Mechanism of Action of Vibrant Capsule for the Treatment of Chronic Idiopathic Constipation: Pooled Results of 2 Different Studies

Abstract

Introduction: Chronic constipation is a multifactorial gastrointestinal (GI) disorder. Although several treatments are available, many patients remain dissatisfied and desire new therapies. The orally administered intraluminal vibrating capsule (VC) (Vibrant Ltd., Yokneam, Israel) is the first chemical-free treatment that improves constipation by mechanically inducing vibrations. Our aim was to determine the effects of VC on complete spontaneous bowel movements (CSBMs) in patients with chronic idiopathic constipation (CIC), using 2 paradigms of VC activation. Methods: Patients with CIC who fulfilled Rome III criteria were enrolled in 2 double-blind, sham-controlled studies. Subjects ingested 5 capsules per week for 8 weeks. Patients in study 1 (n=182) received a single vibration session, and in study 2 (n=63) multiple (3) vibration sessions/day using similar frequency in both studies. Bowel symptoms were recorded on daily stool diary. Results: Data on CSBM frequency from the 2 studies were pooled for this analysis. A significant correlation was found with single vibration (study 1) between the time of pre-defined vibration and the frequency of occurrence of CSBM over 24 hours (figure 1). The number and percentage of CSBMs were higher in the active arm (p<0.0018) compared to sham arm (figure 1), and coincided with the timing of vibration as preprogrammed for the capsule (8-12 hours from administration 1st peak). In addition although there is sham response (natural circadian rhythm), it drops dramatically the next morning, (hours 34-36), while VC active arm shows greater activity during that time (24 hours from last vibration) (figure 2). In study 2, because of multiple vibration sessions, 2 peaks were seen: 1st peak around 8-12 hours followed by a 2nd peak around evening time (figure 3). Significant clinical correlation was found with multiple vibration sessions and CSBM (p<0.0357). Conclusion: VC significantly increases the number of CSBMs when compared to sham and this coincides with VC activation. This observation suggests that the mechanism of action of VC is to induce bowel movements through mechanical vibration of the colon, augmenting colonic biorhythm and peristalsis. This unique, non-pharmaceutical modality could be a novel approach for constipation.418_A Figure 1. Correlation between vibration time and frequency of CSBM - single vibration session418_B Figure 2. Vibration during 48 hours418_C Figure 3. Correlation between vibration time and frequency of CSBM - mult vibration sessions