Efficacy of GXR as Adjunctive Therapy With Psycho-stimulant on Executive Function in Children With ADHD
Condition: Attention Deficit Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: Guanfacine extended release; Placebo; Stimulant therapy
Intervention description: patient will continue to take stable dosage of usual stimulant therapy (Ritalin, Ritalin SR, Biphentin, Concerta, Vyvanse, Adderall or Dexedrine)
Intervention MeSH terms: Guanfacine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 50.0
Sex: All
Minimum age: 6 Years
Maximum age: 12 Years
Healthy volunteers: No
Keywords: Attention Deficit Hyperactivity Disorder; Intuniv extended release; Executive Function; Quality of Life

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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

          2. Patient's parent or legally authorized representative (LAR) must provide signed
             informed consent before any study-related procedures are completed.

          3. 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

          4. 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.

          5. 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.

          6. Patient is functioning at an age-appropriate level intellectually, as judged by the
             Investigator.

          7. Patient is able to swallow intact tablets.

          8. 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

          9. Patient and parent/LAR understand, are willing, able, and likely to fully comply with
             the study procedures and restrictions defined in this protocol.

        Exclusion Criteria:

          1. 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.

          2. Patient has any condition or illness which, in the opinion of the Investigator,
             represents an inappropriate risk to the patient and/or could confound the
             interpretation of the study. Mild stable asthma treated without the use of beta-2
             agonist is not exclusionary.

          3. 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.

          4. 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).

          5. Patient has a known history of hypertension (see Blood Pressure Levels for Boys and
             Girls by Age and Height Percentile

          6. Patient has glaucoma.

          7. Patient has a history of a seizure disorder (other than a simple childhood febrile
             seizure).

          8. Patient has renal or hepatic insufficiency

          9. Patient is currently using prohibited medication.

         10. Patient has taken another investigational product within 30 days prior to the
             Enrolment Visit.

         11. 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.

         12. History of adverse event or failure to respond (lack of efficacy) to an adequate trial
             of an alpha-agonist.

         13. Patient is female and is pregnant or currently lactating.

         14. 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.