Introduction
SBS-IF is a severe organ failure with long-term parenteral support (PS) dependence. In the first years after extensive surgery, spontaneous structural (elongation of intestinal villi and crypts) and functional (incl. motility) intestinal changes occur, stimulating a more efficient nutrient and fluid absorption in the remnant bowel. GLP-2 analogs are hypothesized to boost intestinal adaptation resulting in increased intestinal absorption and reduced PS needs. Apraglutide (APRA) is a long-acting GLP-2 analog in development for SBS-IF. We investigated the effect of APRA at 52 weeks (W) on bowel morphology and motility based on magnetic resonance imaging (MRI).
Aims & Methods
STARS Nutrition is a 52-W multicenter, open-label, phase 2 study in adult SBS-IF-CiC pts receiving weekly subcutaneous APRA injections (5mg). We hypothesized that APRA treatment would lead to thickening of the intestinal mucosa, intestinal lengthening, reduced bowel dilatation and reduced intestinal motility. Therefore, MRI scans of the abdomen, incl. cine sequences, after oral intake of a mannitol solution (600mL) were performed at baseline and at 4W, 24W and 48W of treatment. Morphology parameters were measured on static MRI sequences; GI Quant software was used to quantify motility on cine MRI sequences. Data are presented as median (IQR). Nominal p-values are calculated using Wilcoxon matched-pairs signed rank tests with significance set at 0.05.
Results
Nine pts were included and comprise the full study population. While the numerically increased colon length failed to reach significance, small bowel length increased significantly from 29.7 to 40.7 cm (p=0.012) at 48W. Duodenal wall thickness increased by 0.8 (0.2;1.2) mm (p=0.020). There were no diameter changes in the small bowel nor colon. Changes in motility were evaluated using data from 7 pts, due to missing data. Over time, small bowel motility gradually reduced, albeit not significant. Motility in the proximal colon was significantly reduced at 48W. In the distal colon, decreased motility was observed at 4W and 24W, but returned to baseline level at 48W.
Conclusion
Using static and cine MRI sequences in pts with SBS-IF-CIC, STARS Nutrition shows that APRA treatment was associated with small bowel lengthening and increased duodenal wall thickness suggesting an intestinotrophic effect. Both effects may contribute to an increased surface area for absorption. The reduced motility, especially in the proximal colon may reduce transit time, allowing more time for absorption of nutrients, fluids and electrolytes; and reduced fecal output. Whether bowel lengthening results from a direct effect of APRA vs. changes in motility with passive elongation is subject of further investigation.
Disclosure
Astrid Verbiest, Mark Krogh Hvistendahl, Ragna Vanslembrouck, Ronald Peeters, Riccardo Sartoris – nothing to declare.
Palle Bekker Jeppesen – received grants/research support/honoraria or consultation fees from Agomab, Albumedix A/S, ArTara Therapeutics, Bainan Biotech, Baxter, Coloplast, Ferring, Fresenius Kabi, GLyPharma, Naia Pharma, NPS Pharmaceuticals, NorthSea Therapeutics, Shire, Takeda, The Novo Nordisk Foundation, Therachon, VectivBio and Zealand Pharma.
Francisca Joly – has received grants/research support/honoraria or consultation fees from Agomab, Baxter, Fresenius Kabi, Nestlé Health Sciences, BBraun, Theradial, Mayoli, Biocodex, mobile3e Consulting, Carembouche, NPS Pharmaceuticals, NorthSea Therapeutics, Shire, Takeda, Therachon, VectivBio and Zealand Pharma.
Tim Vanuytsel – has served on the speaker bureau for Abbott, Agomab, Baxter, Biocodex, Dr. Falk Pharma, Fresenius Kabi, Ipsen, Menarini, Microbiotica, MyHealth, Remedus, Takeda, Truvion, VectivBio and Zealand Pharma. TV has provided clinical advice to Baxter, Danone, Dr. Falk Pharma, MyHealth, NorthSea Therapeutics, Shire, Therachon, Takeda, VectivBio, Zealand Pharma. TV has received research grants from Danone, MyHealth, Takeda and VectivBio.
Federico Bolognani, Carrie Li and Nader N. Youssef – employees of VectivBio/Ironwood.
This research was supported by VectivBio AG/Ironwood.
