Clinical trial NCT04483180: Work Package 2 Phase 1 - Beverages Study
Official title: Sweeteners and Sweetness Enhancers: Short-term Impact on Food Behaviour, Physiology & Health (Phase 1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Glycemic Index
Overweight and Obesity
Lead sponsor: Clinica Universidad de Navarra, Universidad de Navarra
Sponsor class: OTHER
Collaborators: name: University of Leeds
name: University of Copenhagen
name: University of Liverpool
name: University of Surrey
name: Bioiatriki HEALTHCARE GROUP
First posted: 2020-07-23
Enrollment: 69
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: Multi-centre crossover study with 4 conditions using balanced block randomisation. The three centres will follow different randomisation sequences but will all test the same 4 conditions (University of Navarra, University of Copenhagen, University of Liverpool).
Primary purpose: SCREENING

Brief summary: Within the SWEET project (EU funded), in Work Package 2 there are two phases, this study refers to Phase 1 of the SWEET WP2 project, which will be a coordinated trial across 3 intervention centres, University of Navarra (UNAV), University of Liverpool (ULIV) and University of Copenhagen (UCPH). It will involve an acute intervention in 120 individuals to explore initial acceptance, safety and post-prandial effects of 3 S\&SE blends delivered in beverage format.

The main endpoints of the SWEET WP2 Phase 1 study will be glycaemic and lipaemic responses; eating behavior (subjective appetite, food preference, cravings, reward), and health effects (rebound hunger, G.I. side effects and metabolic effects). This phase will be exploratory and will not involve any specific primary hypotheses.

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 and neuro-behavioural processes involved in satiety, consumer preference and health, and to explore mechanistic processes, genetic background, safety issues and consumer perspectives.

There are 4 products being tested in 4 different formulations (sucrose-sweetened beverage control vs. 3 reformulated beverages with S\&SE). Each product will be tested at 3 intervention sites in double-blind cross-over trials with 40 subjects per site, tested per product. Therefore a total of 120 subjects will take part across the 3 intervention sites (UNAV, ULIV, UCPH).

Using identical procedures each trial will consist of 4 Clinical Investigation Days (CIDs) scheduled 7-11 days apart for each of the 3 product formulations.

The total duration of WP2 Phase 2 per site is 6 months, including a minimum of 22 days and a maximum of 34 days for each participant.

Eligibility criteria: Inclusion Criteria:

* Age: 18-60 years.
* BMI: 25 to 35 kg/m2.
* For women: Use of contraceptive methods or not planning to become pregnant for the duration of the study.
* Regular consumption of sugar-containing foods and willing to consume artificially-sweetened beverages (a score of ≥ 5 on the short sFFQ Part 1a and answer Yes to all questions in Part 2).
* Able to participate on the visit days/CIDs 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).
* Liking of the study foods defined by a response of Yes for each of the breakfast foods during the pre-screening interview and a score of 40 % or above on the Liking VAS for the control beverage.
* Able to understand and be willing to sign the informed consent form, and to follow all the study procedures and requirements.

Exclusion Criteria:

* Blood donation \< 3 month prior to study.
* Deficient nutrition or hydration status as identified from the pre-screening/screening session (i.e. absence of disease including anaemia, BMI \>18 kg/m2, or other criteria as determined by the study doctor).
* 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 of 20 or more on the EAT-26 test.
* Currently dieting to lose weight or having been on weight cycles (i.e. repeatedly lost and re-gained weight) in the last 3 months.
* Smoking.
* Binge drinking i.e. consuming \>14 units of alcohol per week in women or \>21 units/week in men less than 4 days apart.
* Performing \>10 h of intense physical activity per week.
* Continuous 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.
* For women: Pregnancy, lactation.
* 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 clinical responsible.
* Simultaneous participation in other relevant clinical intervention studies.
* Previous university or college training related to eating behaviour research.
* Medical conditions as known by the person:

  * Self-reported eating disorders.
  * Diagnosed anaemia.
  * Diagnosed diabetes mellitus.
  * Abnormal gastro-intestinal (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 cardio-vascular 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).
* Medication:

  * 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: Blood glucose area under the curve (AUC)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Blood Insulin AUC
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Hunger iAUC
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Fasting Blood glucose
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 30 min Blood glucose
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 60 min Blood glucose
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 90 min Blood glucose
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 120 min Blood glucose
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Fasting Blood insulin
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 30 min Blood insulin
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 60 min Blood insulin
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 90 min Blood insulin
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 120 min Blood insulin
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Fasting Hunger (VAS registered)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 5 min Hunger (VAS registered)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 15 min Hunger (VAS registered)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 30 min Hunger (VAS registered)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 45 min Hunger (VAS registered)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 60 min Hunger (VAS registered)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 120 min Hunger (VAS registered)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 180 min Hunger (VAS registered)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
Secondary outcomes:
measure: Fasting Blood cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 30 min Blood cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 60 min Blood cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 90 min Blood cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 120 min Blood cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Fasting Triglycerides
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 30 min Triglycerides
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 60 min Triglycerides
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 90 min Triglycerides
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 120 min Triglycerides
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Fasting HDL-cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 30 min HDL-cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 60 min HDL-cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 90 min HDL-cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 120 min HDL-cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Fasting LDL-cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 30 min LDL-cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 60 min LDL-cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 90 min LDL-cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 120 min LDL-cholesterol
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Fasting Alanine aminotransferase (ALT)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 120 min Alanine aminotransferase (ALT)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Fasting Aspartate aminotransferase (AST)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 120 min Aspartate aminotransferase (AST)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Weight
timeFrame: Visit 0 (screening), Clinical Investigation Day 4
measure: Height
timeFrame: Visit 0 (screening)
measure: Body Mass Index (BMI)
timeFrame: Visit 0 (screening), Clinical Investigation Day 4
measure: Waist Circumference (WC)
timeFrame: Visit 0 (screening)
measure: Hip Circumference (HC)
timeFrame: Visit 0 (screening)
measure: Waist-to-hip ratio (WHR)
timeFrame: Visit 0 (screening)
measure: Leeds Food Preference Questionnaire (LFPQ)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Liking (VAS registered)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Fasting FG21
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 30 min FG21
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 60 min FG21
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 90 min FG21
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: 120 min FG21
timeFrame: Clinical Investigation Day 1, 2, 3, 4
Other outcomes:
measure: Consumers' Perspectives Questionnaire
timeFrame: Visit 0 (screening)
measure: Blood DNA Analysis
timeFrame: Clinical Investigation Day 1
measure: 24 hour food recall
timeFrame: Next day after each clinical investigation day (1, 2, 3, 4)
measure: 24 hour Gastro Intestinal side effects
timeFrame: Next day after each clinical investigation day (1, 2, 3, 4)
measure: End of day questionnaire (VAS registered)
timeFrame: Clinical Investigation Day 1, 2, 3, 4
measure: Risk factors for chronic disease
timeFrame: Visit 0 (screening)
measure: Socio-demographic questionnaire
timeFrame: Visit 0 (screening)
measure: Eating Attitudes Test-26 (EAT-26)
timeFrame: Visit 0 (screening)
measure: Short sugar Food Frequency Questionnaire (short sFFQ)
timeFrame: Visit 0 (screening)
measure: End of study survey
timeFrame: Clinical Investigation Day 4
measure: Taste test (VAS registered)
timeFrame: Visit 0 (screening)
Locations:
city: Frederiksberg
country: Denmark
facility: University of Copenhagen
city: Pamplona
country: Spain
facility: Centre for Nutrition Research, University of Navarra
state: Navarra
city: Liverpool
country: United Kingdom
facility: University of Liverpool
Study officials:
References: