Duodenal Mucosal Resurfacing Shows Early Promise in Diabetes

Marlene Busko

June 12, 2016

NEW ORLEANS — In a first-in-human, single-arm study, 39 patients in Chile with type 2 diabetes who underwent endoscopic duodenal mucosal resurfacing, known as the Revita procedure (Fractyl), had better levels of metabolic markers at 6 months with no serious lasting adverse effects, researchers report.

If these promising early findings are reproduced in further, larger studies with a sham control arm, clinicians may someday be able to offer diabetic patients this minimally invasive treatment — which seems to provide potential improvements in diabetes similar to those seen with gastric-bypass surgery.

Alan D Cherrington, PhD, professor of medicine and molecular physiology and biophysics at Vanderbilt University, Nashville, Tennessee, presented these preliminary findings here at the American Diabetes Association (ADA) 2016 Scientific Sessions,

Duodenal mucosal resurfacing is an investigational endoscopic procedure that thermally ablates duodenal mucosa, and it received the CE Mark in Europe in April, based on the results of this study; these latest data from the trial take a closer look at the effect on metabolic markers.

To date, the mechanism of action remains unknown. However, a large international follow-up trial, REVITA 1, which is currently enrolling patients and has already collected 12-week safety and efficacy data on 28 patients, should help provide more information, said Dr Cherrington.

"The hope is that by learning more about why this works, we can develop a fairly simple approach to do this," he told Medscape Medical News. At the moment, the procedure is "promising but by no means proven," he cautioned.

"Certainly the data are striking," session chair Meredith A Hawkins, MD, from Albert Einstein College of Medicine, the Bronx, NY, commented to Medscape Medical News.

Clinicians may "shudder to think of the impact of gastric surgery on patients, so the concept of a much less invasive procedure that would be able to have such dramatic effects…is very intriguing," she said.

"Moreover, it will be interesting to see whether further research can shed light on the mechanism and see whether the procedure alters gut hormones or the microbiome or some other factors."

Better Levels of Metabolic Markers at 6 Months

It is not clear how thermal ablation of a section of the duodenal mucosal surface leads to improved levels of glycemic markers, but this may be related to reduced nutrient contact with duodenal mucosa after this procedure, as seen after gastric-bypass surgery, Dr Cherrington explained.

This line of research was partly inspired by the BARRX ablation procedure of abnormal esophageal tissue in patients who have Barrett's esophagus, he added. The original research was done in a pig model.

This first-in-human study enrolled 44 patients with type 2 diabetes at the same center, and 39 patients underwent the procedure. To be eligible, patients had to have an HbA1c of 7.5% to 12% while taking one or more antidiabetic agents.

The patients had a mean age of 53, and about two-thirds (64%) were male. On average, they had a body mass index (BMI) of 30.8 and an HbA1c of 9.6%; they had had diabetes for an average of 5.7 years.

About a third (11) of the patients  had a short, 3.4-cm section of the duodenum ablated, and the other 28 patients had a longer, 9.3-cm section of the duodenum ablated, in a 1-hour procedure performed under anesthesia by a gastroenterologist.

After the procedure, the patients were put on a low-calorie diet for 2 weeks and transitioned from consuming liquids to pureed foods.

The procedure was well tolerated; patients had few adverse events during 6 months of follow-up, which all resolved with treatment.

At 6 months, the average HbA1c was reduced by 1.2% from baseline (P < .001). The reductions in HbA1c were greater in the patients who had received an ablation of a longer section of the duodenum.

The HbA1c reductions occurred across a range of baseline HbA1c and were evident despite reduced use of diabetes medications.

"While further examination of duodenal mucosa resurfacing efficacy, safety, and clinical utility is needed, this study demonstrates the promise of this novel, endoscopic, duodenum-directed treatment of type 2 diabetes," Dr Cherrington summarized.

The trial was sponsored by Fractyl. Cherrington is on advisory panels for Biocon, Fractyl, Merck, Metavention, NuSirt Biopharma, Sensulin, and Zafgen. He is a consultant for Eli Lilly, Silver Lake, Islet Sciences, Novo Nordisk, Profil Institute for Clinical Research, Thermalin Diabetes, Thetis Pharmaceuticals, vTv Therapeutics, ViaCyte, and Viking. He receives research support from Eli Lilly, Merck, Metavention, Novo Nordisk, Silver Lake, and Thermalin Diabetes and holds shares for Fractyl, Metavention, Sensulin, Thetis Pharmaceuticals, and Zafgen. Disclosures for the coauthors are listed in the abstract.

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American Diabetes Association 2016 Scientific Sessions; June 10, 2016; New Orleans, Louisiana. Abstract 60-OR/60

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