Sweeteners and Sweetness Enhancers: Prolonged Effects on Health, Obesity and Safety
- Conditions
- Obesity
- Interventions
- Behavioral: SugarBehavioral: S&SEs
- Registration Number
- NCT04226911
- Lead Sponsor
- Anne Birgitte Raben
- Brief Summary
The aim of this randomised controlled trial (RCT) is to investigate if prolonged consumption of sweetener and sweetness enhancers (S\&SEs) within a healthy diet approach will improve weight loss maintenance and obesity related risk factors, and affect safety markers, compared to sugar.
We hypothesize, that:
* Prolonged use of S\&SEs in beverages and food matrices will result in improved body weight control because S\&SEs will increase palatability of the diet and thereby increase compliance to the recommendations for a healthy diet.
* There will be no safety concerns using S\&SEs in the long term.
Overweight/obese adults and families where at least one adult (both gender) and one child (both gender) are overweight/obese will be recruited. The majority of measurements will only be conducted in the adult population and some measurement will only be done in sub-groups. The intervention will be performed in four countries: Denmark, Greece, Spain and the Netherlands.
The goal is approximately 370 participants - 330 adults (18-65 years of age) and 40 children (6-12 years of age) - will be recruited for the study. All adult participants are first treated by a low energy diet (LED) for 2 months with the aim to reduce body weight (minimum 5% weight loss (WL)), whereas children are treated separately with a conventional weight maintenance (WM) diet, without a specific aim for absolute WL.
The participants - both adults and families - are randomized into two different diet interventions for 10 months with or without inclusion of S\&SEs products (foods and drinks). For adults, this period aims at preventing weight re-gain and for children maintaining body mass index (BMI)-for-age. The participants will receive food exchange lists and will be guided by dieticians. The randomization will be stratified by age, sex and BMI. Adults (not participating with children) belonging to the same household and all members of a family will be assigned the same intervention - the randomization will here solely be based on the oldest adult in the family/household.
The adult participants are weighed at months 0, 0.5 and 1, and if needed at month 1.5. They are supervised during the WL period at months 0 and 1, and if needed at months 0.5 and 1.5, and throughout the WM period at months 2, 4, 6, 9 and 12. Children will follow a similar, but less strict time schedule (their participation is preferred but not required for all dietician meetings).
The main assessment points are the clinical investigation days (CIDs) at month 0 (baseline, start of the WL period), 2 (end of the WL period/start of randomized intervention), 6 (6 months from baseline) and 12 (1 year from baseline).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 379
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sugar group Sugar Healthy diet, \< 10 E% sugar, foods and drinks with S\&SEs not allowed. Sweeteners and sweetness enhancers (S&SEs) S&SEs Healthy diet \< 10 energy % (E%) sugar, foods and drinks with S\&SEs allowed.
- Primary Outcome Measures
Name Time Method Change in body weight (adults) Up to 1 year. Efficacy: Change in body weight will be measured by a calibrated digital scale.
Changes in gut microbiota composition (adults) Up to 1 year. Safety: Change in gut microbiota associated with impaired health (e.g. change in microbial beta-diversity and composition) will be measured by fecal samples.
- Secondary Outcome Measures
Name Time Method Change in BMI-for-age z-score (children) Up to 1 year. Efficacy: Efficacy: BMI-for-age z-score will be calculated based on the childrens weight and height using WHO AnthroPlus.
Changes in waist and hip circumferences (adults and children) Up to 1 year. Efficacy: Changes in waist and hip circumferences will be measured with a non-elastic tape.
Change in body composition (adults and children) Up to 1 year. Efficacy: Body composition will be measured using Dual X-rays. Children are not DXA scanned at UM.
Change in blood pressure and heart rate (adults and children) Up to 1 year. Efficacy: Change in blood pressure will be measured by an automatic device on the right arm.
Change in hemoglobin A1c (adults and children) Up to 1 year. Efficacy: Change in hemoglobin A1c will be measured by fasting blood samples.
Change in alanine aminotransferase (ALT) (adults and children) Up to 1 year. Efficacy: Change in ALT will be measured by fasting blood samples.
Change in insulinemia (adults and children) Up to 1 year. Efficacy: Change in insulinemia (insulin) will be measured by fasting blood samples.
Change in glucose (adults and children) Up to 1 year. Efficacy: Change in glucose will be measured by fasting blood samples.
Change in aspartate aminotransferase (AST) (adults and children) Up to 1 year. Efficacy: Change in AST will be measured by fasting blood samples.
Change in lipidemia (adults and children) Up to 1 year. Efficacy: Change in lipidemia (total cholesterol, high-density cholesterol, low-density cholesterol, triglycerides) will be measured by fasting blood samples.
Allergenicity by a skin prick test (adults) Up to 1 year. Safety: To assess allergenicity a skin prick test will be performed.
Allergenicity by a questionnaire (adults and children) Up to 1 year. Safety: To assess allergenicity a questionnaire will be completed.
Concomitant medication (adults and children) Up to 1 year. Safety: Concomitant medication will be reported in a case report from designed for the purpose.
Adverse events (adults and children) Up to 1 year. Safety: Adverse events will be reported in a case report form designed for the purpose e.g. headache, constipation ect.
Change C-reactive protein (CPR) (adults and children) Up to 1 year. Efficacy: Change in CPR will be measured by fasting blood samples.
Change in liver fat and lipid composition (adults) Up to 1 year. Safety: Change in liver fat and lipid composition will be measured by magnet resonans (MR) scans in a sub-group (UM).
Change in FGF21 (adults) Up to 1 year. Efficacy: Change in FGF21 will be measured in a sub-group by fasting blood samples (UCPH).
Allergenicity by serum immunoglobulin level (adults and children) Up to 1 year. Safety: To assess allergenicity serum immunoglobulin levels will be measured by fasting blood samples.
Change in ghrelin (adults) Up to 1 year. Efficacy: Change in ghrelin will be measured in a sub-group by fasting blood samples (UCPH, UM).
Change in cholecystokinin (adults) Up to 1 year. Efficacy: Change in cholecystokinin will be measured in a sub-group by fasting blood samples (UCPH, UM).
Change in glucagon-like peptide-1 (GLP-1) (adults) Up to 1 year. Efficacy: Change in GLP-1 will be measured in a sub-group by fasting blood samples (UCPH, UM).
Changes in gut microbiota composition (children) Up to 1 year. Safety: Change in gut microbiota associated with impaired health (e.g. change in microbial beta-diversity and composition) will be measured by fecal samples in a sub-group (UM)
Markers of adipogenesis (adults) Up to 1 year. Safety: Markers of adipogenesis will be measured by a adipose tissue biopsy (needle biopsy) in a sub-group (UM).
Fat cell size (adults) Up to 1 year. Safety: Change in fat cell size will be measured by a adipose tissue biopsy (needle biopsy) in a sub-group (UM).
Changes in gut-microbial composition in response to specific S&SEs in vitro (adults) Only baseline feces samples will be used Safety: Changes in gut-microbial composition will be measured in the TIM-2 model of the human colon in response to specific S\&SEs in a sub-group (UM).
Inflammation markers (adults) Up to 1 year. Safety: Change in inflammation markers will be measured by a adipose tissue biopsy (needle biopsy) in a sub-group (UM).
Glucose tolerance (adults) Up to 1 year. Efficacy: Glucose tolerance will be measured by a 7-step oral glucose tolerance test (OGTT) in a sub-study (UM).
Lipolysis (adults) Up to 1 year. Safety: Markers of lipolysis will be measured by a adipose tissue biopsy (needle biopsy) in a sub-group (UM).
Baseline and postprandial energy expenditure (adults) Up to 6 months. Efficacy: Energy expenditure will be measured in a sub-group by the ventilated hood system - a sub-study at UCPH.
Insulin sensitivity (adults) Up to 1 year. Efficacy: Insulin sensitivity will be measured by a 7-point oral glucose tolerance test (OGTT) in a sub-study (UM).
Baseline and postprandial appetite (adults) Up to 6 months. Efficacy: Appetite will be measured only in a sub-group by visual analog scales and acute energy intake - a sub-study at UCPH.
Baseline and postprandial blood samples (adults) Up to 6 months. Efficacy: Blood samples will be taken in a small group of the participants in the sub-study at UCPH.
Baseline and postprandial substrate oxidation (adults) Up to 6 months. Efficacy: The substrate oxidation will be measured only in a sub-group of adults by the ventilated hood system - a sub-study at UCPH.
Changes in gut-microbial functionality in response to S&SEs in vitro (adults) Up to 1 year. Safety: Changes in gut-microbial functionality (metabolite production) will be assessed in the TIM-2 model of the human colon in response to specific S\&SEs in a sub-group (UM).
Trial Locations
- Locations (4)
Department of Nutrition, Exercise and Sports
š©š°Frederiksberg, Denmark
University of Navarra
šŖšøPamplona, Spain
University of Maastricht
š³š±Maastricht, Netherlands
Harokopio University
š¬š·Kallithea-Athens, Greece