Methylphenidate in KBG Syndrome: N-of-1 Series

NCT ID: NCT06465641

Last Updated: 2024-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-13

Study Completion Date

2027-10-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Kbg Syndrome ADHD - Combined Type

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

N-of-1 series (aggregated N-of-1 trial)
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Placebo

Study Groups

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Methylphenidate

Methylphenidate hydrochloride in capsules

Group Type ACTIVE_COMPARATOR

Methylphenidate Hydrochloride

Intervention Type DRUG

Methylphenidate hydrochloride in capsules

Placebo

Microcrystalline cellulose in capsules

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Microcrystalline cellulose in capsules

Interventions

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Methylphenidate Hydrochloride

Methylphenidate hydrochloride in capsules

Intervention Type DRUG

Placebo

Microcrystalline cellulose in capsules

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

6 Years

Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Charlotte Ockeloen, MD

Role: CONTACT

Phone: +31243613946

Email: [email protected]

Facility Contacts

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Charlotte Ockeloen, MD

Role: primary

Other Identifiers

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113883

Identifier Type: -

Identifier Source: org_study_id