ObesityBARI-INSIGHTNCT03641417
Investigating the Role of Ghrelin in Regulating Appetite and Energy Intake in Patients Following Bariatric Surgery (BARI-INSIGHT)
A study testing GLWL-01 in people with Obesity and Bariatric Surgery Candidate, run by University College, London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Obesity, Bariatric Surgery Candidate, Appetitive Behavior
- What is being tested?
- GLWL-01
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 15 Feb 2019to 13 Mar 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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
- 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.
- History of stroke, unstable angina, acute coronary syndrome, congestive heart failure New York Heart Association class III-IV within the preceding 12 months.
- Have an abnormality in the 12-lead ECG, including corrected QT interval with Frederica's correction (QTcF) >450 msec for men and >470 msec for women or an abnormality that, in the opinion of the investigator, increases the risks associated with participating in the study. If QTcF does not meet criteria, ECGs may be repeated once after 5 minutes of rest.
- Renal impairment (estimated glomerular infiltration rate eGFR <60 ml/min 1.73 m2)
- History or evidence of liver disease
- Chronic disease: including but not limited to chronic alcoholic liver disease, cirrhosis of any cause or chronic autoimmune hepatitis.
- Acute disease: recent history (within 3 months of screening) of acute viral hepatitis
- Liver function test values (AST, ALT, GGT, ALP) > 3x the upper normal limit
- History of biliary disease including primary sclerosing cholangitis.
- Patients with a history of cholecystectomy more than 6 months prior to screening are eligible for recruitment.
- History of pancreatitis.
- Evidence of human immunodeficiency virus (HIV) infection, hepatitis B, hepatitis C and/or positive results at screening for the respective antibodies for HIV, hepatitis B surface antigen, or hepatitis C antibodies.
- Evidence of significant active or unstable/uncontrolled psychiatric disease by medical history.
- Lifetime history of suicidal behaviour or severe depression assessed by direct questioning and review of medical history.
- Patients whose disease state is considered stable and expected to remain stable throughout the course of the study, in the opinion of the investigator, may be considered for inclusion if they are not on excluded medications.
- Use of weight loss medications within 30 days of first dose of study medication.
- Concomitant usage of GLP-1 receptor agonist/DPPIV-inhibitors/insulin.
- Unable to refrain from or anticipates the use of:
- Any drugs known to be significant inhibitors of cytochrome P450 (CYP)3A enzymes and/or P-glycoprotein (P-gp) including regular consumption of grapefruit or grapefruit juice for 14 days prior to the first dose of study medication and throughout the study. Appropriate sources will be consulted by the principal investigator (PI) or designee to confirm lack of pharmacokinetic (PK) or pharmacodynamic (PD) interaction with study medication. Paracetamol (up to 2 grams per 24-hour period) may be permitted during the study.
- Any drugs known to be significant inducers of CYP3A enzymes and/or P-gp, including St. John's Wort, for 28 days prior to the first dose of study medication and throughout the study. Appropriate sources will be consulted by the PI or designee to confirm lack of PK/PD interaction with study medication.
- Currently taking simvastatin >10 mg per day, atorvastatin >20 mg per day, or lovastatin >20 mg per day. The doses of these statins in combination products should not exceed these defined dose levels. Patients with a history of statin-induced myopathy/rhabdomyolysis should also be excluded.
- Regular user of known drugs of abuse and/or shows positive findings on urinary drug screening.
- An average weekly alcohol intake that exceeds 21 units per week (males ≤65 years of age) and 14 units per week (females and males >65 years of age), or is unwilling to stop alcohol consumption for the duration of the study (1 unit = 360 mL of beer; 150 mL of wine; 45 mL of distilled spirits).
- Venous access insufficient to allow for blood sampling as per the protocol.
- Any major surgery within 60 days prior to the first dose or has planned elective surgeries to occur during the study.
- Unsuitable for inclusion in the study in the opinion of the investigator.
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- GLWL-01, Placebo
- Keywords
- Obesity, Bariatric surgery, Appetite, Ghrelin, Energy intake, Gut hormones, Adipokines
- Medical subject headings
- Obesity, Appetitive Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GLWL-01Drug
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.)
PlaceboOther
Same as GLWL-01, but no active ingredient
| Study group | Role | What they receive |
|---|---|---|
| GLWL-01 | Experimental | Oral administration of GLWL-01 300mg BD for 10 days Receives: Drug: GLWL-01 |
| Placebo | Placebo comparator | Identical oral capsules with no active ingredient, administered BD for 10 days Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Within-subject acute energy intake
Evaluate the effect of reduced circulating AG on within-subject acute energy intake assessed during an ad libitum meal.
Measured: Final day of each study cycle, Day 10
Secondary outcomes (10)
Fasted appetite scores
in response to a fixed meal assessed using visual analogue scales (VAS).
Measured: Day 7 of each study cycle
Area-under-the-curve for appetite scores
in response to a fixed meal assessed using visual analogue scales (VAS).
Measured: Day 7 of each study cycle
Macronutrient selection
assessed using a 24-hour diet diary and food selection during the ad libitum meal.
Measured: Daily during each study cycle
Subjective aspects of appetite
specifically hunger, fullness, pleasantness to eat and nausea. Assessed using VAS and food craving questionnaires.
Measured: Final day of each study cycle, Day 10
24-hour energy intake
assessed using a 24-hour diet diary, completed daily during GLWL-01 and placebo study arms.
Measured: Final day of each study cycle, Day 10
Gut hormones levels
Circulating levels of gut hormones in response to a fixed meal.
Measured: Day 7 of each study cycle
Adipokine levels
Circulating levels of adipokines in response to a fixed meal
Measured: Day 7 of each study cycle
Body weight
assessed using a bioelectrical impedance analyser (BIA).
Measured: Final day of each study cycle, Day 10
Body composition
assessed using a bioelectrical impedance analyser (BIA).
Measured: Final day of each study cycle, Day 10
Inflammatory markers and cytokines
Evaluate the effect of reduced circulating AG on circulating inflammatory markers and cytokines.
Measured: Final day of each study cycle, Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2018
- Study start15 Feb 2019
- Primary completion6 Mar 2020
- Study completion13 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double blind, placebo-controlled, within-subject, crossover mechanistic study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rachel L Batterham, PhD FRCP, Principal investigator, UCL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03641417
- Sponsor's protocol ID
- 17/0887
- Acronym
- BARI-INSIGHT
- Status last verified
- May 2020
- First submitted
- 1 Aug 2018
- Last updated
- 20 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03641417
- Acronym / sponsor ID
- BARI-INSIGHT / 17/0887
- Conditions
- Obesity, Bariatric Surgery Candidate, Appetitive Behavior
- Keywords
- Obesity, Bariatric surgery, Appetite, Ghrelin, Energy intake, Gut hormones, Adipokines
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- 15 Feb 2019 (actual)
- Primary completion
- 6 Mar 2020 (actual)
- Study completion
- 13 Mar 2020 (actual)
- First posted
- 22 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Double blind, placebo-controlled, within-subject, crossover mechanistic study
| Arm | Type | Receives |
|---|---|---|
| GLWL-01 | Experimental | Drug: GLWL-01Oral administration of GLWL-01 300mg BD for 10 days |
| Placebo | Placebo comparator | Other: PlaceboIdentical oral capsules with no active ingredient, administered BD for 10 days |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (40 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GLWL-01Small 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.) | Drug | GLWL-01 |
| PlaceboSame as GLWL-01, but no active ingredient | Other | Placebo |
Primary outcome
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.
10 secondary outcomes
Fasted appetite scores
Time frame: Day 7 of each study cycle
Area-under-the-curve for appetite scores
Time frame: Day 7 of each study cycle
Macronutrient selection
Time frame: Daily during each study cycle
Subjective aspects of appetite
Time frame: Final day of each study cycle, Day 10
24-hour energy intake
Time frame: Final day of each study cycle, Day 10
Gut hormones levels
Time frame: Day 7 of each study cycle
Adipokine levels
Time frame: Day 7 of each study cycle
Body weight
Time frame: Final day of each study cycle, Day 10
Body composition
Time frame: Final day of each study cycle, Day 10
Inflammatory markers and cytokines
Time frame: Final day of each study cycle, Day 10
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachel L Batterham, PhD FRCP principal investigator
UCL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GLWL-01 in people with Obesity and Bariatric Surgery Candidate, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Within-subject acute energy intake (time frame: Final day of each study cycle, Day 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2020.