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Gut hormone LEAP2 in metabolism and eating behaviour

About the study

Obesity is a major health burden, with significant economic and societal impacts. After people lose weight, it is common for them to regain it over time. This is driven in part by hormones from the gut and fat cells in the body which act on the brain to influence eating behaviour. One such hormone is ghrelin, which stimulates appetite, food intake and acts on the hunger and reward circuits in the brain. It increases in the blood when people fast or lose weight, and falls when they eat food or gain weight.

A new hormone called liver-expressed antimicrobial peptide 2 (LEAP2) was recently discovered, which is produced by the gut, and in animal studies blocks the action of ghrelin at its receptor. Blood levels of LEAP2 move in the opposite direction to ghrelin and may therefore be a potential treatment to help people lose weight initially or particularly to maintain their weight loss.

Our study, funded by the UK Medical Research Council, entitled 'Gut hormone LEAP2 in metabolism and eating behaviour', will take the Hammersmith Hospital, at Imperial College London. The LEAP2 study has been ethically approved by the West London & GATC Research Ethics Committee (REC no. 23/LO/510, IRAS 304210).

We are recruiting volunteers for our study including using brain scanning to investigate the effects of such gut hormones on eating and addictive behaviours. This could give us important information about how the LEAP2 has the additional benefits of preventing weight gain. Therefore, this will recognise if targeting LEAP2 will help develop new medicines to treat obesity.

You will receive payment for your time and reasonable travel expenses if you take part in the LEAP2 study. The LEAP2 hormone research is further subdivided into 3 different studies:

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Study 1 (Fixed meal testing)

The aim of Study 1 (Fixed meal testing) is to examine the effects of different meals on plasma concentrations of LEAP2 and other hormones, and its relationship with appetite in participants with and without obesity. If eligible, you would have an initial health screening visit, and then up to five study visits over 3-8 weeks, each lasting up to 4.5 hours in the morning depending on your availability. At the study visits, you will be given liquid meals of different sizes and content in a randomised order, will have blood samples taken and tests of appetite and eating behaviour including questionnaires. You will be paid for your time.

Study 2 (Dose confirmation)

The aim of Study 2 (Dose confirmation) is to administer LEAP2 hormone through a vein over several hours (vs. placebo water infusion) to healthy participants without obesity. This is to confirm what blood levels of LEAP2 are achieved with different infusion doses, and what dose is needed to give to achieve slightly higher than those normally seen in the blood. We will be assessing changes in appetite and amount of food eaten, influence on blood levels of other hormones, and ensuring that doses given are safe and do not cause any side effects of concern. If eligible, you would have an initial screening visit, and then up to six study visits over 4-10 weeks, each lasting up to 8 hours from the morning depending on your availability. At the study visits, you will have blood samples taken, and tests of eating behaviour, including questionnaires, computer-based cognitive tasks, and a test meal during the infusion. Infusion doses will be different at each visit, with progression to higher doses based on tolerability, safety and serial plasma LEAP2 concentrations. You will be paid expenses including travel costs.

Study 3 (Functional MRI)

The aim of Study 3 (Neuroimaging and eating behavioural mechanisms) is to evaluate the effect of administration of LEAP2 hormone (vs. placebo water infusion) on appetite, eating and addictive behaviours, metabolism and other hormones in participants without obesity. We will investigate the effects of LEAP2 while you undergo an MRI scan, to see if it reduces brain activation when shown pictures of food, alcohol or stressful images, or play a game where points can be won towards money, food or alcohol rewards. If eligible, you would have an initial screening visit, and then four study visits over 4-8 weeks, each lasting up to 8 hours from the morning depending on your availability. At the study visits, you will have blood samples taken, and tests of eating behaviour, including questionnaires, computer-based cognitive tasks, and an MRI brain scan during the infusion. You will be paid expenses including travel costs.

What is involved?

If you are interested in taking part, you will be directed to the online screening questionnaire and we would then contact you by phone for a telephone screening to confirm you are eligible and let you know more about the study. You would then need to come for an initial morning screening visit, followed by additional study visits. All visits will take place at the NIHR Imperial Clinical Research Facility and the Clinical Imaging Facility, at the Hammersmith Hospital (near White City, London W12 0NN).

To be eligible to take part, you need to be:

  • Either male or female
  • 18-60 years of age
  • Without obesity (BMI <30kg/m; for studies 1, 2 and 3)
  • With obesity (BMI >30kg/m2; only for study 1)
  • Stable weight (no change to weight of more than 5% over the last 3 months)
  • You must NOT have had
    • a stroke
    • a heart attack
    • diabetes
    • a heart pacemaker or any other metallic implants (only for Study 3)
    • You must NOT be claustrophobic (only for Study 3)
  • You must NOT be vegetarian, vegan, or gluten- or lactose-intolerant
  • Be able to read, speak and understand spoken and written English
  • Be willing to complete multiple separate visits to the Hammersmith Hospital over approximately 4-10 weeks

How do I find out more?

Please click on the relevant survey links below so that we can see if you may be eligible to take part. If so, you will be given the opportunity to leave your contact details, so that we can discuss the study with you.

Please note that you can only take part in one of the three studies.

Alternatively, if would like to learn more about the study and are happy for us to contact you, please email the study team at appetite@imperial.ac.uk or by phone on 020 7594 5988.

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Contact us


LEAP2 Study Team
PsychoNeuroEndocrinology Research Group
Department of Brain Sciences
Imperial College London
Commonwealth Building
Hammersmith Hospital
Du Cane Road
London W12 0NN 

Email: appetite@imperial.ac.uk
Tel: 020 7594 5988

Study team


Principal Investigator: Dr Tony Goldstone

Co-Investigators: Dr Raghav Bhargava, Dr Marcela Rodriguez Flores, Ms Sandra Luur