Non-Invasive Nerve Stimulation Shows Promise for Younger IBD Patients

Transcutaneous auricular vagus nerve stimulation (ta-VNS) was safe and effective for both children and young adults with mild to moderate inflammatory bowel disease (IBD), a pilot study found.

Among 22 IBD patients treated with ta-VNS, 11 of the 17 with baseline fecal calprotectin (FC) scores greater than 200 experienced an FC reduction of more than 50% by week 16, reported Benjamin Sahn, MD, of Cohen Children's Medical Center in New Hyde Park, New York.

In addition, half of all Crohn's disease patients and 43% of ulcerative colitis patients achieved clinical remission by week 16, he explained at the virtual Advances in Inflammatory Bowel Disease meeting.

"We were not surprised as much as we were very excited by our results," Sahn told MedPage Today. "There is now a wealth of scientific evidence that the nervous system interacts with the immune system in numerous ways that has a critical impact on disease and health determinants."

Vagal nerve stimulation "can activate the 'inflammatory reflex,' a neural reflex that modulates innate and adaptive immunity in response to pro-inflammatory mediators," explained Sahn and colleagues in their poster presentation. Surgically implantable vagal nerve stimulation devices have been approved for certain conditions, such as stroke rehabilitation, and Sahn noted that positive results with these devices have been observed in patients with Crohn's disease and rheumatoid arthritis.

"We decided the safety profile of vagal nerve stimulation is so strong that investigating its effectiveness became too important," Sahn added. "We are the first investigators to report on the use of non-invasive, transcutaneous vagal nerve stimulation to treat humans with IBD."

Sahn's group evaluated 22 patients with IBD, initially randomizing 10 patients to receive once-daily stimulation with ta-VNS in their left external ear "targeting the cymba conchae" and 12 to a once-daily sham stimulation of their left calf for 5 minutes.

After 2 weeks, patients crossed over to the alternative treatment for an additional 2 weeks. Then all patients initiated ta-VNS at week 4 for 5 minutes, twice-daily for 12 weeks. Follow-up ended after 16 weeks.

Enrolled patients had been diagnosed with IBD at least 3 months before randomization, failed at least one conventional IBD therapeutic option, and had FC levels of 200 μg/g or above within 4 weeks of the study.

The primary outcome was ≥50% reduction in FC levels at week 16 compared to baseline.

Patients ranged from ages 10 to 21 years (average 14), and 55% were male. Ten patients had Crohn's disease and 12 had ulcerative colitis. About a third patients were on 5-aminosalicylates, 18% were on anti-integrins, and 18% were taking no medication at all.

Interestingly, Sahn's group found that improvement in FC and symptoms occurred earlier for ulcerative colitis patients compared to those with Crohn's disease.

"Non-invasive engagement of the inflammatory reflex can be an alternative to pharmacologic therapy in some patients," they concluded.

"This is a very interesting, perhaps fascinating study," said Russell Cohen, MD, of the University of Chicago, who was not involved in this study.

Despite calling the study design impressive, Cohen pointed out that week 2 results of the "sham" treatment were not reported on or otherwise not clearly distinguishable from the data graphs presented.

"As a result, the implication that the benefits were due to stimulation of the auricular root of the vagus nerve cannot be concluded," he told MedPage Today.

Comment