NCT02690987

Gut Hormones in Obesity, Nicotine and Alcohol Dependence

Do Appetitive Gut Hormones Reduce Addictive and Eating Behaviours in Obesity, and Nicotine and Alcohol Dependence?

• Status: Unknown
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 95 (actual)
• Sponsor: Imperial College London · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

The "Gut Hormones in Addiction" study is a proof-of-concept experimental medicine human study to answer the following questions: 1. Does the administration of the hormone desacyl ghrelin reduce core behavioural components of addiction in dependent individuals who have recently stopped smoking tobacco or drinking alcohol, or overweight/obese subjects? 2. Does the administration of the drug Exenatide reduce core behavioural components of addiction in dependent individuals who have recently stopped smoking tobacco or drinking alcohol, or overweight/obese subjects? 3. Does the administration of desacyl ghrelin or Exenatide reduce reward responses to high-calorie foods and appetite in dependent individuals who have recently stopped smoking tobacco or drinking alcohol, or overweight/obese subjects?

Detailed description

Obesity, smoking and alcohol dependence are major health burdens to society. Relapse after alcohol and smoking abstinence is common despite the use of combined behavioural support and current limited available medications. In obesity, nonsurgical interventions have also been disappointing in achieving longterm weight loss. Therefore, there is a pressing need to develop novel drug treatments for addiction derived from knowledge of brain mechanisms related to relapse and reward responses to food and drugs. There is evidence in animals that some gut hormones, produced in the stomach and intestine, influence the consumption of food and desire for food, but also alcohol, nicotine and other drugs of abuse. Examples of such gut hormones are glucagon-like peptide1 (GLP1) and ghrelin. The influence of these hormones is exerted through brain systems involved in the core behavioural components of addiction: reward sensitivity, stress, impulsivity and compulsivity. These components are often also seen in obesity and food-related disorders such as binge eating disorder. It is unknown whether these gut hormones directly influence the core behavioural components of addiction in humans, particularly during abstinence. The investigators will examine the acute effects of Exenatide (mimics GLP1) and desacyl ghrelin (counteracts active acyl ghrelin), which are infused through a vein, on brain reward systems, craving for food, cigarettes and alcohol, and addictive and eating behaviours. The investigators will recruit adults with nicotine or alcohol dependence who have recently stopped smoking or drinking, and overweight/obese adults. The investigators will use functional magnetic resonance imaging (MRI) brain scans and computer-based test over 3 separate study days to study different aspects of eating and addictive behaviours.

Conditions

• Obesity
• Smoking Cessation
• Alcoholism

Interventions

Type	Name	Description
DRUG	Exenatide	Exenatide is a commercially available GLP-1 receptor agonist. It is a synthetic form of exendin-4, a protein extracted from the saliva of a Gila monster lizard, which exhibits 53% sequence identity to human GLP-1. The planned intravenous Exenatide infusion dose is expected to be 0.06 pmol/kg/min aiming for maintenance plasma concentrations of \~130-190 pg/mL.
BIOLOGICAL	Desacyl ghrelin	Ghrelin is a 28 amino acid stomach-derived peptide hormone, with the desacyl ghrelin (DAG) form inactive at the GHSR1a receptor. Good Manufacturing Practice (GMP)-grade DAG is obtained from Clinalfa (Bachem AG, Bubendorf, Switzerland). The planned intravenous DAG infusion dose is expected to be 4.0 mcg/kg/hour aiming for maintenance plasma concentrations of \~13-19 ng/mL.
BIOLOGICAL	Saline	The placebo visit will involve an intravenous infusion of normal saline.

Timeline

• Start date: 2015-08-01
• Primary completion: 2019-08-21
• Completion: 2020-08-01
• First posted: 2016-02-24
• Last updated: 2020-02-13

Locations

1 site across 1 country: United Kingdom