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
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Go/No-go Task Performance Correct Inhibitions
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 8 Years 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
guanfacine hydrochloride XR
Flexible dose titration of guanfacine extended release (Intuniv; active medication). The medication is titrated in doses from 1 - 4 mg once daily
干预措施: Guanfacine Hydrochloride XR (Drug)
Placebo Group
Flexible dose titration of placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Go/No-go Task Performance Correct Inhibitions
时间窗: 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.
Go/No-go Task Performance Correct Responses
时间窗: 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.
Go/No-go Task Reaction Time
时间窗: 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.
次要结局
- Clinical Global Impressions (CGI-I)(up to 8 weeks)
- Percentage Change in Atomoxetine Stimulant Side Effects Rating Scale (ASSERS)(up to 8 weeks)
- Finger Windows(Baseline)
- Digit Span(Baseline)
- Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV)(baseline and 8 weeks)
- Continuous Performance Test - Commissions(Baseline)
研究者
Jeffrey Newcorn
Principal Investigator
Icahn School of Medicine at Mount Sinai