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| Name | Class |
|---|---|
| University of Navarra | OTHER |
| University of Liverpool | OTHER |
| Københavns Universitet | OTHER |
| Centre de Recherche en Nutrition Humaine Rhone-Alpe |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cake matrix | Experimental | 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. |
|
| Biscuit matrix | Experimental | 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. |
|
| Yoghurt matrix | Experimental | 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. |
|
| Chocolate matrix | Experimental | 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. |
|
| Cereal matrix | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sweetener and sweetness enhancer consumption | Dietary Supplement | Two-week consumption of combinations of different sweetener and sweetness enhancer blends in reformulated food products compared to sucrose containing product. |
| 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:
Minimum value 0 Maximum value 100 Higher scores mean worse outcome | Clinical Investigation Day 1, 2, 3, 4, 5, 6 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Body composition: fat mass (kg) | Anthropometry marker fat mass | Clinical Investigation Day 1, 2, 3, 4, 5, 6 |
| Body composition: fat-free mass (kg) | Anthropometry marker fat-free mass |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Copenhagen | Copenhagen | Denmark | ||||
| CRNH-RA |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36564114 | Derived | Gibbons C, O'Hara B, O'Connor D, Hardman C, Wilton M, Harrold JA, Almiron-Roig E, Navas-Carretero S, Hodgkins CE, Nazare JA, Alligier M, Martinez JA, Scott C, Kjolbaek L, Normand M, Rannou C, Blaak EE, Feskens E, Moshoyiannis H, Raben A, Halford JCG, Beaulieu K, Finlayson G. Acute and repeated impact of sweeteners and sweetness enhancers in solid and semi-solid foods on appetite: protocol for a multicentre, cross-over, RCT in people with overweight/obesity - the SWEET Project. BMJ Open. 2022 Dec 23;12(12):e063903. doi: 10.1136/bmjopen-2022-063903. |
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| ID | Term |
|---|---|
| D005247 | Feeding Behavior |
| D005518 | Food Preferences |
| ID | Term |
|---|---|
| D001522 | Behavior, Animal |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D013549 | Sweetening Agents |
| ID | Term |
|---|---|
| D005421 | Flavoring Agents |
| D005503 | Food Additives |
| D000074385 | Food Ingredients |
| D020313 | Specialty Uses of Chemicals |
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| OTHER |
| University of Surrey | OTHER |
| Bioatriki Healthcare Group | UNKNOWN |
Double-blind, within-subjects, cross-over trial
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Double blind study. Neither the participant nor the investigator will be aware of the coding of food products used in the study.
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.
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| Universal Eating Monitor study | Experimental | A sub-group of the yoghurt matrix will be selected for assessment of eating rate and microstructure of feeding using Universal Eating Monitors. |
|
| fMRI study | Experimental | A sub-group of the chocolate matrix will be selected for assessment of neural activation to images of food using fMRI. |
|
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 |
| Clinical Investigation Day 1, 2, 3, 4, 5, 6 |
| Body weight (kg) | Anthropometry marker body weight | Fasting during each Clinical Investigation Day 1, 2, 3, 4, 5, 6 |
| Standing height (cm) | Anthropometry marker standing height | Measured in a fasting state during screening day only |
| Waist circumference (cm) | Anthropometry marker waist circumference | Fasting during each Clinical Investigation Day 1, 2, 3, 4, 5, 6 |
| 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 |
| Sweet taste receptor polymorphism prevalence | Blood DNA analysis for sweet taste receptor polymorphism prevalence | Clinical Investigation Day 1 only in a fasted state |
| Consumers' Perspectives Questionnaire on sweeteners | Psychological health drivers (perceptions) of sweetener consumption | Fasted state on screening day only (Day 0) |
| 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. |
| 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. |
| 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 |
| 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 |
| 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 |
| 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) |
| 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) |
| 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) |
| 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) |
| Habitual intake of sweet foods | Short sugar Food Frequency Questionnaire (short sFFQ) | Fasted state on screening day only (Day 0) |
| Perception and evaluation of the clinical trial | End of study survey | Clinical Investigation Day 6 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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. |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| HbA1c | Fasting HbA1c blood concentrations | Measured in a fasting state during Clinical Investigation Day 1 and 6 only |
| 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 |
| 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 |
| Lyon |
| France |
| University of Navarra | Pamplona | 31009 | Spain |
| University of Leeds | Leeds | West Yorkshire | LS2 9JT | United Kingdom |
| University of Liverpool | Liverpool | United Kingdom |
| D020164 |
| Chemical Actions and Uses |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |