ObesitySWEETNCT04226911
Sweeteners and Sweetness Enhancers: Prolonged Effects on Health, Obesity and Safety
A study testing S&SEs and Sugar in people with Obesity, run by Anne Birgitte Raben at 4 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- S&SEs and Sugar
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 379 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 30 Jan 2020to 6 Oct 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 65 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Age: 18-65 years.
- BMI: ≥25.0 kg/m2 (no upper limit). For women: Use of contraceptive methods and not wishing/planning to become pregnant in the 1 year of the intervention study.
- Regular consumption of sugar-containing/sugar-sweetened products.
- Able to participate in CIDs and dietician meetings during normal working hours.
- Motivation and willingness to be randomized to any of the two groups and to do the best to follow the given protocol.
- Age: 6-12 years.
Show all 9Show fewer
- BMI-for-age: >85th percentile (no upper limit).
- Able to participate in CIDs during normal working hours.
- Motivation and willingness to be randomized to any of the two groups and to do the best to follow the given protocol.
Who cannot join
- Weight change (increase or decrease) >5% during the past 2 months prior to the study.
- Surgical treatment of obesity.
- Blood donation < 3 month prior to study.
- Change in smoking habits during the last month. Smoking is allowed provided subjects have not recently changed habits. However, smoking status is monitored throughout the study and used as a confounding variable.
- Regularly drinking >21 alcoholic units per week (men), or >14 alcoholic units/week (women).
- Intensive physical training (>10 hours of per week).
Show all 47Show fewer
- Self-reported eating disorders.
- Intolerance and allergies expected to interfere with the study.
- Self-reported drug abuse within the previous 12 months.
- Night- or shift work that ends later than 11 PM.
- 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 with national language.
- 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
- Participant's general condition contraindicates continuing the study as evaluated by the daily study manager, site-PI, PI or clinical responsible.
- Simultaneous participation in other clinical intervention studies.
- Medical conditions as known by the persons:
- Diagnosed diabetes mellitus.
- Medical history of CVD (e.g. current angina; myocardial infarction or stroke within the past 6 months; heart failure; symptomatic peripheral vascular disease).
- Systolic blood pressure above 160 mmHg and/or diastolic blood pressure above 100 mmHg (measured at screening) whether on or off treatment for hypertension.
- 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).
- Active inflammatory bowel disease, celiac disease, chronic pancreatitis or other disorder potentially causing malabsorption.
- 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 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 participation to 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 or blood pressure 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).
- Laboratory screening:
- If all of the above criteria are satisfied, the adult participant is eligible for a laboratory screening. A blood sample is collected and immediately analysed for glucose and haemoglobin concentrations (Haemocue).
- Glucose ≥ 7.0 mmol/L.
- Haemoglobin concentration below local laboratory reference values (i.e. anaemia).
- Or any other significant abnormality on these tests which in the investigators opinion may be clinically significant and require further assessment.
- After WL period (CID2, Month 2):
- Failure to reach at least 5% weight reduction during the WL period (Months 0-2). This leads to exclusion from the WM intervention
- Intensive physical training (>10 hours of per week).
- Self-reported eating disorders.
- Intolerance and allergies expected to interfere with the study.
- Insufficient communication with national language.
- 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.
- Subject's general condition contraindicates continuing the study as evaluated by the daily study manager, principal investigator or clinical responsible.
- Simultaneous participation in other clinical intervention studies.
- Medical conditions as known by the child and the representative adult:
- Diagnosed diabetes mellitus.
- Other diseases that may influence the study outcomes as evaluated by the daily study manager, site-PI, PI or clinical responsible.
- Medication:
- Use currently or within the previous 3 months of prescription or over the counter medication that has the potential of affecting body weight.
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
Denmark1 site
Department of Nutrition, Exercise and Sports
Frederiksberg, 1958
About this study
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:
Read more
- 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).
- Conditions
- Obesity
- Being tested
- S&SEs, Sugar
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S&SEsBehavioural
S\&SEs:
As many sugar-containing products in the diet as possible should be replaced with S\&SE-containing products.
To ensure that a certain amount of S\&SE products is consumed every day, a fixed minimum amount of units for each individual is planned.
SugarBehavioural
Sugar group:
In the sugar group it is allowed to consume up to a certain number of units of sugar-containing products each day, corresponding to < 10 E% added sugar.
The sugar group is not allowed to consume any S\&SE products.
| Study group | Role | What they receive |
|---|---|---|
| Sweeteners and sweetness enhancers (S&SEs) | Experimental | Healthy diet < 10 energy % (E%) sugar, foods and drinks with S\&SEs allowed. Receives: Behavioral: S&SEs |
| Sugar group | Active comparator | Healthy diet, < 10 E% sugar, foods and drinks with S\&SEs not allowed. Receives: Behavioral: Sugar |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in body weight (adults)
Efficacy: Change in body weight will be measured by a calibrated digital scale.
Measured: Up to 1 year.
Changes in gut microbiota composition (adults)
Safety: Change in gut microbiota associated with impaired health (e.g. change in microbial beta-diversity and composition) will be measured by fecal samples.
Measured: Up to 1 year.
Secondary outcomes (34)
Change in BMI-for-age z-score (children)
Efficacy: Efficacy: BMI-for-age z-score will be calculated based on the childrens weight and height using WHO AnthroPlus.
Measured: Up to 1 year.
Changes in waist and hip circumferences (adults and children)
Efficacy: Changes in waist and hip circumferences will be measured with a non-elastic tape.
Measured: Up to 1 year.
Change in body composition (adults and children)
Efficacy: Body composition will be measured using Dual X-rays. Children are not DXA scanned at UM.
Measured: Up to 1 year.
Change in blood pressure and heart rate (adults and children)
Efficacy: Change in blood pressure will be measured by an automatic device on the right arm.
Measured: Up to 1 year.
Change in glucose (adults and children)
Efficacy: Change in glucose will be measured by fasting blood samples.
Measured: Up to 1 year.
Change in hemoglobin A1c (adults and children)
Efficacy: Change in hemoglobin A1c will be measured by fasting blood samples.
Measured: Up to 1 year.
Change in alanine aminotransferase (ALT) (adults and children)
Efficacy: Change in ALT will be measured by fasting blood samples.
Measured: Up to 1 year.
Change in aspartate aminotransferase (AST) (adults and children)
Efficacy: Change in AST will be measured by fasting blood samples.
Measured: Up to 1 year.
Change in insulinemia (adults and children)
Efficacy: Change in insulinemia (insulin) will be measured by fasting blood samples.
Measured: Up to 1 year.
Change in lipidemia (adults and children)
Efficacy: Change in lipidemia (total cholesterol, high-density cholesterol, low-density cholesterol, triglycerides) will be measured by fasting blood samples.
Measured: Up to 1 year.
Change C-reactive protein (CPR) (adults and children)
Efficacy: Change in CPR will be measured by fasting blood samples.
Measured: Up to 1 year.
Allergenicity by serum immunoglobulin level (adults and children)
Safety: To assess allergenicity serum immunoglobulin levels will be measured by fasting blood samples.
Measured: Up to 1 year.
Allergenicity by a skin prick test (adults)
Safety: To assess allergenicity a skin prick test will be performed.
Measured: Up to 1 year.
Allergenicity by a questionnaire (adults and children)
Safety: To assess allergenicity a questionnaire will be completed.
Measured: Up to 1 year.
Concomitant medication (adults and children)
Safety: Concomitant medication will be reported in a case report from designed for the purpose.
Measured: Up to 1 year.
Adverse events (adults and children)
Safety: Adverse events will be reported in a case report form designed for the purpose e.g. headache, constipation ect.
Measured: Up to 1 year.
Change in liver fat and lipid composition (adults)
Safety: Change in liver fat and lipid composition will be measured by magnet resonans (MR) scans in a sub-group (UM).
Measured: Up to 1 year.
Change in ghrelin (adults)
Efficacy: Change in ghrelin will be measured in a sub-group by fasting blood samples (UCPH, UM).
Measured: Up to 1 year.
Change in cholecystokinin (adults)
Efficacy: Change in cholecystokinin will be measured in a sub-group by fasting blood samples (UCPH, UM).
Measured: Up to 1 year.
Change in glucagon-like peptide-1 (GLP-1) (adults)
Efficacy: Change in GLP-1 will be measured in a sub-group by fasting blood samples (UCPH, UM).
Measured: Up to 1 year.
Change in FGF21 (adults)
Efficacy: Change in FGF21 will be measured in a sub-group by fasting blood samples (UCPH).
Measured: Up to 1 year.
Changes in gut microbiota composition (children)
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)
Measured: Up to 1 year.
Markers of adipogenesis (adults)
Safety: Markers of adipogenesis will be measured by a adipose tissue biopsy (needle biopsy) in a sub-group (UM).
Measured: Up to 1 year.
Lipolysis (adults)
Safety: Markers of lipolysis will be measured by a adipose tissue biopsy (needle biopsy) in a sub-group (UM).
Measured: Up to 1 year.
Fat cell size (adults)
Safety: Change in fat cell size will be measured by a adipose tissue biopsy (needle biopsy) in a sub-group (UM).
Measured: Up to 1 year.
Inflammation markers (adults)
Safety: Change in inflammation markers will be measured by a adipose tissue biopsy (needle biopsy) in a sub-group (UM).
Measured: Up to 1 year.
Insulin sensitivity (adults)
Efficacy: Insulin sensitivity will be measured by a 7-point oral glucose tolerance test (OGTT) in a sub-study (UM).
Measured: Up to 1 year.
Glucose tolerance (adults)
Efficacy: Glucose tolerance will be measured by a 7-step oral glucose tolerance test (OGTT) in a sub-study (UM).
Measured: Up to 1 year.
Changes in gut-microbial composition in response to specific S&SEs in vitro (adults)
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).
Measured: Only baseline feces samples will be used
Changes in gut-microbial functionality in response to S&SEs in vitro (adults)
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).
Measured: Up to 1 year.
Baseline and postprandial energy expenditure (adults)
Efficacy: Energy expenditure will be measured in a sub-group by the ventilated hood system - a sub-study at UCPH.
Measured: Up to 6 months.
Baseline and postprandial substrate oxidation (adults)
Efficacy: The substrate oxidation will be measured only in a sub-group of adults by the ventilated hood system - a sub-study at UCPH.
Measured: Up to 6 months.
Baseline and postprandial appetite (adults)
Efficacy: Appetite will be measured only in a sub-group by visual analog scales and acute energy intake - a sub-study at UCPH.
Measured: Up to 6 months.
Baseline and postprandial blood samples (adults)
Efficacy: Blood samples will be taken in a small group of the participants in the sub-study at UCPH.
Measured: Up to 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2020
- Study start30 Jan 2020
- Primary completion6 Oct 2022
- Study completion6 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 379 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anne Birgitte Raben
- Sponsor type
- University, hospital or other
- Collaborators
- Harokopio University, University of Navarra, University of Liverpool, Maastricht University, University of Leeds, Wageningen University, European Clinical Research Infrastructure Network, University of Surrey, Bioiatriki Idiotiko Polyiatreio Iatpikh Anonymos Etairia, NetUnion SARL, Pectolite GMBH
- Responsible party
- Sponsor-investigator, Anne Birgitte Raben, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04226911
- Sponsor's protocol ID
- SWEET WP3
- Acronym
- SWEET
- Status last verified
- Oct 2022
- First submitted
- 18 Dec 2019
- Last updated
- 1 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All data will be collected in a central DataHub at University of Copenhagen. First, the pseudo-anonymised individual participant data (IPD) are to be shared between (WP3-) relevant SWEET partners within the SWEET consortium via a data processor agreement (DPA). Second, the pseudo-anonymised IPD will be made available upon request before 2032 via a data sharing contract. Third, from 2032 (10 years after LPLV) fully anonymised data can be transferred."
Publications
Pang MD, Bastings JJAJ, Jocken JWE, Harrold JA, Halford JCG, Kjolbaek L, Raben A, Adam TCM, Blaak EE, Goossens GH; SWEET consortium. Long-term effect of sweeteners and sweetness enhancers on gene expression markers of adipose tissue function, adipocyte morphology, and metabolic health: a SWEET substudy. Int J Obes (Lond). 2026 Jun 2. doi: 10.1038/s41366-026-02117-z. Online ahead of print.
PubMed 42230988Pang MD, Kjolbaek L, Bastings JJAJ, Andersen SSH, Umanets A, Sost MM, Navas-Carretero S, Reppas K, Finlayson G, Hodgkins CE, Del Alamo M, Lam T, Moshoyiannis H, Feskens EJM, Adam TCM, Goossens GH, Halford JCG, Harrold JA, Manios Y, Martinez JA, Blaak EE, Raben A. Effect of sweeteners and sweetness enhancers on weight management and gut microbiota composition in individuals with overweight or obesity: the SWEET study. Nat Metab. 2025 Oct;7(10):2083-2098. doi: 10.1038/s42255-025-01381-z. Epub 2025 Oct 7.
PubMed 41057614Pang MD, Bastings JJAJ, Op den Kamp-Bruls YMH, Harrold JA, Kjolbaek L, Halford JCG, Adam TCM, Raben A, Schrauwen-Hinderling VB, Goossens GH, Blaak EE. The effect of weight loss on whole-body and tissue-specific insulin sensitivity and hepatic lipid content and composition: SWEET substudy. Obesity (Silver Spring). 2023 Jul;31(7):1745-1754. doi: 10.1002/oby.23773.
PubMed 37368517Kjolbaek L, Manios Y, Blaak EE, Martinez JA, Feskens EJM, Finlayson G, Andersen SSH, Reppas K, Navas-Carretero S, Adam TC, Hodgkins CE, Del Alamo M, Lam T, Moshoyiannis H, Halford JCG, Harrold JA, Raben A. Protocol for a multicentre, parallel, randomised, controlled trial on the effect of sweeteners and sweetness enhancers on health, obesity and safety in overweight adults and children: the SWEET project. BMJ Open. 2022 Oct 12;12(10):e061075. doi: 10.1136/bmjopen-2022-061075.
PubMed 36223962
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sweeteners and Sweetness Enhancers: Prolonged Effects on Health, Obesity and Safety
- ClinicalTrials.gov ID
- NCT04226911
- Acronym / sponsor ID
- SWEET / SWEET WP3
- Conditions
- Obesity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 379 participants (actual)
- Lead sponsor
- Anne Birgitte RabenUniversity, hospital or other
- Collaborators
- Harokopio University, University of Navarra, University of Liverpool, Maastricht University, University of Leeds, Wageningen University, European Clinical Research Infrastructure Network, University of Surrey, Bioiatriki Idiotiko Polyiatreio Iatpikh Anonymos Etairia, NetUnion SARL, Pectolite GMBH
- Study start
- 30 Jan 2020 (actual)
- Primary completion
- 6 Oct 2022 (actual)
- Study completion
- 6 Oct 2022 (actual)
- First posted
- 13 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sweeteners and sweetness enhancers (S&SEs) | Experimental | Behavioral: S&SEsHealthy diet < 10 energy % (E%) sugar, foods and drinks with S\&SEs allowed. |
| Sugar group | Active comparator | Behavioral: SugarHealthy diet, < 10 E% sugar, foods and drinks with S\&SEs not allowed. |
Who may qualify
- Ages
- 6 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Age: 18-65 years.
- BMI: ≥25.0 kg/m2 (no upper limit). For women: Use of contraceptive methods and not wishing/planning to become pregnant in the 1 year of the intervention study.
- Regular consumption of sugar-containing/sugar-sweetened products.
- Able to participate in CIDs and dietician meetings during normal working hours.
- Motivation and willingness to be randomized to any of the two groups and to do the best to follow the given protocol.
Key exclusion criteria (47 listed)
- Weight change (increase or decrease) >5% during the past 2 months prior to the study.
- Surgical treatment of obesity.
- Blood donation < 3 month prior to study.
- Change in smoking habits during the last month. Smoking is allowed provided subjects have not recently changed habits. However, smoking status is monitored throughout the study and used as a confounding variable.
- Regularly drinking >21 alcoholic units per week (men), or >14 alcoholic units/week (women).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| S&SEsS\&SEs: As many sugar-containing products in the diet as possible should be replaced with S\&SE-containing products. To ensure that a certain amount of S\&SE products is consumed every day, a fixed minimum amount of units for each individual is planned. | Behavioural | Sweeteners and sweetness enhancers (S&SEs) |
| SugarSugar group: In the sugar group it is allowed to consume up to a certain number of units of sugar-containing products each day, corresponding to < 10 E% added sugar. The sugar group is not allowed to consume any S\&SE products. | Behavioural | Sugar group |
Primary outcome
Change in body weight (adults)
Time frame: Up to 1 year.
Efficacy: Change in body weight will be measured by a calibrated digital scale.
Changes in gut microbiota composition (adults)
Time frame: 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.
34 secondary outcomes
Change in BMI-for-age z-score (children)
Time frame: Up to 1 year.
Changes in waist and hip circumferences (adults and children)
Time frame: Up to 1 year.
Change in body composition (adults and children)
Time frame: Up to 1 year.
Change in blood pressure and heart rate (adults and children)
Time frame: Up to 1 year.
Change in glucose (adults and children)
Time frame: Up to 1 year.
Change in hemoglobin A1c (adults and children)
Time frame: Up to 1 year.
Change in alanine aminotransferase (ALT) (adults and children)
Time frame: Up to 1 year.
Change in aspartate aminotransferase (AST) (adults and children)
Time frame: Up to 1 year.
Change in insulinemia (adults and children)
Time frame: Up to 1 year.
Change in lipidemia (adults and children)
Time frame: Up to 1 year.
Change C-reactive protein (CPR) (adults and children)
Time frame: Up to 1 year.
Allergenicity by serum immunoglobulin level (adults and children)
Time frame: Up to 1 year.
Allergenicity by a skin prick test (adults)
Time frame: Up to 1 year.
Allergenicity by a questionnaire (adults and children)
Time frame: Up to 1 year.
Concomitant medication (adults and children)
Time frame: Up to 1 year.
Adverse events (adults and children)
Time frame: Up to 1 year.
Change in liver fat and lipid composition (adults)
Time frame: Up to 1 year.
Change in ghrelin (adults)
Time frame: Up to 1 year.
Change in cholecystokinin (adults)
Time frame: Up to 1 year.
Change in glucagon-like peptide-1 (GLP-1) (adults)
Time frame: Up to 1 year.
Change in FGF21 (adults)
Time frame: Up to 1 year.
Changes in gut microbiota composition (children)
Time frame: Up to 1 year.
Markers of adipogenesis (adults)
Time frame: Up to 1 year.
Lipolysis (adults)
Time frame: Up to 1 year.
Fat cell size (adults)
Time frame: Up to 1 year.
Inflammation markers (adults)
Time frame: Up to 1 year.
Insulin sensitivity (adults)
Time frame: Up to 1 year.
Glucose tolerance (adults)
Time frame: Up to 1 year.
Changes in gut-microbial composition in response to specific S&SEs in vitro (adults)
Time frame: Only baseline feces samples will be used
Changes in gut-microbial functionality in response to S&SEs in vitro (adults)
Time frame: Up to 1 year.
Baseline and postprandial energy expenditure (adults)
Time frame: Up to 6 months.
Baseline and postprandial substrate oxidation (adults)
Time frame: Up to 6 months.
Baseline and postprandial appetite (adults)
Time frame: Up to 6 months.
Baseline and postprandial blood samples (adults)
Time frame: Up to 6 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2022.
- Derived from this study: PubMed 42230988Pang MD, Bastings JJAJ, Jocken JWE, Harrold JA, Halford JCG, Kjolbaek L, Raben A, Adam TCM, Blaak EE, Goossens GH; SWEET consortium. Long-term effect of sweeteners and sweetness enhancers on gene expression markers of adipose tissue function, adipocyte morphology, and metabolic health: a SWEET substudy. Int J Obes (Lond). 2026 Jun 2. doi: 10.1038/s41366-026-02117-z. Online ahead of print.
- Derived from this study: PubMed 41057614Pang MD, Kjolbaek L, Bastings JJAJ, Andersen SSH, Umanets A, Sost MM, Navas-Carretero S, Reppas K, Finlayson G, Hodgkins CE, Del Alamo M, Lam T, Moshoyiannis H, Feskens EJM, Adam TCM, Goossens GH, Halford JCG, Harrold JA, Manios Y, Martinez JA, Blaak EE, Raben A. Effect of sweeteners and sweetness enhancers on weight management and gut microbiota composition in individuals with overweight or obesity: the SWEET study. Nat Metab. 2025 Oct;7(10):2083-2098. doi: 10.1038/s42255-025-01381-z. Epub 2025 Oct 7.
- Derived from this study: PubMed 37368517Pang MD, Bastings JJAJ, Op den Kamp-Bruls YMH, Harrold JA, Kjolbaek L, Halford JCG, Adam TCM, Raben A, Schrauwen-Hinderling VB, Goossens GH, Blaak EE. The effect of weight loss on whole-body and tissue-specific insulin sensitivity and hepatic lipid content and composition: SWEET substudy. Obesity (Silver Spring). 2023 Jul;31(7):1745-1754. doi: 10.1002/oby.23773.
- Derived from this study: PubMed 36223962Kjolbaek L, Manios Y, Blaak EE, Martinez JA, Feskens EJM, Finlayson G, Andersen SSH, Reppas K, Navas-Carretero S, Adam TC, Hodgkins CE, Del Alamo M, Lam T, Moshoyiannis H, Halford JCG, Harrold JA, Raben A. Protocol for a multicentre, parallel, randomised, controlled trial on the effect of sweeteners and sweetness enhancers on health, obesity and safety in overweight adults and children: the SWEET project. BMJ Open. 2022 Oct 12;12(10):e061075. doi: 10.1136/bmjopen-2022-061075.
- Individual participant dataSharing planned: Yes. All data will be collected in a central DataHub at University of Copenhagen. First, the pseudo-anonymised individual participant data (IPD) are to be shared between (WP3-) relevant SWEET partners within the SWEET consortium via a data processor agreement (DPA). Second, the pseudo-anonymised IPD will be made available upon request before 2032 via a data sharing contract. Third, from 2032 (10 years after LPLV) fully anonymised data can be transferred."
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing S&SEs and Sugar in people with Obesity, run by Anne Birgitte Raben at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Denmark, Greece, Netherlands, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in body weight (adults) (time frame: Up to 1 year.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04226911, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2022.