Attention Management Trial for Children With FASD - a N-of-1 Control Trial of Prescribed Stimulants for ADHD in FASD
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in ADHD symptoms - teacher report - between placebo and stimulant
研究概览
简要总结
This study is a double-blind, placebo controlled, series of N-of-1 trials of individualised stimulant dose on ADHD symptomatology in children with FASD.
The broad aim of this study is to contribute new evidence towards understanding treatment efficacy for ADHD symptoms in FASD.
Specific aims are:
- To assess the ongoing effectiveness of stimulant medication prescribed for ADHD symptoms in individual children with FASD of clinically prescribed stimulant medication compared to placebo to control ADHD symptoms (using behavioural and cognitive measures) in children with FASD and ADHD using a N-of-1 trial design.
- To obtain pilot data to examine feasibility and tolerability of the planned N-of-1 trial design in children with FASD and ADHD for future and larger studies that might seek to examine if the different stimulant types are equally effective relative to placebo.
- To review the multiple N-of-1 data to analyze key individual factors that mediate the effect of stimulants relative to placebo on ADHD symptoms, including underlying child factors (attention skills, cognitive function), sociodemographic factors and other prenatal exposures.
详细描述
Study Design:
This is a single site, double-blind, placebo controlled, N-of-1 trial of clinically prescribed, individualised stimulant dose on ADHD symptomatology in children with FASD. The N-of-1 trial has four 2-week treatment blocks (each block consisting of 1 week active drug and 1 week placebo). Interventions will include either prescribed stimulant (active drug) or matched placebo capsules, compared in four 2-week treatment blocks (each block consisting of 1 week active drug and 1 week placebo). Participants will be randomized to the sequence of the treatment arms. Randomisation will be in the two-week pairs - so the order of treatment (A) and placebo (P) to be randomly assigned within each two-week cycle.
Secondarily the investigators will collate outcomes across the N-of-1 trials and make use of a 'series' or multiple N-of-1 trial design18, chosen as it is a valid method of trial design for rare clinical disorders where individualized treatments are required. This design can result in robust evidence, assuming standards of methodological practice.1 In an N-of-1 trial, each participant is assured of receiving both the study medication and placebo, and thus learns whether the treatment works specifically for them or not.
Study objectives:
- Primary objective:
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)
盲法说明
The order of medications (placebo/active drug) will be masked to the participant, assessors and investigator. At the end of the trial, the order of medications will be unmasked, and compared with the parent and teachers' observations of the child's behaviour.
入排标准
- 年龄范围
- 4 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Each patient must meet all of the following criteria to be enrolled in this trial:
- •Is between the ages of 4 - 18 years at the time of randomization.
- •Meet diagnostic criteria for FASD or at risk of FASD according to the Australian Guide to the diagnosis of FASD.
- •Is a patient of VicFAS or Developmental Paediatrics (Monash Health).
- •Has a diagnosis of ADHD according to the DMS-IV criteria.
- •Be on a stimulant medication for treatment of ADHD symptoms.
- •Be on a stimulant medication as a primary treatment for ADHD.
- •Be on a stable dose of stimulant medication for at last 1 month prior to the study.
- •Provide a signed and dated informed consent form / and has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf.
- •If seen by VicFAS/Developmental paediatrics between August 2019 - study commencement date), parent/guardian must have provided verbal or written consent to the VicFAS database PICF and selected 'yes' to the optional consent for contact for 'future research'.
排除标准
- •Exclusion criteria will include any of the following:
- •Inability to read or speak sufficient English for either child or parent/guardian to complete assessment tasks.
- •Be on a medication for treatment of ADHD symptoms that is a medication other than stimulants as a primary treatment for ADHD.
- •Allergy/sensitivity to Starcke 1500 (Maize Starch and Pregelatinised Maize Starch).
- •Unable to swallow capsules.
- •Intracranial symptoms or pathology such as epilepsy, hydrocephalus, diagnosed traumatic. brain injury or progressive intracranial tumours that may impact cognitive and behavioural function (children with asymptomatic or static lesions will be eligible).
- •An abnormal ECG result at the time of screening deemed clinically significant by study physician.
- •Presence of a significant comorbid psychiatric or psychological (excluding ADHD, oppositional defiant disorder, conduct disorder and pervasive development disorder/autism spectrum disorder) including depressive disorder, anxiety disorder, psychotic disorder, suicidality, Tic disorder, anorexia or bulimia nervosa
- •Has a known hypersensitivity to starch or other compound relevant to placebo/capsules.
- •Has had treatment with any other investigational drug within 4 weeks prior to randomisation.
- •If the participant is known to be pregnant, they cannot take part in this research project.
- •Parent/guardian not consenting to contact with paediatrician or school.
- •Is deemed by their treating paediatrician to be medically unsafe for trial participation.
- •Child's school unwilling to participate in outcome assessments.
研究组 & 干预措施
Placebo comparator 2
Participants will be allocated a randomly allocated sequence of treatment. The randomisation will be in two-week pairs - so the order of treatment (A) and placebo (P) to be randomly assigned within each two-week cycle (over 8 weeks). Placebo will be matched in dose to their stimulant dose at enrolment to the trial as determined and titrated by their primary paediatrician. This dose will remain constant for the course of the trial (8 weeks). Placebo will be orally administered, unless this is not possible for clinical reasons.
干预措施: Placebo (Drug)
Stimulant
The stimulants used in the trial are commercially available and will be used in accordance with the approved labelling. Participants must be on a stable dose of stimulant medication for at last 1 month prior to the study. The dose is individualized and titrated by treating primary paediatrician. This will represent the starting dose for the trial, and this will remain stable through the course of the 8-week trial. This study is a N-of-1 RCT of currently prescribed stimulant medications for treatment of ADHD symptoms in children with FASD, relative to matched placebo capsules. Based on pilot data from this group, psychostimulant medications prescribed in this population may include:
- Methylphenidate IR
- Methylphenidate LA
- Dexamphetamine
Children will take the required number of capsules to match the total prescribed dose (e.g. 30mg Ritalin LA is 3x10mg capsules).
干预措施: Methylphenidate hydrochloride (Drug)
Stimulant
The stimulants used in the trial are commercially available and will be used in accordance with the approved labelling. Participants must be on a stable dose of stimulant medication for at last 1 month prior to the study. The dose is individualized and titrated by treating primary paediatrician. This will represent the starting dose for the trial, and this will remain stable through the course of the 8-week trial. This study is a N-of-1 RCT of currently prescribed stimulant medications for treatment of ADHD symptoms in children with FASD, relative to matched placebo capsules. Based on pilot data from this group, psychostimulant medications prescribed in this population may include:
- Methylphenidate IR
- Methylphenidate LA
- Dexamphetamine
Children will take the required number of capsules to match the total prescribed dose (e.g. 30mg Ritalin LA is 3x10mg capsules).
干预措施: Methylphenidate Hydrochloride 18 MG (Drug)
Stimulant
The stimulants used in the trial are commercially available and will be used in accordance with the approved labelling. Participants must be on a stable dose of stimulant medication for at last 1 month prior to the study. The dose is individualized and titrated by treating primary paediatrician. This will represent the starting dose for the trial, and this will remain stable through the course of the 8-week trial. This study is a N-of-1 RCT of currently prescribed stimulant medications for treatment of ADHD symptoms in children with FASD, relative to matched placebo capsules. Based on pilot data from this group, psychostimulant medications prescribed in this population may include:
- Methylphenidate IR
- Methylphenidate LA
- Dexamphetamine
Children will take the required number of capsules to match the total prescribed dose (e.g. 30mg Ritalin LA is 3x10mg capsules).
干预措施: Dexamphetamine sulfate (Drug)
结局指标
主要结局
Change in ADHD symptoms - teacher report - between placebo and stimulant
时间窗: Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)
ADHD symptoms will be measured using the Conners 3rd Edition-Teacher (Conners 3-T), for 6-18 year old's and the Conners Early Childhood teachers/childcare providers (full length) form for participants 2-6 years. Each item is rated on a Likert scale from 0 to 3 (0=never or rarely; 1=sometimes; 2=often; 3=very often). Test- retest values for the Conners scales indicate excellent temporal stability (ranging from .73 to 1.00). The T-score is norm referenced, with a mean of 50. The average range falls within one standard deviation of the mean (i.e., between 40 and 59). A higher score indicates more elevated symptoms. T score Guideline 70+Very Elevated Score 65-69 Elevated Score 40-59 Average score 60-64 High average score \< 40 Low score. Investigators will examine Inattentive and Hyperactivity/Impulsivity Symptom Scales. Symptoms indicated for each subscale are summed to get total.
Change in ADHD symptoms - parent report - between placebo and stimulant
时间窗: Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total)
ADHD symptoms will be measured using the Conners 3rd Edition-Parent (Conners 3-P), for 6-18 year old's and the Conners Early Childhood parent (full length) form for participants 2-6 years. Each item is rated on a Likert scale from 0 to 3 (0=never or rarely; 1=sometimes; 2=often; 3=very often). Test- retest values for the Conners scales indicate excellent temporal stability (ranging from .73 to 1.00). The T-score is norm referenced. The average range falls within one standard deviation of the mean (i.e., between 40 and 59). A higher score indicates more elevated symptoms. T score Guideline 70+Very Elevated Score 65-69 Elevated Score 40-59 Average score 60-64 High average score \< 40 Low score. Investigators will examine Inattentive and Hyperactivity/Impulsivity Symptom Scales. Symptoms indicated for each subscale are summed to get the total.
Change in spatial working memory - between placebo and stimulant
时间窗: Day 3 of each trial week (8 weeks total)
Spatial Working Memory (SWM) task from the Cambridge Neuropsychological Test Automated Battery. SWM is a component of cognitive executive function which is measured by SWM task of CANTAB between the errors. The ability to retain spatial information and manipulate remembered items in working memory will be measured with the SWM task of CANTAB which is self-ordered and assesses the individual's ability to strategise. Between search errors will be analysed. Scores are raw scores, with no normative data available. Higher error score indicated poorer performance. Scale does not have a maximum range.
Change in Visual Information Processing - between placebo and stimulant
时间窗: Day 3 of each trial week (8 weeks total)
Rapid Visual Information Processing (SOC) from Cantab. SOC Stockings of Cambridge (SOC) is a test of spatial planning that requires individuals to use problem-solving strategies to match two sets of stimuli. The participant must move the balls in the bottom display to copy the pattern shown in the top display. The balls are moved one at a time by selecting the required ball, then selecting the position to which it should be moved. The participant is instructed to make as few moves as possible to match the two pattern. The outcome measure of this subtest is the number of problems completed, regardless of whether the maximum moves limit was reached on any problem.
次要结局
- Assessment completion rate(End of 8 month active trial phase)
- Change in child problem behaviour rating- between placebo and stimulant(Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total))
- Change in functional Impairment- between placebo and stimulant(Daily for 5 week days (Monday - Friday) of each trial week (8 weeks total))
- Difference in side effects during placebo and stimulant phase(Day 5 of each trial week (8 weeks total))
- Trial feasibility - recruitment rate(End of 8 month active trial phase)
- Trial feasibility - completion rate(End of 8 month active trial phase)
- Compliance(End of 8 month active trial phase)
- Data completion reason(End of 8 month active trial phase)
- Adverse events(End of 8 month active trial phase)
研究者
Alison Crichton
Principal Investigator
Monash Medical Centre