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

NCT03641417 | Completed DMC

• 1 other identifier: 17/0887
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Obesity; Bariatric surgery; Appetite; Ghrelin; Energy intake; Gut hormones; Adipokines

Outcome Measures

Primary Outcomes (1)

• Within-subject acute energy intake

  Evaluate the effect of reduced circulating AG on within-subject acute energy intake assessed during an ad libitum meal.

  Final day of each study cycle, Day 10

Secondary Outcomes (10)

• Fasted appetite scores

  Day 7 of each study cycle

• Area-under-the-curve for appetite scores

  Day 7 of each study cycle

• Macronutrient selection

  Daily during each study cycle

• Subjective aspects of appetite

  Final day of each study cycle, Day 10

• 24-hour energy intake

  Final day of each study cycle, Day 10

Study Arms (2)

GLWL-01

EXPERIMENTAL

Oral administration of GLWL-01 300mg BD for 10 days

Drug: GLWL-01

Placebo

PLACEBO COMPARATOR

Identical oral capsules with no active ingredient, administered BD for 10 days

Other: Placebo

Interventions

GLWL-01 DRUG

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.)

GLWL-01

Placebo OTHER

Same as GLWL-01, but no active ingredient

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults aged 18 to 64 years inclusive.
• Minimum 1 year since primary RYGB or primary SG.
• Poor weight-loss (≤20% total body WL) not attributable to a surgical or psychological cause.
• Suboptimal nutrient-stimulated AG level assessed by a screening meal test. Suboptimal ghrelin response is defined as AG:DAG ratio (expressed as a percentage) of \>10% and/or failure to suppress AG (i.e. \<20%) in response to a standard 500kcal liquid meal.
• Weight-stable for at least 3 months prior to screening, determined by ≤5 % variation in body weight over this time.
• BMI ≤60 kg/m2
• Females of childbearing potential and males must be willing to use highly effective methods of contraception, with two methods preferred, from the time consent is signed until 8 weeks after treatment discontinuation (Appendix 2).
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for trial treatment. NOTE: Subjects are considered not of child bearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
• Able to read and write in English.
• Willing and able to provide written informed consent and comply with the study protocol.

You may not qualify if:

• Had a primary bariatric surgery procedure other than gastric bypass and sleeve gastrectomy, or revisional bariatric surgery of any operation type.
• Participation in other clinical intervention trial at any time during recruitment and study execution.
• Participation in a clinical trial within 30 days (defined as last dose of study drug) prior to GLWL-01 first dose.
• Eli Lilly and Company or GLWL Research Inc. employees, investigators or site personnel directly affiliated with this study, and their immediate family. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
• Weight exceeding 200kg (due to limitations of body composition analyser employed in the BARI-OPTIMISE Trial)
• Pregnant or lactating mothers.
• Known or suspected hypersensitivity to GLWL-01 450mg 300mg and placebo or any of the excipients involved in their formulation.
• Active diabetes mellitus, type 1 or 2
• a) Patients with complete remission of diabetes are however eligible. Complete remission is defined as return to normal measures of glucose metabolism (HbA1c \<6.5%, fasting glucose \<5.6 mmol/l) of at least 1 year's duration in the absence of active pharmacological therapy or ongoing procedures.
• History of clinically overt uncontrolled or untreated endocrine illness such as pituitary, adrenal or thyroid disease.
• Clinically significant cardiovascular abnormality:
• Unstable hypertension, clinically significant ECG abnormalities, liver cirrhosis.
• Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg).
• Known cardiac arrhythmia, including if asymptomatic or previous history of arrhythmia.
• Heart rate ≥ 100 beats/minute at screening on two separate measurements.

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

University College London

London, United Kingdom

Location

MeSH Terms

Conditions

Obesity; Appetitive Behavior

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior, Animal; Behavior

Study Officials

• Rachel L Batterham, PhD FRCP

  UCL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double blind, placebo-controlled, within-subject, crossover mechanistic study

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: August 22, 2018
• Study Start: February 15, 2019
• Primary Completion: March 6, 2020
• Study Completion: March 13, 2020
• Last Updated: May 20, 2020

Record last verified: 2020-05

Locations

GB (1)