ObesityEarly Phase 1GHADDNCT02690987
Gut Hormones in Obesity, Nicotine and Alcohol Dependence
A Early Phase 1 study testing Exenatide, Desacyl ghrelin and Saline in people with Obesity and Smoking Cessation, run by Imperial College London at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Smoking Cessation, Alcoholism
- What is being tested?
- Exenatide, Desacyl ghrelin and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2015to Aug 2020
- Phase
- Early Phase 1
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female volunteers between the ages of 18 and 60 years.
- Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests, cardiac monitoring and a psychiatric evaluation. Any volunteer with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included, only if the investigators concur that the finding is unlikely to jeopardize either volunteer safety or study integrity.
- The subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- The subject is able to read, comprehend and record information written in English.
- For non-dependent groups:
- Overweight/obese volunteers with BMI 28.0-50.0 kg/m2.
Show all 10Show fewer
- For addiction groups:
- Subjects meeting Diagnostic and Statistical Manual (DSM)-V criteria for previous nicotine or alcohol dependence, but who are in early stable abstinence (>6 weeks). Minor lapses within this time period will be allowed but not relapses into dependence.
- Abstinent alcohol dependent individuals who score at least moderately alcohol dependent as measured retrospectively using the Severity of Alcohol Dependence Questionnaire (SADQ), and who have been abstinent for >6 weeks.
- Abstinent tobacco dependent individuals who score at least moderately on tobacco dependence as measured retrospectively using the Fagerström Test for Nicotine Dependence (FTND), and who have been in stable tobacco abstinence for >6 weeks.
Who cannot join
- Potential volunteers will NOT be eligible for inclusion in this study if any of the following criteria apply:
- Previous history of recreational use or abuse of other substances of addiction will be permissible, but there should be no use of any illegal drugs (except cannabis) in the month prior to the Screening Visit or during the course of the study, except where specified for individual groups below.
- For individual groups:
- Overweight/obese group: history of or current alcohol abuse or dependence; nicotine use other than "never smoked", i.e. >100 cigarettes lifetime use; history of dependence, abuse or heavy recreational use of cocaine, cannabis, opiates or other substance of abuse; history of problem gambling. Any previous or current psychiatric diagnosis listed in Diagnostic and Statistical Manual (DSM)-V Axis I, which in the opinion of the clinical team will compromise conduct and interpretability of the study.
- Abstinent tobacco dependent group: history of or current alcohol abuse or dependence; current dependence for cocaine, cannabis, opiates or other substance of abuse, or problem gambling (previous history will be allowed); taking varenicline, bupropion or other prescription medications for smoking cessation. Any previous or current psychiatric diagnosis listed in Diagnostic and Statistical Manual (DSM)-V Axis I, which in the opinion of the clinical team will compromise conduct and interpretability of the study.
- Abstinent alcohol dependent group: current dependence for cocaine, cannabis, opiates or other substance of abuse, or problem gambling (previous history will be allowed); taking prescription medication for alcohol or smoking cessation or withdrawal; smoking is allowed past or present including dependence; current nicotine replacement therapy is allowed.
Show all 35Show fewer
- Currently suffering from Diagnostic and Statistical Manual (DSM)-V depressive disorder or on anti-depressant medication, though a history of depression or anxiety will be allowed. A current or past history of enduring severe mental illness (e.g., schizophrenia, bipolar affective disorder) will not be allowed.
- For all groups:
- Cannabis use up to five times in the month prior to the Screening Visit will be allowed, but no use within one week of experimental assessments; no use of any other illegal drugs in the month prior to the Screening Visit or during the course of the study.
- Intoxication at any of the visits, as manifested by difficulty in walking, slurring of speech, difficulty concentrating or drowsiness (or by the subject volunteering this information directly to the research team).
- Positive drug/alcohol screens on testing at the screening visit, other than that explicable by other causes (e.g. recent use of opiate containing analgesic etc), at the discretion of the research team.
- Carbon monoxide levels of =/>10ppm in the overweight/obese and abstinent smoker groups at screening visit.
- Use of current regular prescriptions (including smoking or alcohol cessation medicines such as Disulfiram, Acamprosate, Naltrexone, Bupropion; weight loss medication including Orlistat, Metformin, GLP-1 agonists, Bupropion, Naltrexone), or over-the-counter medications that in the opinion of the Investigators may affect subject safety or outcome measures.
- Pulse rate <40 or >100 beats per minute OR systolic blood pressure >160 and <100 and a diastolic blood pressure >95 and <50 in the semi-supine position.
- Claustrophobia or feels that they will be unable to lay still on their back in the MRI scanner for a period of ~80 minutes.
- Presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies as assessed by a standard pre-MRI questionnaire and radiographer.
- History or presence of a neurological diagnosis (not limited to but including, for example, stroke, epilepsy, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischemic attack, that may influence the outcome or analysis of the scan results). A history of alcohol-related or alcohol-withdrawal seizures will be allowed for volunteers in the abstinent alcoholic group.
- Significant current or past medical or psychiatric history that, in the opinion of the investigators, contraindicates their participation.
- Clinically significant head injury (e.g. requiring hospitalisation or surgical intervention) that in the opinion of the investigators may affect subject safety or outcome measures.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Any of the following liver function tests (LFT) abnormalities at screening: Alkaline Phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or gammaGT > 4 x upper limit of normal (ULN), International Normalised ratio (INR) > 1.5, Albumin <25 g/L, raised bilirubin (other than just isolated i.e. without other liver function tests abnormalities).
- History of decompensated alcoholic liver disease - i.e. history of variceal bleeding, ascites, jaundice, encephalopathy.
- History of pancreatitis from any cause.
- History of type 1 or type 2 diabetes mellitus.
- ECG abnormality, which in the opinion of the study physician, is clinically significant and represents a safety risk.
- The volunteer has participated in a clinical trial and has received an investigational product within the following time period prior to the first experimental visit in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than 3 new investigational medicinal products within 12 months prior to the scan.
- History of sensitivity to any of the peptides, or components thereof, or a history of drug or other allergy that, in the opinion of the investigators, contraindicates their participation.
- Diagnosis of endocrine disorder, including uncontrolled hypothyroidism (stable treated hypothyroidism with currently normal thyroid function tests is allowed), history of hyperthyroidism or Cushing's syndrome, which, in the opinion of the investigators, may affect subject safety or outcome measures.
- History of ischaemic heart disease, heart failure, cardiac arrhythmia or peripheral vascular or cerebrovascular disease.
- History or presence of significant respiratory, gastrointestinal, hepatic, oncological or renal disease or other condition that in the opinion of the Investigators may affect subject safety or outcome measures.
- Previous bariatric surgery for obesity including Roux-en-Y gastric bypass, gastric banding, sleeve gastrectomy.
- Current pregnancy or breast-feeding in female volunteers.
- Vegetarian, vegan, gluten or lactose-intolerant.
- Volunteers who have donated, or intend to donate, blood within three months before the screening visit or following study visit completion.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, Hammersmith Hospital
London, W12 0NN
About this study
Official title: Do Appetitive Gut Hormones Reduce Addictive and Eating Behaviours in Obesity, and Nicotine and Alcohol Dependence?
The "Gut Hormones in Addiction" study is a proof-of-concept experimental medicine human study to answer the following questions:
- 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?
- 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?
- 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?
Read the 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
- Being tested
- Exenatide, Desacyl ghrelin, Saline
- Keywords
- tobacco, GLP1, ghrelin, alcohol, appetite, reward, addiction, hormone, cigarette, functional MRI
- Medical subject headings
- Obesity, Smoking Cessation, Alcoholism, Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExenatideDrug
Also called Byetta
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.
Desacyl ghrelinBiological
Also called Unacylated 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.
SalineBiological
The placebo visit will involve an intravenous infusion of normal saline.
| Study group | Role | What they receive |
|---|---|---|
| Overweight/obese subjects | Experimental | Overweight/obese volunteers with BMI 28.0-50.0 kg/m2, otherwise healthy. This group will receive interventions with saline as placebo, Exenatide and desacyl ghrelin infusions at separate visits in a within subject randomised crossover design. Receives: Drug: Exenatide; Biological: Desacyl ghrelin; Biological: Saline |
| Ex-smokers | Experimental | Abstinent tobacco dependent individuals who score at least moderately on tobacco dependence as measured retrospectively using the Fagerström Test for Nicotine Dependence (FTND), and who have been in stable tobacco abstinence for at least 6 weeks.
This group will receive interventions with saline as placebo, Exenatide and desacyl ghrelin infusions at separate visits in a within subject randomised crossover design. Receives: Drug: Exenatide; Biological: Desacyl ghrelin; Biological: Saline |
| Ex-alcohol dependent subjects | Experimental | Abstinent alcohol dependent individuals who score at least moderately alcohol dependent as measured retrospectively using the Severity of Alcohol Dependence Questionnaire (SADQ), and who have been abstinent for at least 6 weeks.
This group will receive interventions with saline as placebo, Exenatide and desacyl ghrelin infusions at separate visits in a within subject randomised crossover design. Receives: Drug: Exenatide; Biological: Desacyl ghrelin; Biological: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional MRI measure of brain activation during cigarette, alcohol and food picture evaluation task
Blood oxygen level dependent (BOLD) signal in brain reward systems to cigarette, alcohol and food pictures vs. object pictures
Measured: 4 years
Secondary outcomes (5)
Functional MRI measure of brain activation during anticipation of winning monetary reward (monetary incentive delay task)
Blood oxygen level dependent (BOLD) signal in striatum to anticipation of winning vs. not winning money
Measured: 4 years
Functional MRI measure of brain activation during negative emotional reactivity task
Blood oxygen level dependent (BOLD) signal in amygdala during viewing of evocative vs. neutral pictures
Measured: 4 years
Functional MRI measure of brain activity in salience resting state network
Network integrity of blood oxygen level dependent (BOLD) signal in salience resting state network
Measured: 4 years
Functional MRI measure of brain activity in limbic resting state network
Network integrity of blood oxygen level dependent (BOLD) signal in limbic resting state network
Measured: 4 years
Functional MRI measure of brain activity in default mode resting state network
Network integrity of blood oxygen level dependent (BOLD) signal in default mode resting state network
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2016 (estimated)
- Study startAug 2015
- Primary completion21 Aug 2019
- Study completionAug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Imperial 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 95 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tony Goldstone, MD, PhD, Principal investigator, Imperial College LondonDavid Nutt, MD, PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02690987
- Sponsor's protocol ID
- 15/LO/1041
- Other IDs
- MR/M007022/1
- Acronym
- GHADD
- Status last verified
- Feb 2020
- First submitted
- 11 Nov 2015
- Last updated
- 13 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dickson SL, Egecioglu E, Landgren S, Skibicka KP, Engel JA, Jerlhag E. The role of the central ghrelin system in reward from food and chemical drugs. Mol Cell Endocrinol. 2011 Jun 20;340(1):80-7. doi: 10.1016/j.mce.2011.02.017. Epub 2011 Feb 24.
PubMed 21354264Egecioglu E, Engel JA, Jerlhag E. The glucagon-like peptide 1 analogue Exendin-4 attenuates the nicotine-induced locomotor stimulation, accumbal dopamine release, conditioned place preference as well as the expression of locomotor sensitization in mice. PLoS One. 2013 Oct 18;8(10):e77284. doi: 10.1371/journal.pone.0077284. eCollection 2013.
PubMed 24204788Goldstone AP, Prechtl CG, Scholtz S, Miras AD, Chhina N, Durighel G, Deliran SS, Beckmann C, Ghatei MA, Ashby DR, Waldman AD, Gaylinn BD, Thorner MO, Frost GS, Bloom SR, Bell JD. Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food. Am J Clin Nutr. 2014 Jun;99(6):1319-30. doi: 10.3945/ajcn.113.075291. Epub 2014 Apr 23.
PubMed 24760977Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO. The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict. 1991 Sep;86(9):1119-27. doi: 10.1111/j.1360-0443.1991.tb01879.x.
PubMed 1932883Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption--II. Addiction. 1993 Jun;88(6):791-804. doi: 10.1111/j.1360-0443.1993.tb02093.x.
PubMed 8329970Shirazi RH, Dickson SL, Skibicka KP. Gut peptide GLP-1 and its analogue, Exendin-4, decrease alcohol intake and reward. PLoS One. 2013 Apr 16;8(4):e61965. doi: 10.1371/journal.pone.0061965. Print 2013.
PubMed 23613987Tong J, Davis HW, Summer S, Benoit SC, Haque A, Bidlingmaier M, Tschop MH, D'Alessio D. Acute administration of unacylated ghrelin has no effect on Basal or stimulated insulin secretion in healthy humans. Diabetes. 2014 Jul;63(7):2309-19. doi: 10.2337/db13-1598. Epub 2014 Feb 18.
PubMed 24550190van Bloemendaal L, IJzerman RG, Ten Kulve JS, Barkhof F, Konrad RJ, Drent ML, Veltman DJ, Diamant M. GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans. Diabetes. 2014 Dec;63(12):4186-96. doi: 10.2337/db14-0849. Epub 2014 Jul 28.
PubMed 25071023Scholtz S, Miras AD, Chhina N, Prechtl CG, Sleeth ML, Daud NM, Ismail NA, Durighel G, Ahmed AR, Olbers T, Vincent RP, Alaghband-Zadeh J, Ghatei MA, Waldman AD, Frost GS, Bell JD, le Roux CW, Goldstone AP. Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding. Gut. 2014 Jun;63(6):891-902. doi: 10.1136/gutjnl-2013-305008. Epub 2013 Aug 20.
PubMed 23964100
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Do Appetitive Gut Hormones Reduce Addictive and Eating Behaviours in Obesity, and Nicotine and Alcohol Dependence?
- ClinicalTrials.gov ID
- NCT02690987
- Acronym / sponsor ID
- GHADD / 15/LO/1041
- Conditions
- Obesity, Smoking Cessation, Alcoholism
- Keywords
- tobacco, GLP1, ghrelin, alcohol, appetite, reward, addiction, hormone
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Aug 2015 (actual)
- Primary completion
- 21 Aug 2019 (actual)
- Study completion
- Aug 2020 (estimated)
- First posted
- 24 Feb 2016 (estimated)
- 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.
The "Gut Hormones in Addiction" study is a proof-of-concept experimental medicine human study to answer the following questions:
- 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?
- 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?
- 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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Overweight/obese subjects | Experimental | Drug: Exenatide, Biological: Desacyl ghrelin, Biological: SalineOverweight/obese volunteers with BMI 28.0-50.0 kg/m2, otherwise healthy. This group will receive interventions with saline as placebo, Exenatide and desacyl ghrelin infusions at separate visits in a within subject randomised crossover design. |
| Ex-smokers | Experimental | Drug: Exenatide, Biological: Desacyl ghrelin, Biological: SalineAbstinent tobacco dependent individuals who score at least moderately on tobacco dependence as measured retrospectively using the Fagerström Test for Nicotine Dependence (FTND), and who have been in stable tobacco abstinence for at least 6 weeks. This group will receive interventions with saline as placebo, Exenatide and desacyl ghrelin infusions at separate visits in a within subject randomised crossover design. |
| Ex-alcohol dependent subjects | Experimental | Drug: Exenatide, Biological: Desacyl ghrelin, Biological: SalineAbstinent alcohol dependent individuals who score at least moderately alcohol dependent as measured retrospectively using the Severity of Alcohol Dependence Questionnaire (SADQ), and who have been abstinent for at least 6 weeks. This group will receive interventions with saline as placebo, Exenatide and desacyl ghrelin infusions at separate visits in a within subject randomised crossover design. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Male or female volunteers between the ages of 18 and 60 years.
- Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests, cardiac monitoring and a psychiatric evaluation. Any volunteer with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included, only if the investigators concur that the finding is unlikely to jeopardize either volunteer safety or study integrity.
- The subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- The subject is able to read, comprehend and record information written in English.
- For non-dependent groups:
Key exclusion criteria (35 listed)
- Potential volunteers will NOT be eligible for inclusion in this study if any of the following criteria apply:
- Previous history of recreational use or abuse of other substances of addiction will be permissible, but there should be no use of any illegal drugs (except cannabis) in the month prior to the Screening Visit or during the course of the study, except where specified for individual groups below.
- For individual groups:
- Currently suffering from Diagnostic and Statistical Manual (DSM)-V depressive disorder or on anti-depressant medication, though a history of depression or anxiety will be allowed. A current or past history of enduring severe mental illness (e.g., schizophrenia, bipolar affective disorder) will not be allowed.
- Cannabis use up to five times in the month prior to the Screening Visit will be allowed, but no use within one week of experimental assessments; no use of any other illegal drugs in the month prior to the Screening Visit or during the course of the study.
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 |
|---|---|---|
| ExenatideAlso: ByettaExenatide 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. | Drug | Ex-alcohol dependent subjects, Ex-smokers, Overweight/obese subjects |
| Desacyl ghrelinAlso: Unacylated ghrelinGhrelin 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 | Ex-alcohol dependent subjects, Ex-smokers, Overweight/obese subjects |
| SalineThe placebo visit will involve an intravenous infusion of normal saline. | Biological | Ex-alcohol dependent subjects, Ex-smokers, Overweight/obese subjects |
Primary outcome
Functional MRI measure of brain activation during cigarette, alcohol and food picture evaluation task
Time frame: 4 years
Blood oxygen level dependent (BOLD) signal in brain reward systems to cigarette, alcohol and food pictures vs. object pictures
5 secondary outcomes
Functional MRI measure of brain activation during anticipation of winning monetary reward (monetary incentive delay task)
Time frame: 4 years
Functional MRI measure of brain activation during negative emotional reactivity task
Time frame: 4 years
Functional MRI measure of brain activity in salience resting state network
Time frame: 4 years
Functional MRI measure of brain activity in limbic resting state network
Time frame: 4 years
Functional MRI measure of brain activity in default mode resting state network
Time frame: 4 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2020.
- Background: PubMed 21354264Dickson SL, Egecioglu E, Landgren S, Skibicka KP, Engel JA, Jerlhag E. The role of the central ghrelin system in reward from food and chemical drugs. Mol Cell Endocrinol. 2011 Jun 20;340(1):80-7. doi: 10.1016/j.mce.2011.02.017. Epub 2011 Feb 24.
- Background: PubMed 24204788Egecioglu E, Engel JA, Jerlhag E. The glucagon-like peptide 1 analogue Exendin-4 attenuates the nicotine-induced locomotor stimulation, accumbal dopamine release, conditioned place preference as well as the expression of locomotor sensitization in mice. PLoS One. 2013 Oct 18;8(10):e77284. doi: 10.1371/journal.pone.0077284. eCollection 2013.
- Background: PubMed 24760977Goldstone AP, Prechtl CG, Scholtz S, Miras AD, Chhina N, Durighel G, Deliran SS, Beckmann C, Ghatei MA, Ashby DR, Waldman AD, Gaylinn BD, Thorner MO, Frost GS, Bloom SR, Bell JD. Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food. Am J Clin Nutr. 2014 Jun;99(6):1319-30. doi: 10.3945/ajcn.113.075291. Epub 2014 Apr 23.
- Background: PubMed 1932883Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO. The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict. 1991 Sep;86(9):1119-27. doi: 10.1111/j.1360-0443.1991.tb01879.x.
- Background: PubMed 8329970Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption--II. Addiction. 1993 Jun;88(6):791-804. doi: 10.1111/j.1360-0443.1993.tb02093.x.
- Background: PubMed 23613987Shirazi RH, Dickson SL, Skibicka KP. Gut peptide GLP-1 and its analogue, Exendin-4, decrease alcohol intake and reward. PLoS One. 2013 Apr 16;8(4):e61965. doi: 10.1371/journal.pone.0061965. Print 2013.
- Background: PubMed 24550190Tong J, Davis HW, Summer S, Benoit SC, Haque A, Bidlingmaier M, Tschop MH, D'Alessio D. Acute administration of unacylated ghrelin has no effect on Basal or stimulated insulin secretion in healthy humans. Diabetes. 2014 Jul;63(7):2309-19. doi: 10.2337/db13-1598. Epub 2014 Feb 18.
- Background: PubMed 25071023van Bloemendaal L, IJzerman RG, Ten Kulve JS, Barkhof F, Konrad RJ, Drent ML, Veltman DJ, Diamant M. GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans. Diabetes. 2014 Dec;63(12):4186-96. doi: 10.2337/db14-0849. Epub 2014 Jul 28.
- Background: PubMed 23964100Scholtz S, Miras AD, Chhina N, Prechtl CG, Sleeth ML, Daud NM, Ismail NA, Durighel G, Ahmed AR, Olbers T, Vincent RP, Alaghband-Zadeh J, Ghatei MA, Waldman AD, Frost GS, Bell JD, le Roux CW, Goldstone AP. Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding. Gut. 2014 Jun;63(6):891-902. doi: 10.1136/gutjnl-2013-305008. Epub 2013 Aug 20.
- GHADD study websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Tony Goldstone, MD, PhD principal investigator
Imperial College London
David Nutt, MD, PhD principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Exenatide, Desacyl ghrelin and Saline in people with Obesity and Smoking Cessation, run by Imperial 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 35 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: status not confirmed, as of the sponsor's last update on 13 Feb 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Functional MRI measure of brain activation during cigarette, alcohol and food picture evaluation task (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02690987, which also lists 9 linked publications.
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 13 Feb 2020.