Experimental fMRI Study on the Comparison of the Brain Function Effects of a Single Dose of Guanfacine and Lisdexamfetamine Relative to Placebo in Children and Adolescents With ADHD.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Change in brain activation under the three drug conditions (LISDEX, GXR, placebo)
研究概览
简要总结
This is not a clinical trial. The aim of this study is to understand the mechanism of action of two recently licensed drugs for ADHD on brain function. The investigators will compare the brain activation changes elicited by Guanfacine extended release (GXR; a non-stimulant drug) with the brain activation changes elicited by Lisdexamfetamine (LISDEX; a stimulant drug) and by placebo in 20 drug-free patients with ADHD using functional Magnetic Resonance Imaging (fMRI). For this purpose the investigators intend to scan participants during their performance of tasks of attention, working memory, and inhibition, which the investigators know from previous studies to elicit abnormal brain activation patterns in ADHD patients (Rubia et al., 2005; Smith et al., 2006).
详细描述
Twenty ADHD patients between 8 and 20 years of age will participate in the double-blind, randomised, active drug condition, within-group, placebo-controlled experimental fMRI study. Each participant will be assessed in baseline measures during a pre-assessment visit. Then the patient will be scanned 3 times under each of these 3 drug conditions: GXR, LISDEX, and placebo. Every patient will receive a single typical clinical weight-adjusted dose of GXR (0.05mg/kg rounded down to the closest dose of 1mg, 2mg, or a maximum of 3mg), LISDEX (for participants aged 8-9 years 20mg regardless of weight; for participants aged 10-20 years the dose will be calculated at 0.5mg/kg rounded to the closest 30, 40, or 50mg, middle doses, e.g. 35mg, will be rounded down) and placebo (10mg Vit C) in one of the scans, in a randomised order. Patients will perform a battery of cognitive tests 3.5 hours after drug administration, after which the will undergo an fMRI scan. The scan will start 4.5 hours after drug administration where drugs have shown to have maximum plasma concentration. Participants will be scanned 3 times, one week apart, under each drug condition.
Substantial amendment submitted on 11/09/2019 regarding dosage:
Lowering the dose of lisdexamfetamine
The investigators had two participants who experienced transient minor adverse events after the single dose of Lisdexamfetamine.Therefore, the investigators have decided to lower the doses of lisdexamfetamine given in this study. Our original doses of lisdexamfetamine (30mg for participants under 30kg of body weight, 50mg for participants over 30kg of body weight) were weight adjusted and based on consultations with child psychiatrists, as well as on published studies using single doses of lisdexamfetamine. IN view of the adverse events our expert in paediatric psychopharmacology, Prof Paramala Santosh, has recommended the following rules for determining dosages of lisdexamfetamine in order to avoid any more adverse events:
- Ages 8-9 years - will receive 20mg (regardless of weight)
- Ages 10-20 years - will receive a minimum dose of 30mg or if higher than 60kg, a weight-adjusted dose at 0.5mg/kg which will be rounded down to the closest 30, 40, or 50mg (middle doses, e.g. 35mg, will be rounded down). The maximum dose will always be 50mg.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 8 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age range: 8-20 years
- •Medication-naïve or non-medicated for two weeks or on stimulant medication, and willing to take the medication off for 48 hours before scans.
- •Meeting DSM-5 diagnosis of ADHD
- •Score above clinical cut-off on the ADHD module of the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) (Kaufman et al., 1997)
- •Score above clinical cut-off for ADHD on the short forms of the Conners Parent Rating Scales, CPRS (Conners et al., 2008)
- •Score above cut-off on the ADHD Rating Scale, ADHD-RS (DuPaul, et al., 1998)
- •IQ > 70 as tested on the WASI-II (Wechsler et al., 1999)
- •Mood and depression symptoms will be allowed as long as they are not the primary diagnosis.
排除标准
- •IQ < 70 (Wechsler et al., 1999).
- •Comorbidity with schizophrenia, bipolar disorder, learning disability, OCD, severe depression with current suicidal behaviour (as assessed by a clinical interview)
- •Neurological problems, i.e. a history of severe neurological illness, e.g. brain tumour, epilepsy or a history of symptomatic seizures, polyneuropathy etc.
- •Substance abuse history
- •Other illness (cardiovascular, renal, hepatic, metabolic) that would impact the data integrity or safety of the subject (i.e. contraindicated to any of the treatments) as determined by the investigators
- •Contraindication to MRI. i.e., previous implantation of metallic material, pacemaker, implanted medication pumps, neural stimulators, claustrophobia
- •Unable to give informed assent or consent in the case of the parent
- •Contraindications for LISDEX and GXR use (i.e. advanced arteriosclerosis, agitated states, hyperexcitability, hyperthyroidism, moderate or severe hypertension, symptomatic cardiovascular disease)
研究组 & 干预措施
Lisdexamfetamine - Placebo
干预措施: Placebo (Drug)
Guanfacine - Placebo
干预措施: Placebo (Drug)
Lisdexamfetamine - Guanfacine
干预措施: Guanfacine Extended Release Oral Tablet (Drug)
Guanfacine - Placebo
干预措施: Guanfacine Extended Release Oral Tablet (Drug)
Lisdexamfetamine - Placebo
干预措施: Lisdexamfetamine dimesylate (Drug)
Lisdexamfetamine - Guanfacine
干预措施: Lisdexamfetamine dimesylate (Drug)
结局指标
主要结局
Change in brain activation under the three drug conditions (LISDEX, GXR, placebo)
时间窗: 2 weeks (3 hourly scans one week apart)
Brain activation as measured by blood-oxygen-level-dependent (BOLD) response obtained by fMRI for each of the 3 below listed tasks and functional connectivity measures for the resting state scan. 1. A working memory task (N-back) 2. A tracking stop task 3. A parametric sustained attention task
次要结局
- Changes in dependent variables extracted from performance on the fMRI tasks used under the three drug conditions (LISDEX, GXR, placebo)(2 weeks (3 hourly scans one week apart))
- Changes in dependent variables extracted from performance on a task battery outside the MRI scanner(2 weeks (3 sessions one week apart))