Clinical trial NCT04633681: Impact of Sweeteners on Behaviour, Physiology & Health
Official title: Acute and Repeated Impact of Sweeteners and Sweetness Enhancers on Food Behaviour, Physiology & Health (SWEET Work Package 2 Phase 2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Eating Behavior
Keywords: appetite
food preferences
sweeteners
sweetness enhancers
Lead sponsor: University of Leeds
Sponsor class: OTHER
Collaborators: name: University of Navarra
name: University of Liverpool
name: Københavns Universitet
name: Centre de Recherche en Nutrition Humaine Rhone-Alpe
name: University of Surrey
name: Bioatriki Healthcare Group
First posted: 2020-11-18
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blind, within-subjects, cross-over trial
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Composite Appetite Sensations Incremental Area Under the Curve
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
Secondary outcomes:
measure: Leeds Food Preference Questionnaire (LFPQ) Explicit Liking
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Leeds Food Preference Questionnaire (LFPQ) Implicit Wanting
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Leeds Food Preference Questionnaire (LFPQ) Relative preference
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Leeds Food Preference Questionnaire (LFPQ) Explicit wanting
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Control of Eating Questionnaire (CoEQ): Craving Control
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Control of Eating Questionnaire (CoEQ): Craving for Sweet
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Control of Eating Questionnaire (CoEQ): Craving for Savoury
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Control of Eating Questionnaire (CoEQ): Positive Mood
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Blood Glucose Incremental Area Under the Curve
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Blood Insulin Incremental Area Under the Curve
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Cephalic and intestinal satiety biomarkers: Glucagon-like peptide-1 (GLP-1)
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Cephalic and intestinal satiety biomarkers: Ghrelin
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other outcomes:
measure: Body composition: fat mass (kg)
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Body composition: fat-free mass (kg)
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Body weight (kg)
timeFrame: Fasting during each Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Standing height (cm)
timeFrame: Measured in a fasting state during screening day only
measure: Waist circumference (cm)
timeFrame: Fasting during each Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Body composition, body weight, height, waist and hip circumference
timeFrame: Fasting during each Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Sweet taste receptor polymorphism prevalence
timeFrame: Clinical Investigation Day 1 only in a fasted state
measure: Consumers' Perspectives Questionnaire on sweeteners
timeFrame: Fasted state on screening day only (Day 0)
measure: Gut microbiota profile (diversity and ratio)
timeFrame: Collected the day before each Clinical Investigation Day for the yoghurt food matrix.
measure: Brain activity (fMRI)
timeFrame: Clinical Investigation Day 1 and Clinical Investigation Day 6 immediately before and immediately after consumption of the chocolate food matrix.
measure: Meal eating behaviour and microstructure: Eating rate
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Meal eating behaviour and microstructure: Bite count
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Urinary S&SEs biomarkers
timeFrame: Collected the day before each Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Eating behaviour traits: Three factor eating questionnaire Restraint subscale
timeFrame: Fasted state on screening day only (Day 0)
measure: Eating behaviour traits: Three factor eating questionnaire Hunger subscale
timeFrame: Fasted state on screening day only (Day 0)
measure: Eating behaviour traits: Three factor eating questionnaire Disinhibition subscale
timeFrame: Fasted state on screening day only (Day 0)
measure: Eating behaviour traits: Binge Eating Scale
timeFrame: Fasted state on screening day only (Day 0)
measure: Habitual intake of sweet foods
timeFrame: Fasted state on screening day only (Day 0)
measure: Perception and evaluation of the clinical trial
timeFrame: Clinical Investigation Day 6
measure: 24-h Dietary recall: Self-reported energy intake
timeFrame: Next day after each Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: 24-h Dietary recall: Energy compensation after intake of intervention products
timeFrame: Next day after each Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Expected satiety
timeFrame: Immediately before consuming food product during each Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Sensory-specific satiety
timeFrame: Immediately before and immediately after consuming food product during each Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Thirst Incremental Area Under the Curve
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Nausea Incremental Area Under the Curve
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Bloating Incremental Area Under the Curve
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Cephalic and intestinal satiety biomarkers: Pancreatic polypeptide (PP)
timeFrame: During each of the probe day visits blood pancreatic polypeptide (PP) will be measured at baseline, and 5, 10, 30 minutes after consuming the product. Each visit will be separated by 12 days of daily consumption of the product.
measure: Lipaemia: triglycerides
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Lipaemia: Cholesterol (total)
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Lipaemia: Cholesterol (HDL)
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Lipaemia: Cholesterol (LDL)
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Liver function: Alanine aminotransferase (ALT)
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Liver function: Aspartate aminotransferase (AST)
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Liver function: Gamma-Glutamyl Transpeptidase (GGT)
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Liver function: Fatty Liver index
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: Liver function: Triglyceride index
timeFrame: Clinical Investigation Day 1, 2, 3, 4, 5, 6
measure: HbA1c
timeFrame: Measured in a fasting state during Clinical Investigation Day 1 and 6 only
measure: 24 hour Gastrointestinal side effects
timeFrame: Up to 24 hours after each Clinical Investigation Day and from Clinical Investigation Day 1, 2, 3, 4, 5, 6 during the 3 at home intervention periods up to 12 days
measure: Adverse events
timeFrame: Up to 24 hours after each Clinical Investigation Day and from Clinical Investigation Day 1, 2, 3, 4, 5, 6 during the 3 at home intervention periods up to 12 days
Locations:
city: Copenhagen
country: Denmark
facility: University of Copenhagen
city: Lyon
country: France
facility: CRNH-RA
city: Pamplona
country: Spain
facility: University of Navarra
city: Leeds
country: United Kingdom
facility: University of Leeds
state: West Yorkshire
city: Liverpool
country: United Kingdom
facility: University of Liverpool
Study officials:
References: