Investigating the Role of Ghrelin in Regulating Appetite and Energy Intake in Patients Following Bariatric Surgery (BARI-INSIGHT)

Summary

Bariatric surgery helps patients with severe obesity to lose weight, cures and prevents diseases linked to obesity and reduces the risk of death. Unfortunately, 1 in 5 patients do not respond well to surgery in terms of weight loss and health gains. Thus, maximising weight loss and health benefits after surgery is critical. This study aims to gain insight into the role that the appetite-stimulating hormone, ghrelin, plays in driving appetite and energy intake in patients with poor weight loss (≤ 20% total body weight) following bariatric surgery. This will guide future work to develop pharmacological treatments for obesity, both as standalone treatments and adjuncts to bariatric surgery.

Participants will be invited to attend the Clinical Research Facility at University College London Hospital for a screening visit and six study visits. Active ghrelin levels will be reduced by inhibiting ghrelin-o-acyl-transferase (GOAT), the enzyme needed to generate active ghrelin (acyl ghrelin, AG). Participants will be randomised to receive GLWL-01 (GOAT inhibitor) 300mg BD or placebo for a 10 day study cycle. The effect of AG reduction on appetite and energy intake will be evaluated through both fixed-energy and ad libitum meal tests on day 7 and 10, respectively. Measures of body weight and composition, appetite and food cravings will be performed in addition to biochemical profiling of circulating gut hormone, adipokine and cytokine levels. Targeted physical examinations and assessment of adverse events will be performed. Safety monitoring calls will be conducted 2 and 7 days after the last dose. Following a 6-10 week washout period, participants will cross over to receive either placebo or GLWL-01 300mg BD and undergo a second study cycle, with all measures repeated.

Conditions

• Obesity
• Bariatric Surgery Candidate
• Appetitive Behavior

Interventions

DRUG

GLWL-01

Small molecule inhibitor of Ghrelin-O-Acyltransferase (GOAT) to reduce levels of circulating acyl ghrelin. (Defined as a mechanistic study by MHRA; intervention not for therapeutic purposes in this study.)

OTHER

Placebo

Same as GLWL-01, but no active ingredient

Sponsors & Collaborators

• University College, London

  lead OTHER

Principal Investigators

• Rachel L Batterham, PhD FRCP · UCL

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

64 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-02-15

Primary Completion

2020-03-06

Completion

2020-03-13

Countries

• United Kingdom

Study Locations