Transcutaneous vagus nerve stimulation does not alter gastrointestinal function in diabetic autonomic neuropathy
Aims: To examine the effect of transcutaneous vagus nerve stimulation(tVNS)on magnetic resonance imaging (MRI)-assessed gastrointestinal function.
Methods: This is a sub-study of the DAN-VNS study, a randomized, sham-controlled, double-blind parallel group trial examining the effect of tVNS in subjects with diabetes, gastrointestinal symptoms and diabetic autonomic neuropathy. Subjects were randomized to one week of active or sham tVNS. A meal-stimulated pan-alimentary MRI scan protocol was performed after the one-week stimulation. Gastric, small bowel, and colonic volumes, gastric half-emptying time, small bowel motility, and gastrointestinal symptom scores were evaluated.
Results: Eighteen and sixteen patients were randomized to active and sham treatment. When comparing active tVNS and sham treatment, no differences were observed in MRI-assessed gastric, small bowel, and colonic volumes at any post-meal time points after one week of treatment. Gastric half-emptying time was not different between active and sham groups (105±37min vs. 101±36min, p=0.77). Increased small bowel motility was observed 105min postprandially in the active group compared to sham (184±53au. vs. 138±28au., p=0.04), without differences on the remaining time points. Moreover, symptom scores were unaffected by treatment, and no correlations between symptom scores and MRI measurements were found.
Conclusions: This study showed no effect on MRI-based volumetric and motility measurements of the gastrointestinal tract after one week of tVNS treatment compared to sham in diabetes complicated by DAN and gastrointestinal symptoms.
Comments. The previously published DAN-VNS study had shown no effect of tVNS on gastrointestinal symptoms in people with DAN, this sub-study adds the novel information of inefficacy also on the MRI-measured gastrointestinal function. This study has the strengths of using a more reliable MRI-based protocol that was previously explored in healthy controls and patients with diabetes, including intra-subject variability, and of providing a pan-alimentary assessment more suitable than segment-based methods to the pan-enteric nature of diabetic gastroenteropathy. The wireless motility capsule, which also allows pan-alimentary measurements, is no longer available and the new Motilis 3D-Transit system is of limited use in a few research centers. MRI provide detailed visualization of gut motility and volumes, although widespread utilization is hampered by costs and low availability. Moreover, the actual magnitude of tVNS is relatively unknown due to self-administration and indirect transcutaneous stimulation technique using a hand-held device. Additionally, this MRI sub-study including one third of the full cohort was not powered to detect small effects of tVNS on the MRI-derived parameters. While this exploratory study was relatively large for MRI research, the lack of changes suggests that any potential effects are likely small and of limited clinical relevance. Moreover, the high BMI observed in this study might have underestimated the small bowel volumes due to few slices used in the small bowel MRI sequence. The MRI scans, evaluating gastric and colonic volumes, had varying numbers of slices, which depend on body size. Overall, the MRI protocol might need further standardization and fine-tuning before being further integration in research and clinical use.
Eleni Karlafti
Reference.Kahlke DG, Mark EB, Bertoli D, Al-Abdali ASA, Kornum DS, Kufaishi H, Krogh K, Knop F, Hansen CS, Brock B, Brock C, Drewes AM, Frøkjær JB. Transcutaneous vagus nerve stimulation does not affect gastrointestinal function in subjects with diabetic autonomic neuropathy. Scand J Gastroenterol. 2025 Nov;60(11):1129-1139. doi: 10.1080/00365521.2025.2572620. Epub 2025 Oct 10. PMID: 41070997.
