine extended release DRUG

Also known as: Intuniv extended release

GXR first then Placebo; Placebo first then GXR

Placebo DRUG

GXR first then Placebo; Placebo first then GXR

Stimulant therapy DRUG

patient will continue to take stable dosage of usual stimulant therapy (Ritalin, Ritalin SR, Biphentin, Concerta, Vyvanse, Adderall or Dexedrine)

GXR first then Placebo; Placebo first then GXR

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female patient aged 6 to 12 years at the time of consent/assent and to then of study. A patient who would turn 13 before the end of the study cannot be enrolled
• Patient's parent or legally authorized representative (LAR) must provide signed informed consent before any study-related procedures are completed.
• Patient meets the diagnostic standard manual-5 criteria for a primary diagnosis of ADHD, combined sub-type, hyperactive/impulsive sub-type, or inattentive sub-type
• Patient is currently on a stable stimulant regimen but whose EF is suboptimal. Suboptimal EF is defined as a global executive composite t-score greater than 65 (\>1.5 SD from mean) on the BRIEF-P questionnaire at screening.
• Patient who is currently and is expected to remain on a stable stimulant regimen throughout the study. A stable stimulant regimen is defined as:
• No significant change in dose or dosing frequency within the past 30 days prior to screening and stimulant is felt to be optimized by the investigator.
• Patient is functioning at an age-appropriate level intellectually, as judged by the Investigator.
• Patient is able to swallow intact tablets.
• Patient has sitting blood pressure (BP) measurement within the 95th percentile for age, sex, and height (see Blood Pressure Levels for Boys and Girls by Age and Height Percentile
• Patient and parent/LAR understand, are willing, able, and likely to fully comply with the study procedures and restrictions defined in this protocol.

You may not qualify if:

• Patient has a current, controlled (requiring a prohibited medication or behavioural modification program) or uncontrolled, co-morbid psychiatric diagnosis \[except oppositional defiant disorder (ODD)\], including any severe co-morbid Axis II disorders or severe Axis I disorders such as post-traumatic stress disorder (PTSD), bipolar illness, psychosis, pervasive developmental disorder, obsessive-compulsive disorder (OCD), substance abuse disorder, or other symptomatic manifestations or lifetime history of bipolar illness, psychosis or conduct disorder.
• Patient has a known personal history, or presence, of structural cardiac abnormalities, cardiovascular or cerebrovascular disease, serious heart rhythm abnormalities, syncope, tachycardia, cardiac conduction problems (e.g., clinically significant heart block or QT interval prolongation: QTc \>0.44 seconds), exercise-related cardiac events including syncope and pre-syncope, or clinically significant bradycardia.
• Patient has a known family history (in siblings, parents, and/or grand-parents) of sudden cardiac death, ventricular arrhythmia, or QT prolongation (QTc \>0.44 seconds).
• Patient has a known history of hypertension (see Blood Pressure Levels for Boys and Girls by Age and Height Percentile
• Patient has glaucoma.
• Patient has a history of a seizure disorder (other than a simple childhood febrile seizure).
• Patient has renal or hepatic insufficiency
• Patient is currently using prohibited medication.
• Patient has taken another investigational product within 30 days prior to the Enrolment Visit.
• Patient has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride or any of its active ingredients or patient is taking other products containing guanfacine.
• History of adverse event or failure to respond (lack of efficacy) to an adequate trial of an alpha-agonist.
• Patient is female and is pregnant or currently lactating.
• Patient is currently considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt, or has a prior history of, or is currently demonstrating active suicide ideation. Patients with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the Investigator.

Sponsors & Collaborators

• JPM van Stralen Medicine Professional: lead

Study Sites (1)

JPM van Stralen Medicine Professional Corporation

Ottawa, Ontario, K2G1W2, Canada

Location

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Limitations and Caveats

There was insufficient teacher data collected to interpret the results. Children appeared to struggle with the completion of the KINDL calling in to question the validity of the results of this questionnaire

Results Point of Contact

• Title: Dr. Judy van Stralen
• Organization: Center for Pediatric Excellence

judyvanstralen@bellnet.ca

613-726-7355

Study Officials

• Judy PM van Stralen, MD

  JPM van Stralen Medicine Professinal Organization

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2013
• First Posted: November 15, 2013
• Study Start: October 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: May 23, 2016
• Results First Posted: May 23, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)