Impact of Sweeteners on Behaviour, Physiology & Health

Eating Behavior Clinical Trial

— SWEET-WP2-P2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04633681
• Other study ID #: 774293-WP2-P2
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2021
• Est. completion date: September 30, 2023

Study information

• Verified date: January 2023
• Source: University of Leeds
• Contact: Graham S Finlayson, PhD
• Phone: +441133437601
• Email: g.s.finlayson[@]leeds.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: September 30, 2023
• Est. primary completion date: July 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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).

Related Conditions & MeSH terms

• Eating Behavior

Intervention

Dietary Supplement:
• Sweetener and sweetness enhancer consumption
Two-week consumption of combinations of different sweetener and sweetness enhancer blends in reformulated food products compared to sucrose containing product.

Locations

Country	Name	City	State
Denmark	University of Copenhagen	Copenhagen
France	CRNH-RA	Lyon
Spain	University of Navarra	Pamplona
United Kingdom	University of Leeds	Leeds	West Yorkshire
United Kingdom	University of Liverpool	Liverpool

Sponsors (7)

Lead Sponsor	Collaborator
University of Leeds	Bioatriki Healthcare Group, Centre de Recherche en Nutrition Humaine Rhone-Alpe, Københavns Universitet, University of Liverpool, University of Navarra, University of Surrey

Countries where clinical trial is conducted

Denmark,  France,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body composition: fat mass (kg)	Anthropometry marker fat mass	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Body composition: fat-free mass (kg)	Anthropometry marker fat-free mass	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Body weight (kg)	Anthropometry marker body weight	Fasting during each Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Standing height (cm)	Anthropometry marker standing height	Measured in a fasting state during screening day only
Other	Waist circumference (cm)	Anthropometry marker waist circumference	Fasting during each Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Body composition, body weight, height, waist and hip circumference	Anthropometry marker hip circumference	Fasting during each Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Sweet taste receptor polymorphism prevalence	Blood DNA analysis for sweet taste receptor polymorphism prevalence	Clinical Investigation Day 1 only in a fasted state
Other	Consumers' Perspectives Questionnaire on sweeteners	Psychological health drivers (perceptions) of sweetener consumption	Fasted state on screening day only (Day 0)
Other	Gut microbiota profile (diversity and ratio)	Gut microbiota measured from fecal samples during clinical investigation days in yoghurt matrix only	Collected the day before each Clinical Investigation Day for the yoghurt food matrix.
Other	Brain activity (fMRI)	Neural activation to chocolate matrix only	Clinical Investigation Day 1 and Clinical Investigation Day 6 immediately before and immediately after consumption of the chocolate food matrix.
Other	Meal eating behaviour and microstructure: Eating rate	Eating rate using the Universal Eating Monitor in yoghurt matrix only	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Meal eating behaviour and microstructure: Bite count	Bite count using the Universal Eating Monitor in yoghurt matrix only	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Urinary S&SEs biomarkers	Biomarkers of S&SE quality measured from urine samples	Collected the day before each Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Eating behaviour traits: Three factor eating questionnaire Restraint subscale	Restraint eating behaviour trait measured by the Three Factor Eating Questionnaire.; Minimum value 0 Maximum value 21 Higher scores mean worse outcome	Fasted state on screening day only (Day 0)
Other	Eating behaviour traits: Three factor eating questionnaire Hunger subscale	Hunger eating behaviour trait measured by the Three Factor Eating Questionnaire.; Minimum value 0 Maximum value 14 Higher scores mean worse outcome	Fasted state on screening day only (Day 0)
Other	Eating behaviour traits: Three factor eating questionnaire Disinhibition subscale	Disinhibition eating behaviour trait measured by the Three Factor Eating Questionnaire.; Minimum value 0 Maximum value 16 Higher scores mean worse outcome	Fasted state on screening day only (Day 0)
Other	Eating behaviour traits: Binge Eating Scale	Binge Eating measured by the Binge Eating Scale; Minimum value 0 Maximum value 46 Higher scores mean worse outcome	Fasted state on screening day only (Day 0)
Other	Habitual intake of sweet foods	Short sugar Food Frequency Questionnaire (short sFFQ)	Fasted state on screening day only (Day 0)
Other	Perception and evaluation of the clinical trial	End of study survey	Clinical Investigation Day 6
Other	24-h Dietary recall: Self-reported energy intake	Interview to know what the volunteers ate during the 24h following each probe day	Next day after each Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	24-h Dietary recall: Energy compensation after intake of intervention products	Interview to know what the volunteers ate during the 24h following each probe day accounting for the energy contained in the intervention food products	Next day after each Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Expected satiety	Single-item Visual Analogue Scale assessing expected satiety from the intervention food products Minimum value 0 Maximum value 100 Higher scores mean better outcome	Immediately before consuming food product during each Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Sensory-specific satiety	Single-item Visual Analogue Scale assessing sensory-specific satiety from the intervention food products Minimum value 0 Maximum value 100 Higher scores mean better outcome	Immediately before and immediately after consuming food product during each Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Thirst Incremental Area Under the Curve	Incremental area under the curve (iAUC) for thirst in response to each product.; During each of the Clinical Investigation Days iAUC thirst will be measured 180 minutes post intake using visual analogue scale.; Minimum value 0 Maximum value 100 Higher scores mean worse outcome	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Nausea Incremental Area Under the Curve	Incremental area under the curve (iAUC) for nausea in response to each product.; During each of the Clinical Investigation Days iAUC nausea will be measured 180 minutes post intake using visual analogue scale.; Minimum value 0 Maximum value 100 Higher scores mean a worse outcome.	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Bloating Incremental Area Under the Curve	Incremental area under the curve (iAUC) for bloating in response to each product.; During each of the Clinical Investigation Days iAUC bloating will be measured 180 minutes post intake using visual analogue scale.; Minimum value 0 Maximum value 100 Higher scores mean worse outcome	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Cephalic and intestinal satiety biomarkers: Pancreatic polypeptide (PP)	Incremental area under the curve for blood PP concentrations in response to each product (120 min post intake).	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.
Other	Lipaemia: triglycerides	Incremental area under the curve for blood triglyceride concentrations in response to each product (120 min post intake).	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Lipaemia: Cholesterol (total)	Incremental area under the curve for blood cholesterol (total) concentrations in response to each product (120 min post intake).	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Lipaemia: Cholesterol (HDL)	Incremental area under the curve for blood cholesterol (HDL) concentrations in response to each product (120 min post intake).	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Lipaemia: Cholesterol (LDL)	Incremental area under the curve for blood cholesterol (LDL) concentrations in response to each product (120 min post intake).	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Liver function: Alanine aminotransferase (ALT)	Mean of liver function marker (ALT) concentrations in response to each product (120 min post intake).	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Liver function: Aspartate aminotransferase (AST)	Mean of liver function marker (AST) concentrations in response to each product 120 min post intake.	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Liver function: Gamma-Glutamyl Transpeptidase (GGT)	Mean of liver function marker (GGT) concentrations in response to each product 120 min post intake.	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Liver function: Fatty Liver index	Mean of liver function marker (FL index) concentrations in response to each product 120 min post intake.	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	Liver function: Triglyceride index	Mean of liver function marker (TyG index) concentrations in response to each product 120 min post intake.	Clinical Investigation Day 1, 2, 3, 4, 5, 6
Other	HbA1c	Fasting HbA1c blood concentrations	Measured in a fasting state during Clinical Investigation Day 1 and 6 only
Other	24 hour Gastrointestinal side effects	GI side effects reported in a booklet to know if the volunteers experience side effects during the intervention periods	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
Other	Adverse events	Adverse event reported in a booklet to know if the volunteers experience side effects during the intervention periods	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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