A 12 Week Double Blind Placebo Clinical Trial to Evaluate the Safety and Efficacy of Rivastigimine in Children with Down Syndrome

Principal Investigator: George Capone

Individuals with Down syndrome (DS) exhibit a notable cholinergic deficiency by the 4th decade of life. It is unclear how early in life presynaptic cholinergic deterioration begins or how it evolves in subsequent decades. Acetylcholinesterase inhibitors (AchEIs) may improve cognitive and language function in adult individuals and adolescents with DS. As demonstrated in a recent open-label study, investigators reported on the short-term safety and efficacy using a liquid formulation of Rivastigmine (Excelon TM), an acetyl and butyryl cholinesterase inhibitor, in eleven subjects with DS ages 10-17 years. Four subjects experienced no adverse events (AE), and seven subjects reported AEs that were mild, transient and consistent with known AEs common to AchEIs. Significant improvements were found in measures of Adaptive function (Vineland scales), attention (Leiter Attention tests), memory (NEPSY Narrative and Immediate Memory subtest), and language (TOVER and CELF) domains. We hypothesize that these apparent improvements, from the open-label study, are in fact due to an effect of medication. The need to perform this study using a larger sample size and randomized clinical trial (RCT) design seem obvious. The results of such a study would contribute to the body of evidence suggesting a role for AchEIs in the management of cognitive and language dysfunction in children & adolescents with DS. We are now studying subjects for a longer treatment duration of 20 weeks in order to fully assess the efficacy of Rivastgimine.