ABSTRACT Carpal tunnel syndrome is a commonly diagnosed hand disorder that is routinely treated by surgicallytransecting the transverse carpal ligament to reduce pressure on the median nerve and to alleviate symptoms.Despite known complications of surgery including reduced hand function and symptom recurrence thesurgical technique has remained fundamentally unchanged since the early twentieth century. Non-surgicalinterventions where the wrist is therapeutically manipulated have been developed but these modalities havenot gained widespread acceptance due to a lack of scientific and clinical evidence of efficacy. Our previousinvestigations have identified a novel mechanism for median nerve decompression the core concept of whichis that radioulnar wrist compression leads to carpal arch space augmentation (CASA) and subsequently tomedian nerve decompression. In contrast to currently available therapeutic methods which aim to increase thewidth of the carpal arch our approach narrows the arch width in order to increase the arch height and cross-sectional area. This novel biomechanical intervention is supported by our extensive research including in vitrocadaveric experiments geometric modeling finite element analysis in vivo human experimentation andpreclinical feasibility studies. Building upon these scientific and clinical premises we plan to carry out a singlesite double-blinded randomized controlled clinical trial pilot study to demonstrate the treatment efficacy ofCASA for carpal tunnel syndrome and compare the therapeutic effects with a sham device. The SpecificAims of the project are (1) to demonstrate that non-surgical CASA intervention improves symptoms and handfunction in patients with carpal tunnel syndrome; (2) to compare the clinical outcomes of CASA interventionwith a sham intervention; and (3) to demonstrate the feasibility and scalability of a multisite randomizedcontrolled full-scale clinical trial comparing CASA intervention and sham intervention. We hypothesize that (i)four-weeks of CASA intervention will alleviate carpal tunnel syndrome symptoms and improve hand functionand that the beneficial effects will persist beyond the intervention period; (ii) CASA intervention will result ingreater improvement of symptoms and function than the sham intervention; and (iii) recruitment will be feasibleretention rates and compliance will be acceptable and the treatment will be safe. Results of this pilot clinicaltrial will allow us to understand the expected treatment effects of CASA intervention refine sample size setexpectations for patient compliance and dropout rates and inform the design of a larger scale multisiterandomized controlled clinical trial of CASA intervention. This pilot trial is a crucial step in our preparation toeffectively launch a full-scale multisite clinical trial eventually translating our scientifically meritoriousbiomechanical principle of CASA and research findings into a novel non-surgical treatment of carpal tunnelsyndrome.