Methylphenidate in KBG Syndrome: N-of-1 Series

ADHD - Combined Type Clinical Trial

— KBGS_N_of_1  

Official title:

Effectiveness of Methylphenidate in Children and Adolescents With KBG Syndrome: An N-of-1 Series

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06465641
• Other study ID #: 113883
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: September 1, 2024
• Est. completion date: October 1, 2027

Study information

• Verified date: February 2024
• Source: Radboud University Medical Center
• Contact: Charlotte Ockeloen, MD
• Phone: +31243613946
• Email: charlotte.ockeloen[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 15
• Est. completion date: October 1, 2027
• Est. primary completion date: January 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 20 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Abnormalities, Multiple
• ADHD - Combined Type
• Bone Diseases, Developmental
• Facies
• Intellectual Disability
• Syndrome
• Tooth Abnormalities

Intervention

Drug:
• Methylphenidate Hydrochloride
Methylphenidate hydrochloride in capsules
• Placebo
Microcrystalline cellulose in capsules

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University Medical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Strenghts and difficulties questionnaire, ADHD subscale	Minimum score 1, maximum score 10 (higher score is worse outcome).	Baseline, and daily in week 1,3,5,7,9,11
Secondary	Strenghts and difficulties questionnaire, emotional problems subscale	Minimum score 1, maximum score 10 (higher score is worse outcome).	Baseline, and daily in week 1,3,5,7,9,11
Secondary	Dutch shortened version of the Emotion Dysregulation Inventory (EDI) reactivity index	Minimum score 0, maximum score 28 (higher score is worse outcome)	Baseline, and daily in week 1,3,5,7,9,11
Secondary	Goal Attainment Scoring (GAS)	Personal goals, no minimum or maximum score	Baseline, and at the end of week 1,3,5,7,9,11
Secondary	Personal Questionnaire (PQ)	Personal goals, no minimum or maximum score	Baseline, and at the end of week 1,3,5,7,9,11
Secondary	Adverse Effects checklist for methylphenidate	Checklist of adverse effects	Baseline, and daily in week 1,3,5,7,9,11
Secondary	McMaster Family assessment device (FAD), subscale General Functioning	10 items, 4 point scale, maximum score 40	Baseline, and at the end of week 1,3,5,7,9,11
Secondary	Autism diagnostic observation scale (ADOS-2)	Minimum score 15, maximum score 60 (cut-off score for autism is 30)	Baseline