Effect of Guanfacine Extended-Release on Attention Deficit Hyperactivity Disorder (ADHD)-Associated Insomnia

Study Overview
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Brief Summary
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This study seeks to determine, using special sleep tests (polysomnography and actigraphy) if guanfacine extended release is able to improve nighttime sleep in children with ADHD - associated insomnia while improving daytime ADHD symptoms. Male and female children with diagnosed or suspected ADHD with sleep problems (difficulty falling asleep, difficulty staying asleep, or less than expected hours of sleep) will be recruited. After obtaining informed consent and assent (when appropriate) and after discontinuation of excluded medications, children will have evaluations of his or her sleep and evaluations confirming the ADHD diagnosis. Children who successfully pass screening will be enrolled into the double-blind, placebo-controlled, randomized investigation with 50% of participants receiving guanfacine extended release and 50% of participants receiving matching placebo. Using a flexible-dose optimization design based on ADHD symptom improvement and medication tolerability, the dose will be adjusted between 1 to 4 mg over the course of four weeks. At the end of medication adjustment (week 4 or 5), ADHD questionnaires, sleep questionnaires, and sleep tests will be repeated and analyzed. The medication will be weaned over the course of the following 3-10 days.

Official Title
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Effect of Guanfacine Extended-Release on Attention Deficit Hyperactivity Disorder (ADHD)-Associated Insomnia

Conditions
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Attention Deficit Disorder, Insomnia, Sleep Disorders, Attention-Deficit/Hyperactivity Disorder

Intervention / Treatment
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* Drug: Guanfacine extended-release tablets
* Drug: Placebo comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be male or female, aged 6 - 12 years with ADHD. Subject must (a) be taking methylphenidate, amphetamine, or atomoxetine for treatment of ADHD with parent or subject concerns of inadequate efficacy or intolerable side effects, or (b) free of any other medication used to treat ADHD for at least 30 days at the time of the initial sleep study. Subject must have repeated difficulty with sleep initiation or persistence despite attempts at adequate sleep hygiene. Subject must be able to swallow tablets. Exclusion Criteria: Subject or parent/LAR is unable or unwilling to discontinue present medications used to treat ADHD. Subject has a body mass index < 5th percentile for age, using the Centers for Disease Control standards reported in 2000. Subject has a body weight > 176 pounds. Subject has a diagnosis of Autism or Autism Spectrum Disorder. Subject has other serious psychiatric diagnoses. Subject has a medical condition that may require treatment with an unapproved medication, that may cause a safety concern, or that may confound outcome results Subject has an excessive caffeine intake (greater than 2.5 mg/kg/d). Subject has a prior problem with clonidine or guanfacine.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Guanfacine Extended-Release Tablets<br>Guanfacine Extended-Release Tablets 1mg, 2mg, 3mg, and 4mg | Drug: Guanfacine extended-release tablets<br>* Guanfacine extended-release tablets will be started at 1mg and then increased at weekly intervals to 2mg, 3mg, or 4mg as needed and as tolerated<br>* Other names: Intuniv (TM), guanfacine HCl, SPD503;|
| Placebo Comparator: Placebo comparator<br>Placebo control | Drug: Placebo comparator<br>* Placebo tablets identical to the experimental arm guanfacine extended-release tablets 1mg, 2mg, 3mg, 4mg, but without the active ingredient (guanfacine).<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Polysomnographic Total Sleep Time (TST) | Change in objective measures of sleep, using polysomnography | Baseline to last observation carried forward (after at least one week of dose stability) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Baseline to Treatment ADHD-Rating Scale IV Total Score | Change in baseline to treatment ADHD-Rating Scale IV (Investigator-interview ) total. This scale quantitates ADHD symptoms based on DSM-IV criteria with a minimum score of 0 and a maximum score of 54 (higher scores suggesting more ADHD symptoms). The total score is a sum of the 9 items on the ADHD Rating Scale IV inattention score and the 9 items on the ADHD Rating Scale IV hyperactivity-impulsivity score (scores for each 0-27). | Baseline to last observation carried forward (after at least one week of dose stability) | 
| Change in Baseline to Treatment Latency to Persistent Sleep (LPS) | Change in an objective measure of sleep onset, using polysomnography. | Baseline to last observation carried forward (after at least one week of dose stability) | 
| Change in Baseline to Treatment Minutes of Wake Time After Sleep Onset (WASO) | Polysomnographic parameter of sleep assessing how many minutes of wakefulness occurred after sleep onset and before full morning awakening. | Baseline to last observation carried forward (after at least one week of dose stability) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD, ADD, sleep disturbance