Using Bumetanide to Enhance Memory in Children with Down Syndrome

A Phase 2 Double Blind Placebo Controlled Study on the Efficacy of Bumetanide for Cognitive Improvement in Children and Adolescents With Down Syndrome

This study is testing if a medication called Bumetanide can help improve memory and thinking skills in children and teens with Down syndrome.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 64 (estimated)
• Ages: 10 Years to 17 Years
• Sex: All
• Sponsor: Bambino Gesù Hospital and Research Institute (Academic / other)
• Locations: 1 site (Rome)
• Trial ID: NCT06465823 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of Bumetanide, a diuretic, in improving memory and cognitive functions in children and adolescents with Down syndrome. It aims to identify biological and genetic markers that may predict treatment efficacy. The study builds on previous animal research indicating that Bumetanide can restore synaptic balance and improve learning abilities. Participants will receive either Bumetanide or a placebo to assess the drug's impact on cognitive performance.

Who should consider this trial

Good fit: Ideal candidates are adolescents aged 10 to 17 with a confirmed diagnosis of Down syndrome and specific cognitive assessment scores.

Not a fit: Patients with significant neurosensory deficits, epilepsy, or serious congenital heart defects may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly enhance cognitive functions and quality of life for children with Down syndrome.

How similar studies have performed: Preliminary studies have shown promise in using Bumetanide for cognitive enhancement in similar neurodevelopmental disorders, suggesting potential for success in this approach.

Eligibility criteria

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

Where this trial is running

Rome

• Bambino Gesù Children's Hospital — Rome, Italy (Recruiting)

Study contacts

• Principal investigator: Stefano Vicari — Bambino Gesù Children's Hospital
• Study coordinator: Paolo Alfieri

Conditions Down Syndrome; Bumetanide, GABA, NKCC1, Memory