Impact of Sweeteners on Behaviour, Physiology & Health

Study Overview
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Brief Summary
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This study aims to evaluate the acute (1-day) and repeated (2-week) effects of combinations of Sweeteners & Sweetness Enhancer blends on metabolic, sensory, neuro-behavioural and microbiota-mediated processes involved in satiety, consumer preferences and health.

Detailed Description
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This protocol has the overall objective to evaluate the acute (short-term, 1 day) and repeated (medium-term, 2 week) effects of combinations of sweeteners and sweetness enhancers (S&SEs) on metabolic, sensory, neuro-behavioural and microbiota-mediated processes involved in satiety, consumer preference and health, and to explore mechanistic processes, genetic background, safety issues and consumer perspectives. There are 5 products being tested in 3 different formulations (sucrose-sweetened control vs 2 reformulated with S&SE). Each product will be tested at 2 intervention sites in double-blind cross-over trials with 48 subjects (24 per site) tested per product. Therefore a total of 240 subjects will take part across the 5 intervention sites (Navarra, Leeds, Liverpool, Copenhagen, Lyon). Using identical procedures each trial will consist of 2 Clinical Investigation Days (CIDs) scheduled 12 days apart for each of the 3 product formulations. A 2-week wash-out period will be given between formulations. The total duration of WP2 Phase 2 is 12 months, including a 5-month duration for each cross-over trial.

Official Title
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Acute and Repeated Impact of Sweeteners and Sweetness Enhancers on Food Behaviour, Physiology & Health (SWEET Work Package 2 Phase 2)

Conditions
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Eating Behavior

Intervention / Treatment
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* Dietary Supplement: Sweetener and sweetness enhancer consumption


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI: 25 to 35 kg/m2 Use of contraceptive methods or not planning to become pregnant for the duration of the study (women only) Regular consumption of sugar-containing foods and willing to consume sugar and artificially-sweetened food products. Liking of the intervention foods defined by a response of Yes for the product during the pre-screening interview and a score of 40% or above on the Liking Visual Analogue Scale for the sucrose-sweetened control product. Able to participate on the Clinical Investigation Days during normal working hours. Healthy as determined from the self-reported medical history or when a clinical condition exists, when this is considered to be irrelevant (i.e. not influencing study outcomes) for the study by the study medical doctor. Consuming breakfast regularly (at least 5 days per week). Able to understand and be willing to sign the informed consent form, and to follow all the study procedures and requirements. Capacity to store at-home intervention quantity of intervention product Exclusion Criteria: Blood donation < 3 month prior to study or for full duration of the study. Food allergy, intolerance, restriction or avoidance of any of the study foods (e.g. veganism) or history of anaphylactic reaction to any food. Likelihood for disordered eating defined as a score ≥20 on the Eating Attitudes Test. Currently dieting to lose weight. Having lost or gained >4.5 kg in the last 3 months. Smoking or having quit <3 months prior to study. Habitually consuming >14 units/week of alcohol in women or >21 units/week in men in the last 3 months. Performing >10 h of intense physical activity per week in the last 3 months. Night or late shift work (ending later than 11 pm on a permanent basis). Rotational shift work allowed if can attend on days that do not follow a late/night shift. Self-reported use of drugs of abuse within the previous 12 months. Pregnancy, lactation (women only) Persons who do not have access to either (mobile) phone or internet (this is necessary when being contacted by the study personnel during the study). Insufficient communication in the national language. Proven or suspected inability, physically or mentally, to comply with the procedures required by the study protocol as evaluated by the daily study manager, site-PI, PI or clinical responsible. This includes volunteers for which insufficient collaboration may be foreseen. Subject's general condition contraindicates continuing in the study as evaluated by the daily study manager, site-PI, PI or responsible clinician. Simultaneous participation in other relevant clinical intervention studies. Previous university or college training related to eating behaviour research. Self-reported eating disorders. Diagnosed anaemia. Diagnosed diabetes mellitus. Abnormal G.I. function or structure such as malformation, angiodysplasia, active peptic ulcer. Active inflammatory bowel disease, celiac disease, chronic pancreatitis or other disorder potentially causing malabsorption. History of G.I. surgery with permanent effect (i.e. surgical treatment of obesity). Medical history of Cardiovascular Disease (e.g. current angina; myocardial infarction or stroke within the past 6 months; heart failure; symptomatic peripheral vascular disease). Significant liver disease, e.g. cirrhosis (fatty liver disease allowed). Malignancy which is currently active or in remission for less than five years after last treatment (local basal and squamous cell skin cancer allowed). Thyroid diseases, except those on Levothyroxine treatment of hypothyroidism if the person has been on a stable dose for at least 3 months. Psychiatric illness (e.g. major depression, bipolar disorders). Use currently or within the previous 3 months of prescription or over the counter medication that has the potential of affecting appetite, satiety or body weight incl. food supplements. Except: low dose antidepressants if they, in the judgement of the daily study manager, site-PI, PI or clinical responsible, do not affect weight or following the study protocol. Levothyroxine for treatment of hypothyroidism is allowed if the person has been on a stable dose for at least 3 months. Cholesterol lowering medication, if the dose has changed during the last 3 months (i.e. the medication is allowed if the participant has been on a stable dose for at least 3 months).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-blind, within-subjects, cross-over trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cake matrix<br>3 phases of 2-week daily consumption of cake product containing 1) sucrose, 2) Neotame 1, 3) Stevia Reb M. Randomised cross-over with 2-week wash-out between phases. | Dietary Supplement: Sweetener and sweetness enhancer consumption<br>* Two-week consumption of combinations of different sweetener and sweetness enhancer blends in reformulated food products compared to sucrose containing product.<br>|
| Experimental: Biscuit matrix<br>3 phases of 2-week daily consumption of biscuit product containing 1) sucrose, 2) Neotame 1, 3) Stevia Reb M. Randomised cross-over with 2-week wash-out between phases. | Dietary Supplement: Sweetener and sweetness enhancer consumption<br>* Two-week consumption of combinations of different sweetener and sweetness enhancer blends in reformulated food products compared to sucrose containing product.<br>|
| Experimental: Yoghurt matrix<br>3 phases of 2-week daily consumption of yoghurt product containing 1) sucrose, 2) sweetener blend 1, 3) sweetener blend 2. Randomised cross-over with 2-week wash-out between phases. | Dietary Supplement: Sweetener and sweetness enhancer consumption<br>* Two-week consumption of combinations of different sweetener and sweetness enhancer blends in reformulated food products compared to sucrose containing product.<br>|
| Experimental: Chocolate matrix<br>3 phases of 2-week daily consumption of chocolate product containing 1) sucrose, 2) sweetener blend 1, 3) sweetener blend 2. Randomised cross-over with 2-week wash-out between phases. | Dietary Supplement: Sweetener and sweetness enhancer consumption<br>* Two-week consumption of combinations of different sweetener and sweetness enhancer blends in reformulated food products compared to sucrose containing product.<br>|
| Experimental: Cereal matrix<br>3 phases of 2-week daily consumption of cereal product containing 1) sucrose, 2) sweetener blend 1, 3) sweetener blend 2. Randomised cross-over with 2-week wash-out between phases. | Dietary Supplement: Sweetener and sweetness enhancer consumption<br>* Two-week consumption of combinations of different sweetener and sweetness enhancer blends in reformulated food products compared to sucrose containing product.<br>|
| Experimental: Universal Eating Monitor study<br>A sub-group of the yoghurt matrix will be selected for assessment of eating rate and microstructure of feeding using Universal Eating Monitors. | Dietary Supplement: Sweetener and sweetness enhancer consumption<br>* Two-week consumption of combinations of different sweetener and sweetness enhancer blends in reformulated food products compared to sucrose containing product.<br>|
| Experimental: fMRI study<br>A sub-group of the chocolate matrix will be selected for assessment of neural activation to images of food using fMRI. | Dietary Supplement: Sweetener and sweetness enhancer consumption<br>* Two-week consumption of combinations of different sweetener and sweetness enhancer blends in reformulated food products compared to sucrose containing product.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Appetite Sensations Incremental Area Under the Curve | Incremental area under the curve (iAUC) for composite appetite sensations in response to each product. During each of the Clinical Investigation Days iAUC composite appetite will be measured 180 minutes post intake. The following sensations of appetite will be used in the composite measure: hunger fullness desire to eat prospective consumption Minimum value 0 Maximum value 100 Higher scores mean worse outcome | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leeds Food Preference Questionnaire (LFPQ) Explicit Liking | Change in explicit liking for foods at 15 min post intake Minimum value -100 Maximum value 100 Higher scores mean worse outcome | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 
| Leeds Food Preference Questionnaire (LFPQ) Implicit Wanting | Change in implicit wanting for foods at 15 min post intake Minimum value -100 Maximum value 100 Higher scores mean worse outcome | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 
| Leeds Food Preference Questionnaire (LFPQ) Relative preference | Change in relative preference for foods at 15 min post intake Minimum value -48 Maximum value 48 Higher scores mean worse outcome | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 
| Leeds Food Preference Questionnaire (LFPQ) Explicit wanting | Change in explicit wanting for foods at 15 min post intake Minimum value -100 Maximum value 100 Higher scores mean worse outcome | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 
| Control of Eating Questionnaire (CoEQ): Craving Control | Craving Control examined in a fasted state. Minimum value 0 Maximum value 100 Higher scores mean better outcome | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 
| Control of Eating Questionnaire (CoEQ): Craving for Sweet | Craving for Sweet examined in a fasted state. Minimum value 0 Maximum value 100 Higher scores mean worse outcome | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 
| Control of Eating Questionnaire (CoEQ): Craving for Savoury | Craving for Savoury examined in a fasted state. Minimum value 0 Maximum value 100 Higher scores mean worse outcome | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 
| Control of Eating Questionnaire (CoEQ): Positive Mood | Positive Mood examined in a fasted state. Minimum value 0 Maximum value 100 Higher scores mean better outcome | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 
| Blood Glucose Incremental Area Under the Curve | Incremental area under the curve for blood glucose concentrations in response to each product (120 min post intake). | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 
| Blood Insulin Incremental Area Under the Curve | Incremental area under the curve for blood insulin concentrations in response to each product (120 min post intake). | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 
| Cephalic and intestinal satiety biomarkers: Glucagon-like peptide-1 (GLP-1) | Incremental area under the curve for blood GLP-1 concentrations in response to each product (120 min post intake). | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 
| Cephalic and intestinal satiety biomarkers: Ghrelin | Incremental area under the curve for blood Ghrelin concentrations in response to each product (120 min post intake). | Clinical Investigation Day 1, 2, 3, 4, 5, 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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appetite, food preferences, sweeteners, sweetness enhancers