Overview
Sponsor-declared trial summary
Down Syndrome
The aim of the study is to investigate the potential of 3 months of treatment with Bumetanide to rescue cognitive functions and associated psychopathological aspects in DS of Bumetanide treatment in children and adolescents with DS aged 10-16 years. The overreaching goal of our project is to test the ability of a treat…
Key facts
- Sponsor
- Ospedale Pediatrico Bambino Gesu
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Trial duration
- 11 Jan 2023 → ongoing
- Decision date (initial)
- 2025-02-03
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Jerome Lejeune Foundation - Stati Uniti
External identifiers
- EU CT number
- 2024-519342-71-00
- EudraCT number
- 2015-005780-16
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Safety, Efficacy
The aim of the study is to investigate the potential of 3 months of treatment with Bumetanide to rescue cognitive functions and associated psychopathological aspects in DS of Bumetanide treatment in children and adolescents with DS aged 10-16 years. The overreaching goal of our project is to test the ability of a treatment with Bumetanide to rescue cognitive functions and associated psychopathological aspects in children and adolescents with DS. As Bumetanide has been extensively used in the past in humans with little side effects, it is orally active, and it is very economical, we will test here the potentials of our therapeutic approach to be translated directly in a clinical trial on a cohort of DS patients.
Conditions and MedDRA coding
Down Syndrome
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- 1) The presence of a free trisomy 21 documented by karyotyping 2) Adolescents from 10 to 17 years old (included) 3) 4.5 ≥ Mental age ≤ 8.5 (as assessed by Leiter-3 at visit 1 or by assessment with Leiter-3 within 6 months of the first visit (Visit 1) 4) Informed consent from each child and their parents.
Exclusion criteria 1
- 1) The presence of any neurosensory deficits, such as hypoacusis or serious visual impairments 2) The presence of epilepsy 3) The presence of electrolyte disorders 4) The presence of clinically and/or hemodynamically significant congenital heart defects, defined as patients with congenital heart disease who already underwent or are awaiting surgical/percutaneous correction (including palliative cardiac surgery as Glenn and/or Fontan) or who are under current treatment with cardiac medications. 5) The presence of a hypersensibility known about sulpha drugs 6) The presence of contraindications relative to the treatment by bumetanide 7) Patients already treated by diuretics 8) Any of the following abnormal laboratory values at screening: - Hemoglobin <10 g/dL - Abnormal liver function defined as any 2 or more of the following: ≥3 × upper limit of normal (ULN) aspartate aminotransferase (AST), ≥3 × ULN alanine aminotransferase (ALT), ≥3 × ULN gamma-glutamyl transpeptidase (GGT), ≥3 × ULN alkaline phosphatase (ALP), or ≥2 × ULN total bilirubin - Abnormal liver function defined as any increase of ≥5 × ULN AST or ALT - Estimated glomerular filtration rate ≤80 mL/min/1.73 m2 (calculated by the Schwartz equation) - Plasma HCO3 > 32 9) A 12-lead ECG demonstrating QTc >450 msec at Screening 10) Subject’s weight less than 25 Kg 11) Pregnancy as assessed by urine beta HCG
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary end-point will be the improvement at the Visual-Object learning test, defined as the increase of 22% in the mean total score occurred after three months of treatment. This improvement is considered clinically significant since the value is similar to the improvement in the healthy population (22,6%), considering the test-retest reliability at three months (Vicari et al., 2007).
Secondary endpoints 1
- Secondary end-points will be significant higher improvement in the bumetanide group compared to the placebo group after 3 months in the total scores and subdomain scores of the other episodic memory tasks (Verbal and Visual-Spatial long-term memory, associative memory); the executive function measures (Behavior Rating Inventory Executive Function Second Edition questionnaire – parent report form - BRIEF2), the psychopathological measures, the adaptive level and quality of life
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD7212288 · Product
- Active substance
- Bumetanide
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 4 mg milligram(s)
- Max total dose
- 360 mg milligram(s)
- Max treatment duration
- 3 Month(s)
- Authorisation status
- Authorised
- ATC code
- C03CA02 — BUMETANIDE
- Marketing authorisation
- 9001
- MA holder
- KARO PHARMA AB
- MA country
- Sweden
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Ospedale Pediatrico Bambino Gesu
- Sponsor organisation
- Ospedale Pediatrico Bambino Gesu
- Address
- Piazza Di Sant'onofrio 4
- City
- Rome
- Postcode
- 00165
- Country
- Italy
Scientific contact point
- Organisation
- Ospedale Pediatrico Bambino Gesu
- Contact name
- Stefano Vicari
Public contact point
- Organisation
- Ospedale Pediatrico Bambino Gesu
- Contact name
- Stefano Vicari
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruiting | 64 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
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 |
|---|---|---|---|---|---|
| Italy | 2023-01-11 | 2023-01-11 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 16 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Bumetanide_CRF_forpublication | 0.6 |
| Protocol (for publication) | D_Bumetanide_Protocollo_forpublication | 8 |
| Protocol (for publication) | D_Bumetanide_Protocollo_fP | 8.1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangement | 1 |
| Subject information and informed consent form (for publication) | L_Brochure informativa cartacea | 1 |
| Subject information and informed consent form (for publication) | L_Brochure informativa relativa allo studio_notforpublication | 1 |
| Subject information and informed consent form (for publication) | L_Consenso e Informativa Biobanca Gaslini | Ed.5 |
| Subject information and informed consent form (for publication) | L_ICF_genitori del minore_studi clinici_notforpublication | 5 |
| Subject information and informed consent form (for publication) | L_ICF_privacy_genitori_tutore_legale_notforpublication | 4 |
| Subject information and informed consent form (for publication) | L_LOCANDINA social | 1.1 |
| Subject information and informed consent form (for publication) | L_Presentazione ppt | 1 |
| Subject information and informed consent form (for publication) | L_Scheda informativa e assenso Adolescenti_notforpublication | 2 |
| Subject information and informed consent form (for publication) | L_Scheda informativa e dichiarazione di assenso Bambini_notforpublication | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G_SmPC-202005-Burinex 1 mg-ie | 1 |
| Synopsis of the protocol (for publication) | D_Bumetanide_Sinossi del protocollo_forpublication | 4 |
| Synopsis of the protocol (for publication) | D_Bumetanide_Sinossi del protocollo_fP | 4.1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-12-23 | Italy | Acceptable 2025-01-21
|
2025-02-03 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-01-09 | Italy | Acceptable 2025-01-21
|
2026-01-09 |