Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Authorised, recruiting
Participants planned
280
Countries
2
Sites
12
Autism spectrum disorder
Our goal is to study the effectivity of therapeutic drug monitoring to prevent or mitigate side-effects of risperidone and aripiprazole use in children and adolescents. To this end we will study the differences in weight gain six months after start of treatment with risperidone or aripiprazole between a group of child…
Key facts
- Sponsor
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Psychiatry and Psychology [F] - Mental Disorders [F03]
- Trial duration
- 16 Jul 2024 → ongoing
- Decision date (initial)
- 2024-07-31
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- ZonMw · Stichting de Merel · Erasmus MC
External identifiers
- EU CT number
- 2024-511568-96-00
- EudraCT number
- 2020-005450-18
- ClinicalTrials.gov
- NCT05146245
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety, Pharmacodynamic, Pharmacokinetic
Our goal is to study the effectivity of therapeutic drug monitoring to prevent or mitigate side-effects of risperidone and aripiprazole use in children and adolescents.
To this end we will study the differences in weight gain six months after start of treatment with risperidone or aripiprazole between a group of children receiving therapeutic drug monitoring based dosing advice and a group of children receiving risperidone or aripiprazole according to standard clinical care.
Secondary objectives 3
- To study the differences in weight gain one year after start of treatment
- To compare the drug effectivity between the groups, based on severity of irritability and aggression as measured by the Aberrant Behavior Checklist (ABC).
- To compare the following safety parameters between the groups: levels of glucose, cholesterol, lipoproteins and triglycerides; the hormones ghrelin, prolactin and leptin as well the level of extrapyramidal side effects as measured by the Abnormal Involuntary Movement Scale (AIMS), and quality of life, measured using the Pediatric Quality of Life Inventory (PedsQL), EuroQol-5D-Y (EQ-5D-Y), and Treatment Inventory of Costs in Patients with psychiatric disorders (TIC-P).
Conditions and MedDRA coding
Autism spectrum disorder
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | TDM or CAU Patients will be randomised to receive therapeutic drug monitoring or care as usual (CAU), which does not include therapeutic drug monitoring
|
Randomised Controlled | None | Therapeutic drug monitoring: In the TDM arm, trough drug plasma levels will be measured by means of DBS 4 and 10 weeks after start of antipsychotic treatment, in steady state. A tailored advice for dose adjustment will be given to the psychiatrist guided by a standardized, laboratory hospital pharmacist managed, PK/PD-model based dosing program (InsightRX®). Care As Usual: In the CAU arm no dosing recommendations will be given. |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2020-005450-18 | SPACe 2 STAR : Safety and pharmacokinetics of antipsychotics in children 2. Studying TDM in An RCT |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- Age 6 to 18 years Documented clinical diagnosis of autism spectrum disorder according to DSM IV or DSM V and comorbid behavioural problems To start treatment with risperidone or aripiprazole
Exclusion criteria 1
- Diabetes type I or II Congenital or acquired syndrome associated with changes in appetite, body weight or lipid profile (e.g. Prader Willi) Known history of Long QT syndrome (LQTS), cardiovascular disorders (myocardial infarction or ischaemic heart disease, heart failure, or conduction abnormalities), seizure disorder or oesophageal dysmotility Pregnancy Hypersensitivity to the active substance or to any of the excipients
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Difference between the groups in change in body mass index z-scores (BMI-Z) after 6 months of treatment
Secondary endpoints 9
- Difference between the groups in change in body mass index z-scores (BMI-Z) after 12 months of treatment.
- Aberrant Behavior Checklist, a parental symptom checklist for assessing problem behaviour in children. The gold standard for measuring the effect of treatment on aggression and irritability in children with autism spectrum disorder
- EuroQol-5D Youth. A descriptive system for health-related quality of life states in five dimensions, plus a visual analogue scale.
- Pediatric Quality of Life Inventory. A modular instrument aimed at measuring healthrelated quality of life in children and adolescents. It showed excellent reliability and validity in individuals with autism spectrum disorder
- Clinical Global Improvement
- Treatment Inventory of Costs in Patients with psychiatric disorders. A modular questionnaire aimed at mapping healthcare utilization and the repercussions of psychosocial problems, allowing for the assessment of associated costs.
- Levels of glucose, cholesterol, lipoproteins and triglycerides; the hormones ghrelin, prolactin and leptin.
- Abnormal Involuntary Movement Scale, a clinician administered observational scale aimed at detecting extrapyramidal side effects.
- Blood pressure
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
SCP106382107 · ATC
- Active substance
- Aripiprazole
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- N05AX12 — ARIPIPRAZOLE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1020186 · ATC
- Active substance
- Risperidone
- Substance synonyms
- 3-[2-[4-(6-FLUORO-1,2-BENZOXAZOL-3-YL)PIPERIDIN-1-YL]ETHYL]-2-METHYL-6,7,8,9-TETRAHYDROPYRIDO[2,1-B]PYRIMIDIN-4-ONE
- Route of administration
- ORAL
- Max daily dose
- 0.08 mg/kg milligram(s)/kilogram
- Max total dose
- 0.08 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- N05AX08 — RISPERIDONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Sponsor organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Address
- Dr. Molewaterplein 40
- City
- Rotterdam
- Postcode
- 3015 GD
- Country
- Netherlands
Scientific contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- Dr. B. Dierckx
Public contact point
- Organisation
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Contact name
- Dr. B. Dierckx
Locations
2 EU/EEA countries · 12 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ended | 30 | 2 |
| Netherlands | Ongoing, recruiting | 250 | 10 |
| Rest of world | — | 0 | — |
Investigational sites
Tübingen University Hospital
Kinder- und Jugendpsychiatrie, Hoppe-Seyler-Straße 3, Germany, Tübingen
Wurzburg University Hospital
Kinder- und Jugendpsychiatrie, Josef-Schneider-Strasse 2, Grombuehl, Wuerzburg
KJP Mariaberg
Kinder- und Jugendpsychiatrie, Burghaldenstraße 12, 72501, Gammertingen
Karakter
KJPP, Horalaan 5, Netherlands
Yulius GGZ
KJPP, Burgemeester de Raadtsingel 93c, Netherlands
Erasmus MC
KJPP, Erasmus MC, Netherlands
GGz Breburg
KJPP, Jan Wierhof 7, Netherlands
GGZ Delfland
KJPP, Sint Jorisweg 2, Netherlands
Accare
KJPP, Groningerstraat 352, Netherlands
's Heeren Loo
KJPP, Berkenweg 11, Netherlands
Mondriaan
KJPP, Vijverdalseweg 1, Netherlands
LUMC Curium
KJPP, Endegeesterstraatweg 27, Netherlands
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2024-07-16 | 2024-07-16 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 13 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Protocol 2020-005450-18 redacted | 6 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangement | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangement | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 12-15 years | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 12-15 years | 7 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 16-18 years | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 16-18 years | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 6-11 years | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 6-11 years | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF parents | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF parents | 8 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Aripiprazole | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Risperidone | 2 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-20 | Netherlands | Acceptable with conditions 2024-07-16
|
2024-07-16 |