Bumetanide for Down syndrome

Inclusion criteria

• {"criterion_text":"- 1) The presence of a free trisomy 21 documented by karyotyping\n- 2) Adolescents from 10 to 17 years old (included)\n- 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)\n- 4) Informed consent from each child and their parents."}

Exclusion criteria

• {"criterion_text":"- 1) The presence of any neurosensory deficits, such as hypoacusis or serious visual impairments\n- 2) The presence of epilepsy\n- 3) The presence of electrolyte disorders\n- 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.\n- 5) The presence of a hypersensibility known about sulpha drugs\n- 6) The presence of contraindications relative to the treatment by bumetanide\n- 7) Patients already treated by diuretics\n- 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\n- 9) A 12-lead ECG demonstrating QTc >450 msec at Screening\n- 10) Subject’s weight less than 25 Kg\n- 11) Pregnancy as assessed by urine beta HCG"}

Primary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Measured by the Visual-Object learning test; primary endpoint defined as a 22% increase in the mean total score after three months of treatment (comparison of mean total scores pre- and post-treatment; threshold based on test-retest reliability and healthy population improvement)."}

Secondary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Comparative improvement at 3 months between bumetanide and placebo in: total and subdomain scores of episodic memory tasks (verbal, visual-spatial, associative memory); BRIEF2 parent-report executive function measures; psychopathological measures; adaptive level; and quality of life instruments (scores compared between groups at baseline and after 3 months)."}

Methods

• K1_Recruitment arrangement document (recruitment plan) — materials and arrangement documented for recruitment (country: Italy).
• L_LOCANDINA social — social poster for social media recruitment targeting parents/caregivers of children and adolescents with Down syndrome.
• L_Brochure informativa cartacea / L_Brochure informativa relativa allo studio — printed informational brochures for families and clinics.
• L_Presentazione ppt — presentation materials (for information sessions to families/clinics).

Italy

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

09-01-2026

Processing Time Days

435

Number Of Sites

1

Number Of Participants

64

Primary sponsor

Full Name

Ospedale Pediatrico Bambino Gesu

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy