Efficacy of Bumetanide to Improve Cognitive Functions in Down Syndrome

Principal inclusion criteria 1. The presence of a free trisomy 21 documented by karyotyping 2. Adolescents from 10 to 17 years old (included) 3. 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 their parents and assent from child/adolescent Principal exclusion criteria 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 i) A 12-lead ECG demonstrating QTc \>450 msec at screening; j) Subject's weight less than 25 Kg. k) Pregnancy as assessed by urine beta HCG