Gastric fundus ablation targets hunger hormone for weight loss

Ablating the gastric fundus to reduce the production of the hunger hormone ghrelin helps women curb their appetite and lose body weight in the ABLATE-WEIGHT first-in-human trial.

Previously, the only way to reduce ghrelin was to surgically remove or bypass the fundus. Latest weight loss medications target a different hormonal pathway – glucagon-like peptide 1 (GLP-1).

“What we’ve learned from the GLP-1 medications is the profound impact of reducing hunger,” said senior study investigator Dr Christopher McGowan, a gastroenterologist and medical director of True You Weight Loss in Cary, North Carolina, US at DDW 2024. “That's how patients describe the effect — that it changes their life and quality of life, and that is quite important.’’

In the current trial, 10 women (mean age 38.4 years, mean BMI 40.5) underwent endoscopic ablation of the mucosal lining of the fundus – using hybrid argon plasma coagulation in an ambulatory setting, while under general anaesthesia. The average volume injected for the submucosal lift was 240.3 mL. The average procedure time was 84.4 minutes. [DDW2024, abstract 516]

“Patients had a decrease in hunger, appetite, and cravings, and an increase in eating control,” reported McGowan, who performed all the procedures at his clinic. “Their relationship with food had changed.”

He explained that targeting the gastric fundus makes sense because its mucosal lining contains 80–90 percent of the cells that produce ghrelin. “When we lose weight or go on a diet, the ghrelin levels go up, making us even hungrier. Sustaining weight loss becomes more difficult.”

Multiple benefits seen

Mean fasting ghrelin plasma concentrations and meal capacity, as measured by maximum tolerated volume, reduced by >40 percent from baseline to study end (p=0.006 and p<0.005, respectively), reported McGowan.

Hunger scores decreased (p=0.002), and so did the scores on the Eating Drivers Index (hunger, appetite, cravings; p<0.001). On top of that, the women reported improved confidence in being able to avoid overeating and lost an average of 7.7 percent of their body weight at 6 months (p<0.0009).

Yet more questions remain

“It is fascinating that the hormone ghrelin decreased just by ablating,” commented Dr Loren Laine from Yale School of Medicine and chair of DDW 2024. “The investigators used the same device that we use to treat bleeding ulcers or lesions in the stomach and applied it broadly over the whole upper part of the stomach.”

She said weight loss is an endpoint patients care about the most. The 7.7 percent weight loss was not impressive, but the trial had only 10 patients. “We are interested to see whether the total body weight loss will be different in a larger cohort of patients with a longer follow-up. Another question is whether the gastric fundal accommodation would have any side effects such as dyspepsia, or whether there would be complications in the long term.”

Safety matters

Repeat endoscopy at 6 months showed that the gastric fundus contracted and healed. An unexpected and beneficial finding was the fibrotic tissue, which made the fundus less able to expand, McGowan said. A smaller fundus “is critical for feeling full,” he added.

No serious adverse events were reported. Participants experienced abdominal cramping or discomfort, and some complained of nausea, stomach gas, and burping and were treated conservatively.

“The key here is preserving safety,” emphasized McGowan. “This is why we injected a fluid cushion before ablating, so we’re not entering any deeper layers of the stomach. Importantly, there are no nerve receptors within the stomach lining, so there’s no pain from this procedure.”

A new treatment option?

“We need every tool possible to address obesity, which is affecting 1 in 2 adults. We know that obesity is not a matter of willpower. It is a disease,” said McGowan. “Gastric fundus ablation should represent a new treatment option for obesity.”