Kbg SyndromePhase 4KBGS_N_of_1NCT06465641
Methylphenidate in KBG Syndrome: N-of-1 Series
A Phase 4 study testing Methylphenidate Hydrochloride in people with Kbg Syndrome and ADHD - Combined Type, run by Radboud University Medical Center at 1 site in Netherlands.
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… Read more about this study
- Who is it for?
- Ages 6 to 20 years
- Conditions the study is for
- Kbg Syndrome, ADHD - Combined Type
- What is being tested?
- Methylphenidate Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteNetherlands
- Study dates
- 13 Nov 2024to 1 Oct 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Radboud University Medical Center
Nijmegen, Gelderland, 6500 HB
Charlotte Ockeloen, MD, charlotte.ockeloen@radboudumc.nl
About this study
Official title: Effectiveness of Methylphenidate in Children and Adolescents With KBG Syndrome: An N-of-1 Series
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.
Read the detailed 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.
- Conditions
- Kbg Syndrome, ADHD - Combined Type
- Being tested
- Methylphenidate Hydrochloride, Placebo
- Medical subject headings
- KBG syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylphenidate HydrochlorideDrug
Methylphenidate hydrochloride in capsules
PlaceboDrug
Microcrystalline cellulose in capsules
| Study group | Role | What they receive |
|---|---|---|
| Methylphenidate | Active comparator | Methylphenidate hydrochloride in capsules Receives: Drug: Methylphenidate Hydrochloride |
| Placebo | Placebo comparator | Microcrystalline cellulose in capsules Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Strenghts and difficulties questionnaire, ADHD subscale
Minimum score 1, maximum score 10 (higher score is worse outcome).
Measured: Baseline, and daily in week 1,3,5,7,9,11
Secondary outcomes (7)
Strenghts and difficulties questionnaire, emotional problems subscale
Minimum score 1, maximum score 10 (higher score is worse outcome).
Measured: Baseline, and daily in week 1,3,5,7,9,11
Dutch shortened version of the Emotion Dysregulation Inventory (EDI) reactivity index
Minimum score 0, maximum score 28 (higher score is worse outcome)
Measured: Baseline, and daily in week 1,3,5,7,9,11
Goal Attainment Scoring (GAS)
Personal goals, no minimum or maximum score
Measured: Baseline, and at the end of week 1,3,5,7,9,11
Personal Questionnaire (PQ)
Personal goals, no minimum or maximum score
Measured: Baseline, and at the end of week 1,3,5,7,9,11
Adverse Effects checklist for methylphenidate
Checklist of adverse effects
Measured: Baseline, and daily in week 1,3,5,7,9,11
McMaster Family assessment device (FAD), subscale General Functioning
10 items, 4 point scale, maximum score 40
Measured: Baseline, and at the end of week 1,3,5,7,9,11
Autism diagnostic observation scale (ADOS-2)
Minimum score 15, maximum score 60 (cut-off score for autism is 30)
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2024
- Study start13 Nov 2024
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kbg SyndromeStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- N-of-1 series (aggregated N-of-1 trial)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06465641
- Sponsor's protocol ID
- 113883
- Acronym
- KBGS_N_of_1
- Status last verified
- Aug 2026
- First submitted
- 6 Feb 2024
- Last updated
- 11 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual patients data that underlie the results after deidentification, study protocol, and statistical analysis plan will be shared upon request following publication, to researchers who provide a methodologically sound proposal.
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of Methylphenidate in Children and Adolescents With KBG Syndrome: An N-of-1 Series
- ClinicalTrials.gov ID
- NCT06465641
- Acronym / sponsor ID
- KBGS_N_of_1 / 113883
- Conditions
- Kbg Syndrome, ADHD - Combined Type
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 13 Nov 2024 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 20 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- N-of-1 series (aggregated N-of-1 trial)
| Arm | Type | Receives |
|---|---|---|
| Methylphenidate | Active comparator | Drug: Methylphenidate HydrochlorideMethylphenidate hydrochloride in capsules |
| Placebo | Placebo comparator | Drug: PlaceboMicrocrystalline cellulose in capsules |
Who may qualify
- Ages
- 6 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylphenidate HydrochlorideMethylphenidate hydrochloride in capsules | Drug | Methylphenidate |
| PlaceboMicrocrystalline cellulose in capsules | Drug | Placebo |
Primary outcome
Strenghts and difficulties questionnaire, ADHD subscale
Time frame: Baseline, and daily in week 1,3,5,7,9,11
Minimum score 1, maximum score 10 (higher score is worse outcome).
7 secondary outcomes
Strenghts and difficulties questionnaire, emotional problems subscale
Time frame: Baseline, and daily in week 1,3,5,7,9,11
Dutch shortened version of the Emotion Dysregulation Inventory (EDI) reactivity index
Time frame: Baseline, and daily in week 1,3,5,7,9,11
Goal Attainment Scoring (GAS)
Time frame: Baseline, and at the end of week 1,3,5,7,9,11
Personal Questionnaire (PQ)
Time frame: Baseline, and at the end of week 1,3,5,7,9,11
Adverse Effects checklist for methylphenidate
Time frame: Baseline, and daily in week 1,3,5,7,9,11
McMaster Family assessment device (FAD), subscale General Functioning
Time frame: Baseline, and at the end of week 1,3,5,7,9,11
Autism diagnostic observation scale (ADOS-2)
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- Individual participant dataSharing planned: Yes. Individual patients data that underlie the results after deidentification, study protocol, and statistical analysis plan will be shared upon request following publication, to researchers who provide a methodologically sound proposal.
Related trials for Kbg Syndrome
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Enrolling by invitation
Palliative Care Needs of Children With Rare Diseases and Their Families
Trisomy 13 Syndrome, Arthrogryposis Congenita Multiplex With Intestinal Atresia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methylphenidate Hydrochloride in people with Kbg Syndrome and ADHD - Combined Type, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Charlotte Ockeloen, MD (+31243613946, charlotte.ockeloen@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Strenghts and difficulties questionnaire, ADHD subscale (time frame: Baseline, and daily in week 1,3,5,7,9,11). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.