APPETITE: linguAl PYY3-36 on aPpEtite and acuTe Energy InTakE

Study Overview
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Brief Summary
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A double-blind, cross-over, placebo-controlled, proof-of-concept study using oral peptide YY3-36 solution to investigate the mechanistic role of lingual PYY in regulating appetite, energy intake and food preference in people with overweight/obesity. The aim of this study is to investigate the mechanistic role of lingual PYY in regulating appetite, energy intake and food preference in people with overweight/obesity.

Detailed Description
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In order to address the study objective two independent investigations in two separate groups of participants will need to be undertaken, to avoid cross-contamination of the results. Cohort/Investigation 1: A randomised within-subject double-blind cross-over placebo-controlled study to investigate the role of lingual PYY in regulating fasted and post-meal appetite following a fixed energy intake meal. Cohort/Investigation 2: A randomised within-subject double-blind cross-over placebo-controlled study to investigate the role of lingual PYY in regulating ad libitum energy intake and food preference. People with overweight or obesity (BMI 25.0-39.9 kg/m2), identified via the University College London Hospitals (UCLH) Bariatric Centre for Weight Management and Metabolic Surgery and through advertising via University College London (UCL) and ULCH, will be invited to take part. Potential participants will initially attend a screening visit, where informed, written consent will first be taken. During the screening visit, medical, drug and dietary histories will be taken and participant eligibility will be confirmed. Participants will attend on two separate occasions at least 7 days apart for both cohort/investigation 1 and cohort/investigation 2. 20 participants per cohort/investigation will be randomised (in a 1:1 manner), stratified by sex, to receive either oral PYY3-36 solution or matched placebo at their first study visit. Participants will be recruited onto study/investigation 1 first and once this is complete, new subjects will be enrolled onto study/investigation 2. Cohort/Intervention 1: The day prior to each visit participants will complete a 24 hour food diary and appetite scores at home. Participants will fast overnight (12 hours) and consume only water until reaching the clinical facility the following morning. Participants will need to refrain from exercise for 2 days prior to the study visits and from drinking alcohol. On arrival, medical history will be re-reviewed, sociodemographic information collected and a pregnancy test for women of childbearing potential will be performed. Body weight and composition will be measured. Baseline assessments of fasted subjective appetite assessed using validated visual analogue scales (VAS), saliva PYY levels (via saliva sample) and circulating gut hormones (via blood sample) will be taken. A single dose of lingual PYY (GT-001) or placebo will be administered. Appetite scores and a paired blood and saliva sample will be collected 10-15 minutes later. 30 minutes after study drug application, participants will then be asked to consume a standardised fixed meal over 15 minutes using established protocol and appetite scores (VAS) and saliva and blood samples will be taken for 180 minutes post-meal at regular intervals. Participants will be asked to complete 24-hour food diary and appetite scores 6, 12 and 24 hours after the study visit. Cohort/Intervention 2: The day prior to each study visit participants will complete a 24-hour food diary and appetite scores at home. Participants will fast overnight (12 hours) and consume only water until reaching the clinical facility the following morning. Participants will need to refrain from exercise for 2 days prior to the study visits and from drinking alcohol. On arrival, medical history will be re-reviewed, sociodemographic information collected and a pregnancy test for women of childbearing potential will be performed. Body weight and composition will be measured. Baseline assessments of fasted subjective appetite assessed using validated VAS, saliva PYY levels (via saliva sample) and circulating gut hormones (via blood sample) will be taken. A single dose of lingual PYY (GT-001) or placebo will be administered. Appetite scores and a paired blood and saliva sample will be collected 10-15 minutes later. 30 minutes after study drug application, participants will be offered an extensive free-choice buffet lunch and asked to eat until full. Ad libitum energy intake and food preferences will be assessed. Participants will be asked to rank likeness of the items of the buffet. Appetite scores (VAS) and paired blood and saliva sample will be taken again 60 minutes from the onset of the meal. Participants will be asked to complete 24-hour food diary and appetite scores 24 hours after the study visit. After a 7-day washout period participants in each cohort/intervention will be crossed-over and the same visit will be repeated. Both the participants and researchers will be blinded to the study condition.

Official Title
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A Double-blind, Cross-over, Placebo-controlled, Proof-of-concept Study Using Oral Peptide YY3-36 Solution to Investigate the Mechanistic Role of Lingual PYY in Regulating Appetite, Energy Intake and Food Preference in People With Overweight/Obesity

Conditions
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Obesity

Intervention / Treatment
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* Drug: PYY (3-36) Peptide
* Drug: Placibo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Adults aged 18-65 inclusive. 2. People with a body mass index (BMI) between 25.0 and 39.9 kg/m2 3. Stable weight for past 3 months (≤5% change in preceding 3 months as reported by participants). 4. Females of childbearing potential must be on highly effective contraception and have a negative pregnancy test within 7 days of their study visits. NOTE: Subjects are considered not of childbearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. 5. Fluent in English and able to understand and complete questionnaires. 6. Willing and able to provide written informed consent and comply with the study protocol. Exclusion Criteria: Female subjects who are pregnant or breast-feeding. Female subjects of childbearing potential who are not on highly effective contraception. Post-menopausal women who have not had a period of spontaneous amenorrhea for more than 1 year. Previous bariatric surgery. Type 1 or 2 diabetes. Current use of weight loss medications or taking medication that affects appetite, e.g., antidepressants such as mirtazapine. Food intolerances, or allergies, that would make fixed energy meal and/or ad libitum meal unable to be performed. Impairment of sense of taste and/or smell, as per subject assessment and direct questioning. Poor dental hygiene or oral pathology. Current smokers of tobacco products. Any other factor making the participant unsuitable in the view of investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort/Intervention 1<br>Meal test | Drug: PYY (3-36) Peptide<br>* oral PYY3-36 solution<br>Drug: Placibo<br>* oral placebo solution<br>|
| Cohort/Intervention 2<br>Ad libitum meal | Drug: PYY (3-36) Peptide<br>* oral PYY3-36 solution<br>Drug: Placibo<br>* oral placebo solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| appetite scores | area-under-the curve for appetite scores. Not indicative of either bad or worse outcome, just subjective indication. | up to 6 hours | 
| energy intake expressed as Kcal of eaten food | ad libitum energy intake | up to 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PYY levels | Area-under-the-curve for saliva PYY levels | up to 6 hours | 
| gut hormones levels | Area-under-the-curve for gut hormones levels | up to 6 hours | 
| 24-h energy intake |  | 24 hours after study visit | 
| 24h appetite | Subjective appetite scores for 24 hours following a fixed meal using VAS - a 1 to 10 scale will be used where the higher the score the higher the level of feeling of the item for the subject. No better or worse meaning applied a priory. | 24 hours after study visit | 
| macronutrient selection | Macronutrient content of consumed food during ad libitum meal | up to 1 hour | 
| food preference using labelled magnitude scales (LMS) | labelled magnitude scales (LMS) for components of the ad libitum meal | through study completion, an average of 6 hours | 
| food preference questionnaire (FPQ) | The food preference questionnaire requires participants to rate their liking of 62 individual foods on a 5-point Likert scale, ranging from not at all to a lot. A higher score indicative of greater liking of a food. | once, at beginning of study visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity, appetite