Endoscopic Ablation Reduces ‘Hunger Hormone,’ Yields Weight Loss in Early Trial

— First-in-human study targets ghrelin production with mucosal ablation as obesity treatment

by Ed Susman , Contributing Writer, MedPage Today

May 21, 2024

WASHINGTON — Endoscopic gastric fundus mucosal ablation (GFMA) as a means of reducing production of the hunger-modulating hormone ghrelin was technically feasible and safe in a first-in-human study, and led to reductions in hunger and weight.

In the 6-month trial of 10 women with obesity, analysis of the primary endpoints showed that endoscopic GFMA reduced mean fasting ghrelin plasma levels and meal capacity as measured by maximum tolerated volume by more than 40% from baseline to study end (P=0.006 and P<0.005, respectively), reported Christopher McGowan, MD, of the True You Weight Loss clinic in Cary, North Carolina.

Furthermore, the patients in the so-called ABLATE WEIGHT trial had decreased hunger, improved confidence in being able to avoid overeating, and lost an average 7.7% of their body weight at 6 months (P<0.0009), he detailed in a presentation at the Digestive Disease Week annual conference.

McGowan, who performed all the procedures himself at his clinic, explained in his presentation that the “gastric fundus is a key regulator of appetite through hormonal and visceroceptive pathways” (specifically ghrelin production within the oxyntic mucosa and satiation via vagal feedback during prandial distention), but “currently, the only means of directly altering these pathways is surgical resection or bypass.”

As such, an endoscopic method to achieve this would represent a novel treatment for obesity.

Noting that the trial and the work is in its infancy, Syed Adeel Hassan, MBBS, of the University of Kentucky in Lexington, told MedPage Today that an endoscopic approach “could be a game-changer for weight-loss procedures.” He pointed out that more invasive weight-loss surgeries carry risks for bleeding and other complications, in addition to a long recovery time, while GFMA in the study was done in an office setting as an outpatient procedure.

But it remains to be seen how the weight-loss results with GFMA will pan out long-term, Hassan cautioned, and whether they will be on par or superior to Roux-en-Y gastric bypass or other invasive surgical techniques.

“We also have to be alert for complications in the long-term,” he said. “Any time you are ablating a hormone source, we need to see if there are consequences elsewhere in the body. We need to see a larger study with comparator treatments over a longer time to assess how well this will fit into weight-loss programs.”

In the study, GFMA was performed successfully in all 10 cases, with no serious adverse events (AEs), said McGowan. “All the AEs were grade 1 and were treated conservatively, often with over-the-counter gas-relief products,” he said. “All the patients experienced abdominal cramping or discomfort, and most complained of nausea.”

The prospective ABLATE WEIGHT study was a single-center, open-label trial that included 10 women (mean age 38.4 years) with an average body mass index of 40.5 (range 35.7-50). Average procedure duration was 84.4 minutes, and the average volume injected for submucosal lift was 240.3 mL.

For the primary endpoints, mean fasting ghrelin plasma levels decreased from 461.6 pg/mL at baseline to 254.8 pg/mL at 6 months while maximum tolerated volume, assessed during a standardized nutrient drink test, decreased from 807 mL to 467.3 mL.

Secondary endpoints included change in total body weight; change in appetite, hunger, and cravings using the DAILY-EATS questionnaire (a 0-10 scale); change in the ability to resist overeating via the Weight Efficacy Lifestyle Questionnaire Short Form (WEL-SF; a 0-80 scale); safety; and technical success.

Hunger scores decreased from 6.2 at baseline to 4.0 at 6 months (P=0.002) while scores on the Eating Drivers Index (hunger, appetite, cravings) decreased from 7.0 to 4.0 (P<0.001). Confidence to avoid overeating on the WEL-SF increased from 47.4 at baseline to 62.4 at study end (P=0.001).

AEs included abdominal cramping/discomfort in 100% of the women, nausea in 90%, gas in 30%, burping in 20%, along with vomiting, constipation, and aversion to savory foods (10% each).

McGowan said the study is a first step in evaluating the endoscopic procedure, and the goal is to eventually include a larger cohort of patients with longer follow-up, as well as an evaluation of GFMA combined with restrictive eating and endoscopic bariatric therapies. Future research also will look at wider ablative territories, including the gastric body, for enhanced remodeling.

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