Editorial: Vibrating capsule for severe chronic idiopathic constipation - severity lies in the eye of the beholder

Abstract

Chronic idiopathic constipation (CIC) is defined by criteria including infrequent and hard bowel movements, straining, use of digital manoeuvres to facilitate bowel movements, and other more subjective symptoms such as incomplete evacuation. The diverse pathophysiology underlying these symptoms makes CIC management challenging.

Lembo et al performed a post hoc analysis of a phase 3 trial that demonstrated improvement in CIC with a vibrating capsule (Vibrant^®, Vibrant Ltd).¹ In this analysis, they evaluated a subset of participants with severe CIC, defined as 0 complete spontaneous bowel movements (CSBMs) during the 2-week baseline period. Over 93% of subjects had an average increase of ≥1 CSBM during the 8 weeks of treatment relative to 40% with placebo. A significantly greater proportion of subjects receiving the vibrating capsule had an increase in CSBMs of ≥1, ≥2, or ≥3 per week over baseline for ≥ 6 out of 8 treatment weeks, relative to the placebo arm. The vibrating capsule was well tolerated with only mild reported adverse events that were similar between the two arms. These results suggest that the vibrating capsule may be yet another modality in this challenging patient population.

While data for these devices in CIC had been limited to small trials prior to the publication of the parent trial, there is an unmet need for more effective constipation treatments among those with severe CIC symptoms.² Importantly, this work showed both improved symptom response and quality of life over placebo in more severely affected individuals, an important treatment gap with limited pharmacologic data and absent non-pharmacologic data until now. Our experience suggests that patients are eager for non-pharmacologic options, especially for a condition where treatment satisfaction depends more on quality of life than pure efficacy.

When deciding on positioning of this therapy relative to our existing pharmacologic options, the details do matter. The standard FDA-recommended outcome for drug trials in CIC requires ≥3 CSBMs/week and an increase of ≥ 1 CSBM/week from baseline for at least 9 weeks of the 12-week treatment period; this device trial relied on the change in CSBM frequency rate over an 8-week period. Thus, caution is required when comparing non-pharmacologic devices to existing pharmacologic therapies.

Furthermore, “severe” CIC lacks a widely accepted definition—a single definition has not been uniformly applied across previous studies. Where pharmacologic data are available, prior studies have defined severe CIC as various combinations of CSBMs, symptom scores, physician assessment, or failure of other laxatives.^3–6 The frontline clinician’s perspective on what constitutes severe CIC probably varies across institutions and practice type (community versus academic). Similarly, an individual patient’s perspective on severity may be unique. Delineating these provider- and patient-specific factors will be necessary in working towards a uniform definition for severe CIC.

While the vibrating capsule produced significant improvement in bowel symptoms for patients with severe CIC with an excellent safety profile, challenges in the optimal positioning of CIC therapies remain. These include the heterogenous definitions of severity and differing requirements for proof of efficacy for drugs and devices.