In a groundbreaking first-in-human trial, the ablation of the gastric fundus, aimed at curbing the production of the “hunger hormone” ghrelin, has led to promising outcomes including decreased appetite and notable weight loss among participants.
Dr. Christopher McGowan, a prominent gastroenterologist and senior investigator of the study conducted at True You Weight Loss in Cary, North Carolina, shared that patients experienced a significant decrease in hunger, appetite, and cravings, coupled with a newfound sense of control over their eating habits. This transformation in their relationship with food was highlighted during a press briefing at Digestive Disease Week (DDW) 2024, where the research findings were unveiled.
The rationale behind targeting the gastric fundus lies in its composition, housing approximately 80%-90% of ghrelin-producing cells within its mucosal lining. When individuals undergo dieting or weight loss, ghrelin levels surge, intensifying hunger pangs and thwarting sustained weight management efforts. Until now, surgical interventions such as fundus removal or bypass were the sole proven methods to diminish ghrelin levels, as weight-loss medications primarily focus on alternative hormonal pathways like glucagon-like peptide 1 (GLP-1).
The trial, involving ten women with an average age of 38 and a mean body mass index of 40.2, witnessed the use of endoscopic fundic mucosal ablation via hybrid argon plasma coagulation. This minimally invasive procedure, conducted under general anesthesia in an outpatient setting, demonstrated efficacy with an average duration of less than one hour, providing convenient access to the fundus.
At the six-month mark, compared to baseline measurements, participants exhibited promising results:
- A 45% reduction in circulating ghrelin levels.
- A 53% decline in ghrelin-producing cells within the fundus.
- A 42% decrease in stomach capacity.
- A 43% alleviation in hunger, appetite, and cravings.
- An impressive 7.7% reduction in body weight.
Remarkably, mean ghrelin concentrations plummeted from 461.6 pg/mL at baseline to 254.8 pg/mL over the study period. Additionally, participants’ tolerance to nutrient intake significantly decreased, with the maximum tolerated volume dropping from a mean of 27.3 oz to 15.8 oz at the six-month follow-up.
Assessment through various questionnaires further corroborated these findings, revealing substantial improvements in hunger scores, eating behavior, and overall well-being.
Notably, endoscopic evaluation at the six-month mark revealed the contraction and healing of the gastric fundus, with an unexpected yet advantageous discovery of fibrotic tissue, contributing to a reduction in fundus expandability—a crucial factor in inducing satiety.
The safety profile of the procedure remained favorable, with participants experiencing transient symptoms such as gas pressure, mild nausea, and cramping, lasting 1-3 days post-treatment. Dr. McGowan emphasized the paramount importance of maintaining safety during the procedure, employing techniques to ensure minimal penetration into deeper layers of the stomach and highlighting the absence of nerve receptors within the stomach lining, thus mitigating pain.
Dr. McGowan underscored the urgent need for diverse interventions to combat the obesity epidemic, affecting nearly half of adults in the United States. Gastric fundus ablation emerges as a promising therapeutic option, potentially benefiting millions of individuals grappling with obesity.
While the role of gastric fundus ablation in isolation or in conjunction with existing weight-management interventions such as bariatric surgery or medication remains to be elucidated, its potential as a standalone or adjunctive treatment warrants further exploration.
This innovative approach could offer a viable alternative for individuals who are unable or unwilling to undergo long-term medication regimens, presenting a one-time intervention with enduring effects. Additionally, it holds promise as a transitional aid for individuals discontinuing GLP-1 medications, facilitating weight maintenance post-treatment.
Dr. McGowan concluded by highlighting the potential synergy of combining gastric fundus ablation with other endoscopic interventions such as the endoscopic sleeve, offering a comprehensive approach that addresses both anatomical and hormonal aspects of obesity management.
Disclosure: Dr. McGowan reported consulting for Boston Scientific and Apollo Endosurgery.
- : public
