Two companies – one Israeli, the other Chinese – developed a capsule to stimulate the colon from the inside by means of vibrations in chronic idiopathic constipation. These capsules should be swallowed three to five times a week. Appealing from a scientific perspective, says Prof. André Smout, emeritus professor of neurogastroenterology and motor skills (Amsterdam UMC). However, he does not yet see any application in clinical practice for this vibrating pill.
It sounds like an interesting idea: a swallowable, vibrating capsule for patients with chronic idiopathic constipation. But is it? Based on the first publications about this1,2 Smout wasn’t very convinced to say the least. He explains: “We have known for a long time that the gut can contract when mechanically stimulated. Therefore, the possibility of relieving constipation by massaging the abdomen has been examined and devices have also been developed that make the lower abdomen vibrate. And there is some evidence that physical exercise helps. But recently we also know that enterochromaffin cells in the large intestine contain the Piezo2 receptor, which is involved in tactile sensitivity to stimuli from the intestinal lumen. The presence of that receptor makes it plausible that stimulation of the gut from the inside rather than from the outside makes sense.”
However, based on those first studies, Smout was not yet convinced of the added value of internal stimulation with a swallowable, vibrating capsule. A study was published in 20153 which investigated the safety and effectiveness of the Israeli capsule in 26 patients. “A very good efficacy was concluded from this,” says Smout. “But that’s to be expected from an open, non-sham-controlled study.”
In 2020, results of larger and sham-controlled studies with the Israeli capsule will be published. These are two randomized clinical trials, which were conducted in the United States in 2017 and 2018. The primary endpoint – increase in the number of defecations – was not met. But a post-hoc analysis of the pooled data shows a difference in the extent to which defecation occurs at the most anticipated times: in the morning and after the evening meal. However, that alone does not prove that the capsule leads to additional defecations.
More frequent CSBMs
Smout’s view on the possible value of a capsule is nuanced by a recent in Gastroenterology published abstract3 that, based on the same research design, shows that the capsule is effective. “This clearly shows a higher incidence of CSBMs (‘complete spontaneous bowel movements’) without the use of laxatives than when the capsule is not vibrating,” he says. “However, as mentioned, it is still an abstract, so the findings have not yet been peer-reviewed.”
Recently, the results of a double-blind, sham-controlled study with the Chinese vibrating capsule were also published.4 The percentage of patients whose capsule use resulted in at least one additional CSBM per week was 64% in the group that received a true vibrating capsule and 36% in the sham group. This difference was statistically significant (p = 0.0050).
Yet important questions remain unanswered. Smout: “These previous studies showed that the differences in CSBMs between vibrating and non-vibrating capsules are not very large. In any case, the capsule certainly does not seem like a panacea with which constipation disappears. In addition, the effect of the capsule has not yet been compared to that of a laxative. We also do not read why patients believe that a laxative does not provide sufficient results for them.”
Safety not the problem
As far as the safety of the application of a capsule is concerned, Smout does not expect any major problems, provided certain things are ruled out in advance. “We are also familiar with endoscopic capsules and they are safe to use,” he says. “However, with the capsule in question, you have to be sure that there is no narrowing in the gastrointestinal tract in which the capsule can get stuck. Severe colonic diverticulosis is still a question mark for me. It is conceivable that the capsule could become entangled in such a diverticulum.”
Trilactiviteit
The capsule starts to vibrate several hours after ingestion. In relation to this, two optimal starting times are mentioned in the studies: 06.00 and 14.00. “These moments are related to the physiological stimulus to defecate,” says Smout. “There are two forms of contractions in the colon. One is kneading, all day long. The other is the ‘high-amplitude propagating contraction’ which occurs 6 to 10 times a day to push a large amount of stool into the rectum. The researchers have apparently realized that it is important to vibrate the capsule at those times when the body itself can be expected to be active. That is smart thinking.”
The Israeli publications talk about vibrating the capsule once every 20 seconds. “There is some logic in that,” says Smout, “because the large intestine contracts a maximum of 3 to 6 times per minute. However, the Israeli study says nothing about the frequency and amplitude of that vibration. The Chinese Study with the Competing Product4 provides a little more clarity on this. The capsule vibrates 12 times per minute, adjustable between 3 and 9 Hertz. The added value of one over the other is unclear. Both capsules should actually be compared in a study. But given that they are products of competing companies, that won’t happen.”
Unclear perspective
In conclusion, Smout does not expect that the capsule will soon be eligible for reimbursement within the package of insured care. “We don’t know what the capsule will cost yet,” he says, “but it’s a non-reusable device, so it will be more expensive than a laxative. The added value of the capsule for the patient compared to laxative measures must then be really evident. There are also other treatment options for really treatment-resistant constipation, namely daily intestinal rinsing and, in extreme cases, total removal of the colon. These clearly have adverse effects on the quality of life and you would therefore prefer to avoid them. But for both I don’t see the capsule as a realistic alternative. Those two options are ideal for the heaviest patient category, and neither the Israeli nor the Chinese capsule have been tested on that group. In short: the idea is certainly interesting from a scientific point of view, but the road to the clinic is still uncertain.”
References:
- Ron Y, Halpern Z, Safadi R, et.al. Safety and efficacy of the vibrating capsule, an innovative non-pharmaceutical treatment modality for chronic constipation. Neurogastroenterol Motil. 2015:27;99-104.
- Rao S, Lembo A, Chey W, et.al. Effects of the vibrating capsule on colonic circadian rhythm and bowel symptoms in chronic idiopathic constipation. Neurogastroenterol Motil. 2020:32:e13890.
- Rao S, Quigley E, Chey W, et.al. Efficacy and safety of Vibrant capsule for chronic idiopathic constipation (CIC): randomized, double-blind, multicenter, placebo-controlled phase III trial. Gastroenterol. 2022:162(7)Suppl;S-124. Doi 10.1016/S0016-5085(22)60302-0.
- Zhu J, Qian Y, Pan J, et.al. Efficacy and safety of vibrating capsule for functional constipation (VICONS): A randomized, double-blind, placebo-controlled multicenter trial. eClinicalMedicine. 2022;47:101407.