Introduction

Capsule colonoscopy and Pan-intestinal Capsule Endoscopy (PCE) are well-established diagnostic procedures. However, the optimal bowel preparation regimen remains undefined, with pooled adequate cleansing rates reaching only 72.5%¹. While ultra-low volume preparations (≤1L) have demonstrated efficacy in conventional colonoscopy², their effectiveness in capsule-based modalities has yet to be determined.

Aims & Methods

In this prospective, randomized, researcher-blind, single center trial, we compared the efficacy of two ultra-low volume bowel preparation regimens, 1L Polyethylene Glycol Plus Ascorbic Acid (PEG-Asc) and 1L Sodium Picossulfate with Magnesium Citrate (SPMC). Patients referred for capsule-based procedures were randomized in a 1:1 ratio to receive either PEG-Asc or SPMC. The primary endpoints were the rates of complete examinations, adequate bowel preparation, and excellent right colon cleansing.

Results

A total of 117 patients were included, referred for capsule colonoscopy due to incomplete colonoscopy (76.1%) or for PCE to assess luminal inflammation (17.9%) or anemia (6%). Overall, 61.5% were female, with a mean age of 61.3 ± 16 years. The complete examination rate was 71.8%, with no significant difference between groups (PEG-Asc 72.9% vs. SPMC 70.7%; p = 0.792). Adequate bowel preparation was achieved in 62.4% of cases, which was significantly more frequent in the PEG-Asc group (72.9%) compared to SPMC (51.7%; p = 0.018). Among complete procedures, excellent right colon cleansing was observed more often with PEG-Asc (34.1%) than with SPMC (7.3%; p = 0.003).

Conclusion

The completion and adequate preparation rates remain suboptimal in the capsule colonoscopy and PCE procedures. In this study, both ultra-low volume purgative solutions demonstrated comparable efficacy in achieving complete examinations, but the PEG-Asc resulted in significantly better overall preparation quality and superior right colon cleansing compared to SPMC. These findings suggest that PEG-Asc may be the preferred ultra-low volume regimen for optimizing bowel visualization in capsule-based examinations.

References

1. Rosa, B., Donato, H., Cúrdia Gonçalves, T., Sousa-Pinto, B. & Cotter, J. What Is the Optimal Bowel Preparation for Capsule Colonoscopy and Pan-intestinal Capsule Endoscopy? A Systematic Review and Meta-Analysis. Dig. Dis. Sci. 68, 4418–4431 (2023).
2. Arieira, C. et al. Bowel cleansing efficacy for colonoscopy: prospective, randomized comparative study of same-day dosing with 1-L and 2-L PEG + ascorbate. Endosc. Int. Open 09, E1602–E1610 (2021).

Introduction

A dysfunctional intestinal mucosal barrier is a key pathophysiological hallmark and driver of a broad range of gastrointestinal diseases including celiac disease and inflammatory bowel disease. To date, there are no adequate treatment strategies to ameliorate impaired barrier function.
IMU-856 is an orally available and systemically acting small molecule modulator of sirtuin 6 (SIRT6), a histone/non-histone protein deacetylase which serves as a transcriptional regulator of intestinal barrier function and regeneration of bowel epithelium. IMU-856 may represent a new approach to treat gastrointestinal diseases with compromised barrier function.

Aims & Methods

This was a first-in-human, double-blind, randomized, placebo-controlled clinical trial of IMU-856 in healthy volunteers and patients with celiac disease. In the multiple ascending dose part, healthy human subjects were dosed once-daily for 14 consecutive days with IMU-856 at three different dose levels or placebo. Additionally, the Phase 1/1b study was designed to assess safety and tolerability of IMU-856 at two different dose levels in patients with celiac disease during periods of gluten-free diet and a 15-day gluten challenge. Further objectives included pharmacokinetics and the assessment of histological changes. Biomarkers reflecting intestinal enterocyte mass and function, nutrient absorption, and enteroendocrine hormones like GLP-1 were analyzed to assess potential effects on gut health.

Results

IMU-856 was safe and well-tolerated with a benign adverse event profile and pharmacokinetics that allow once-daily dosing. Treatment with IMU-856 protected against gluten-induced histologic deterioration, improved the health and metabolic function of intestinal enterocytes as measured by nutrient uptake and citrulline [1], and had positive effects on enteroendocrine cells increasing endogenous GLP-1 levels in a dose-dependent manner.

Conclusion

IMU-856 is a safe, highly selective and potent epigenetic modulator, improving the intestinal barrier function in patients with celiac disease undergoing a gluten challenge.
Positive effects of IMU-856 on gut hormones and various biomarkers for overall gut health including intestinal function and integrity were observed. Therefore, IMU-856 may offer extensive potential for treatment of gastrointestinal diseases with compromised intestinal barrier function and metabolic diseases.

References

1. Daveson AJM, Stubbs R, Polasek TM, Isola J, Anderson R, Tye-Din JA, et al. Safety, clinical activity, pharmacodynamics, and pharmacokinetics of IMU-856, a SIRT6 modulator, in coeliac disease: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial.

Disclosure

AS, MW, EP: employees of Immunic AG, option and shareholders of Immunic, Inc.
IPO, JF, IK, SE: employees of Immunic AG, option and/or shareholders of Immunic, Inc.
HK: employee of Immunic AG, shareholder of Immunic, Inc., co-inventor of patents for the drug in investigation
DP: option holder of Immunic, Inc.
DV, AM: employees of Immunic AG and Immunic, Inc., shareholders of Immunic, Inc., co-inventors of patents for the drug in investigation