Pharmacological and non-pharmacological interventions in Down syndrome: a ClinicalTrials.gov-based analysis of completed studies with results

Background Down syndrome (DS) is a genetic condition associated with intellectual disability, cognitive impairment, and multiple comorbidities. Despite advances in supportive care, effective therapeutic interventions targeting cognitive and functional outcomes remain limited. This study aimed to analyze completed clinical trials with available results registered on ClinicalTrials.gov that investigate interventions for individuals with Down syndrome. Methods A retrospective registry-based analysis was conducted using ClinicalTrials.gov. Studies were included if they (1) involved Down syndrome, (2) were completed, and (3) reported results. Data extracted included study design, intervention type, enrollment size, and primary outcomes. Descriptive analysis was performed. Results A total of 34 studies met the inclusion criteria. The majority were interventional ( n = 33, 97%), with only one observational study (3%). Most trials were randomized controlled trials. Interventions included pharmacological therapies such as cognitive enhancers, behavioral interventions, nutritional supplementation, and supportive therapies. Enrollment sizes were generally small, with 23 studies (≈68%) enrolling fewer than 50 participants. Primary outcomes commonly focused on cognitive function, behavioral improvement, and safety. Conclusion Clinical trials in Down syndrome predominantly focus on interventional strategies targeting cognitive and functional outcomes. However, small sample sizes and heterogeneity in outcome measures limit generalizability. Greater standardization and larger-scale studies are needed to improve translational impact.