Investigating the Role of Ghrelin in Regulating Appetite and Energy Intake in Patients Following Bariatric Surgery (BARI-INSIGHT) (BARI-INSIGHT)
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|ClinicalTrials.gov Identifier: NCT03641417|
Recruitment Status : Recruiting
First Posted : August 22, 2018
Last Update Posted : April 24, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Obesity Bariatric Surgery Candidate Appetitive Behavior||Drug: GLWL-01 Other: Placebo||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||Double blind, placebo-controlled, within-subject, crossover mechanistic study|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||BARI-INSIGHT: A Double-blind, Placebo-controlled, Within-subject, Cross-over Mechanistic Study Investigating the Role of Ghrelin in Regulating Appetite and Energy Intake in Patients Following Bariatric Surgery|
|Actual Study Start Date :||February 8, 2019|
|Estimated Primary Completion Date :||November 30, 2019|
|Estimated Study Completion Date :||March 30, 2020|
Oral administration of GWL-01 300mg BD for 10 days
Small molecule inhibitor of Ghrelin-O-Acyltransferase (GOAT) to reduce levels of circualting acyl ghrelin.
(Defined as a mechanistic study by MHRA; intervention not for therapeutic purposes in this study.)
Placebo Comparator: Placebo
Identical oral capsules with no active ingredient, administered BD for 10 days
Same as GLWL-01, but no active ingredient
- Within-subject acute energy intake [ Time Frame: Final day of each study cycle, Day 10 ]Evaluate the effect of reduced circulating AG on within-subject acute energy intake assessed during an ad libitum meal.
- Fasted appetite scores [ Time Frame: Day 7 of each study cycle ]in response to a fixed meal assessed using visual analogue scales (VAS).
- Area-under-the-curve for appetite scores [ Time Frame: Day 7 of each study cycle ]in response to a fixed meal assessed using visual analogue scales (VAS).
- Macronutrient selection [ Time Frame: Daily during each study cycle ]assessed using a 24-hour diet diary and food selection during the ad libitum meal.
- Subjective aspects of appetite [ Time Frame: Final day of each study cycle, Day 10 ]specifically hunger, fullness, pleasantness to eat and nausea. Assessed using VAS and food craving questionnaires.
- 24-hour energy intake [ Time Frame: Final day of each study cycle, Day 10 ]assessed using a 24-hour diet diary, completed daily during GLWL-01 and placebo study arms.
- Gut hormones levels [ Time Frame: Day 7 of each study cycle ]Circulating levels of gut hormones in response to a fixed meal.
- Adipokine levels [ Time Frame: Day 7 of each study cycle ]Circulating levels of adipokines in response to a fixed meal
- Body weight [ Time Frame: Final day of each study cycle, Day 10 ]assessed using a bioelectrical impedance analyser (BIA).
- Body composition [ Time Frame: Final day of each study cycle, Day 10 ]assessed using a bioelectrical impedance analyser (BIA).
- Inflammatory markers and cytokines [ Time Frame: Final day of each study cycle, Day 10 ]Evaluate the effect of reduced circulating AG on circulating inflammatory markers and cytokines.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03641417
|Contact: Rachel L Batterham, PhD FRCP||0044 email@example.com|
|Contact: Roxanna Zakeri, MBBS MA MRCS||0044 firstname.lastname@example.org|
|University College London||Recruiting|
|London, United Kingdom|
|Contact: Roxanna Zakeri, MBBS MA MRCS email@example.com|
|Principal Investigator: Rachel L Batterham, PhD FRCP|
|Sub-Investigator: Roxanna Zakeri, MBBS MA MRCS|
|Principal Investigator:||Rachel L Batterham, PhD FRCP||UCL|