Effectiveness of Methylphenidate in Children and Adolescents With KBG Syndrome: An N-of-1 Series
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Strenghts and difficulties questionnaire, ADHD subscale
研究概览
简要总结
The goal of this clinical trial] is to learn about the effect of methylphenidate in children and adolescents with KBG syndrome. The main question it aims to answer is:
• What is the effectiveness of methylphenidate on attention deficit and ADHD-related symptoms in children and adolescents with KBG syndrome?
Participants will receive multiple blocks of treatment with methylphenidate and placebo and fill out various questionnaires.
详细描述
KBG syndrome (KBGS) is a neurodevelopmental disorder (NDD) characterized by developmental delay and/or intellectual disability, typical facial features, skeletal and congenital anomalies.
Behavioural issues are a frequent feature, reported in 50-94% of persons with KBGS.The behavioural problems are diverse, and include attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), obsessive-compulsive disorder, anxiety, and difficulties in social situations. Van Dongen et al. systematically investigated the behavioural and cognitive phenotype of KBGS patients. This study showed a high level of distractibility, impulsivity and restless behaviour in KBGS patients. As a tertiary reference centre for KBGS in the Netherlands, the investigators notice there is an unmet need for evidence-based interventions for the behavioral problems related to KBGS. A previous survey amongst KBGS caretakers confirmed that (features of) attention-deficit/hyperactivity disorder (ADHD) are the most frequently reported behavioural problems in children with KBGS. Furthermore, the study results indicate that methylphenidate (MPH) has a good effect on ADHD-related symptoms in KBGS, as this is reported by most parents. The promising results from this first exploration on MPH in KBGS indicate that it seems even more effective than in the general population of children with ADHD. However, evidence-based data on optimal dosing and adverse events are lacking. Remarkably, only 2/12 KBGS patients who were treated with stimulants such as MPH had an official ADHD diagnosis. This indicates that patients with ADHD-related symptoms fitting with a probability diagnosis of ADHD, but who do not necessarily fit all the Diagnostic and statistical manual 5 (DSM-5) criteria for ADHD, may also benefit from drug treatment.
The investigators will examine the effectiveness of MPH in children and adolescents with KBGS and (a probability diagnosis of) ADHD, using an N-of-1 series (aggregated N-of-1) trial design.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Placebo
入排标准
- 年龄范围
- 6 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 6-20 years
- •Molecularly confirmed diagnosis of KBG syndrome (pathogenic ANKRD11 variant or a chromosome 16q24 deletion including ANKRD11)
- •Attention deficit or ADHD-related symptoms or a formal ADHD diagnosis, with a significant impact on daily life*
- •Presence of a subject's caregiver or supervisor for proxy-reports
排除标准
- •Family history of acute cardiac death that warrants further cardiac investigation
- •Cardiovascular disease in medical history (severe hypertension, heart failure, arterial occlusive disease, potentially life-threatening arrythmias, angina pectoris, hemodynamically significant congenital heart defect, cardiomyopathy, myocardial infarction and channelopathy)
- •Current or previous presence of hyperthyroidism, glaucoma or pheochromocytoma
- •Use of (psychotropic/stimulant) drugs which interact with MPH
- •Schizophrenic or psychotic disorder in medical history
- •Unstable epilepsy (not controlled with medication)
- •History of frequent drug and/or alcohol abuse
- •Excessive alcohol/drug use and/or intoxication with one or both during the study
- •Pregnant or lactating women
- •Inability to understand or speak Dutch
研究组 & 干预措施
Placebo
Microcrystalline cellulose in capsules
干预措施: Placebo (Drug)
Methylphenidate
Methylphenidate hydrochloride in capsules
干预措施: Methylphenidate Hydrochloride (Drug)
结局指标
主要结局
Strenghts and difficulties questionnaire, ADHD subscale
时间窗: Baseline, and daily in week 1,3,5,7,9,11
Minimum score 1, maximum score 10 (higher score is worse outcome).
次要结局
- Strenghts and difficulties questionnaire, emotional problems subscale(Baseline, and daily in week 1,3,5,7,9,11)
- Dutch shortened version of the Emotion Dysregulation Inventory (EDI) reactivity index(Baseline, and daily in week 1,3,5,7,9,11)
- Personal Questionnaire (PQ)(Baseline, and at the end of week 1,3,5,7,9,11)
- Goal Attainment Scoring (GAS)(Baseline, and at the end of week 1,3,5,7,9,11)
- Adverse Effects checklist for methylphenidate(Baseline, and daily in week 1,3,5,7,9,11)
- McMaster Family assessment device (FAD), subscale General Functioning(Baseline, and at the end of week 1,3,5,7,9,11)
- Autism diagnostic observation scale (ADOS-2)(Baseline)