Healthy AdultNCT07361406
SweetSpot - The Effect of Non-nutritive Sweeteners on Health
A study testing Diet with non-nutritive sweeteners and Diet without non-nutritive sweeteners in people with Healthy Adult, run by Wageningen University at 1 site in Netherlands.
Trial summary
The aim of the study is to investigate the effect of non-nutritive sweeteners on glucose regulation. Secondary objectives are to investigate the effect of NNS on gut microbiome, gut hormone secretion, sweet taste sensitivity and preference, and the excretion of NNS in urine. Read more about this study
- Who is it for?
- Ages 45 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Adult
- What is being tested?
- Diet with non-nutritive sweeteners and Diet without non-nutritive sweeteners
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteNetherlands
- Study dates
- 23 Feb 2026to 26 Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 45 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 45-79 years;
- BMI of 20-35 kg/m2;
- Having veins suitable for placement of a venflon catheter.
Who cannot join
- Diseases or prior surgeries affecting the stomach, liver, kidneys or intestines (allowed i.e. appendectomy);
- Cardiovascular diseases (e.g. heart failure) or cancer (e.g. non-invasive skin cancer allowed);
- Diagnosed with type 1 or type 2 diabetes;
- Drug treated thyroid diseases (well substituted hypothyroidism is allowed for inclusion);
- HbA1c level >6.5% (>48 mmol/mol), as measured during the screening visit;
- Anaemia defined as Hb concentrations <8.5 mmol/L for men and <7.5 mmol/L for women via finger prick;
Show all 24Show fewer
- Regular use of/receiving medication interfering with research outcomes (as judged by research physician), such as use of glucose lowering drugs, insulin, or use of medication that impacts the gastro-intestinal system;
- Use of antibiotics over the last 3 months before study start;
- Donated blood within 2 months prior to the screening;
- Food allergies, intolerances (including lactose/gluten intolerance) for products used in the study design and/or dietary restrictions interfering with the study (including special diets and eating disorders);
- Followed a diet that can interfere with the study outcomes within 1 month prior to the screening (e.g. ketogenic, sugar free, carbohydrate free);
- Not willing to eat all products in the study diet, including eggs and dairy. Vegetarian is possible;
- Not willing to consume non-nutritive sweeteners;
- Not willing to quit the use of supplements that can interfere with the study outcomes (e.g. pre- or probiotics).
- Intention to change the intensity of exercise during the study period or planning to join a intensive sport event (e.g. marathon or triathlon);
- Intention to lose or gain weight;
- Working night shifts regularly;
- Smoking regularly
- Use of soft and/or hard drugs (cannabis included);
- Abuse of alcohol (defined as >14 glasses (women) or >21 glasses (men) of alcoholic beverages per week);
- Being pregnant or lactating or planning to become pregnant;
- Inability to understand study information and/or communicate with staff;
- Participation in another study that involves an intervention within two months prior to the intervention;
- Working or doing a thesis/internship at the division of Human Nutrition \& Health, or the Food, Health \& Consumer Research group of Wageningen Food \& Biobased Research.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Wageningen University & Research
Wageningen, Gelderland, 6708WG
About this study
Official title: SweetSpot - The Effect of Non-nutritive Sweeteners on Glucose Regulation, Gut Microbiome, and Gut Hormone Secretion in Healthy Adults: a Fully Controlled Cross-over Intervention Study
The aim of the study is to investigate the effect of non-nutritive sweeteners on glucose regulation. Secondary objectives are to investigate the effect of NNS on gut microbiome, gut hormone secretion, sweet taste sensitivity and preference, and the excretion of NNS in urine.
Read the detailed description
Sugar intake has increased over the years, simultaneously with the prevalence of overweight and obesity. To decrease sugar intake, consumption of non-nutritive sweeteners (NNS) has increased and opinions on its use remain divided. A fully controlled dietary intervention using a NNS mixture and dose that is similar to real-life intake, is therefore necessary to advance our understanding of the potential effects of NNS on glucose regulation, gut microbiome, and gut hormone secretion under real-life conditions.
The aim of this study is to investigate the effect of non-nutritive sweeteners on glucose regulation. Secondary objectives are to investigate the effect of NNS on gut microbiome, gut hormone secretion, sweet taste sensitivity and preference, and the excretion of NNS in urine.
To do this, a single blind, fully controlled dietary intervention with a cross-over design will be performed. The study will consist of 2x8 weeks of intervention, with a washout of > 6 weeks in between. The study population will be 60 healthy adults aged 45-79, with a BMI between 20-35 kg/m2.
The study will consist of a fully controlled diet of two 8-week intervention periods (2 weeks run-in + 6 weeks intervention). The diets differ in the presence of non-nutritive sweeteners (NNS): NNS-diet versus non-NNS diet, where additional NNS are added to the NNS-diet.
The primary outcome measure will be the within person difference in blood glucose incremental area under the curve following a 75 g glucose tolerance test between the NNS diet and the non-NNS diet. Secondary outcome measures are the effect of NNS on Matsuda index, insulin response, blood lipid profile, and gut hormone secretion will be determined. The effect of NNS on small- and large intestinal microbiome will be investigated by a change in composition, functionality, and short chain fatty acid content. The effect of NNS on sweet taste sensitivity, preference, and liking will be investigated, as well as the excretion of NNS in urine and saliva.
The total time invested by participants is around 85 hours. Participants are restricted for 16 weeks in their eating habits, since they follow a fully controlled diet prepared by the research facility. Participants will visit the research facility in total 38 times. In total, ~ 603 mL of blood will be drawn by experienced nurses over the entire RCT (>6 month period). During DEXA scans, participants will receive a total of about 0.006 mSv of radiation.
Invasive measurements that participants can experience as burden are collection of faecal and urine samples, and finding back the Simba capsules in the stool. Non-invasive measurements for participants are wearing the CGM, wearing the ActiGraph, consuming the blue cakes, and performing sensory tests.
- Conditions
- Healthy Adult
- Being tested
- Diet with non-nutritive sweeteners, Diet without non-nutritive sweeteners
- Keywords
- glucose metabolism, gut microbiome, gut hormones, non-nutritive sweeteners
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diet with non-nutritive sweetenersOther
Fully controlled diet with added mixture of non-nutritive sweeteners. The mixture consist of 6 different non-nutritive sweeteners: acesulfame-K, aspartame, cyclamate, saccharin, sucralose, and rebaudioside A (stevia).
Diet without non-nutritive sweetenersOther
Fully controlled diet without any non-nutritive sweeteners added.
| Study group | Role | What they receive |
|---|---|---|
| NNS / no-NNS | Other | In this arm, participants will first receive the NNS diet, and the no-NNS diet in the second study period. Receives: Other: Diet with non-nutritive sweeteners; Other: Diet without non-nutritive sweeteners |
| No-NNS / NNS | Other | In this arm, participants will first receive the no-NNS diet, and the NNS diet in the second study period. Receives: Other: Diet with non-nutritive sweeteners; Other: Diet without non-nutritive sweeteners |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in change in 2h iAUC glucose after 6 weeks between the intervention and the control.
The primary outcome measure is the difference in change in iAUC of blood glucose levels following a 2-hour oral glucose tolerance test (OGTT) after six weeks between the intervention period and the control period.
Measured: Week 2 and week 8 in both intervention periods (4 times in total)
Secondary outcomes (19)
Matsuda index
Matsuda index after an OGTT
Measured: Week 2 and week 8 in both intervention periods (4 times in total)
Fasting blood glucose
Fasting blood glucose
Measured: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Fasting blood insulin
Fasting blood insulin
Measured: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Postprandial insulin response
2-hour iAUC blood insulin during OGTT
Measured: Week 2 and 8 in both intervention periods (4 times in total).
Postprandial glucose response after a breakfast
Postprandial blood glucose responses (PPGR) following specific meals measured by CGM.
Measured: Week 7 in both study periods (2 times in total)
Blood lipid profile
All circulating blood lipids, including all cholesterol types, triglycerides, and free fatty acids (FFAs).
Measured: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Gut microbiota composition
Microbiota composition in faeces
Measured: Average of three samples per timepoint. Measured at baseline & 2 times per intervention period (week 2 and week 8). 15 samples over 5 timepoints in total.
Gut microbiota function
Microbiota functionality measured in faeces
Measured: Average of three samples per timepoint. Measured at baseline & 2 times per intervention period (week 2 and week 8). 15 samples over 5 timepoints in total.
Microbial metabolites
Microbial metabolites measured in faeces
Measured: Average of three samples per timepoint. Measured at baseline & 2 times per intervention period (week 2 and week 8). 15 samples over 5 timepoints in total.
Small intestinal microbiota composition
Microbiota composition of the small intestine measured with Simba Capsules
Measured: Week 7 of both intervention periods (2 times in total).
Gastro-intestinal transit time
Gastro-intestinal transit time measured with blue muffins.
Measured: Baseline & week 7 of both intervention periods (3 times in total).
Oral microbiome composition & function
Oral microbiome composition \& function measured in saliva
Measured: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Postprandial GLP-1 secretion
3-hour AUC of GLP-1 during an OGTT.
Measured: Week 2 and 8 of both intervention periods (4 times in total).
Postprandial GIP secretion
3-hour AUC of GIP during an OGTT.
Measured: Week 2 and 8 of both intervention periods (4 times in total).
Sweetness-liker phenotype
Sweetness-liker phenotype, with the sweetness liker test.
Measured: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Sweetness preference & liking
Sweetness preference \& liking measured on a rank-rating scale. Preference will be determined using the categorical values from the rank-rating scale (1-5), and liking will be determined using the continuous values from the rank-rating scale (0-100).
Measured: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Sweet taste sensitivity
Sweet taste sensitivity measured on a 100mm Visual Analogue Scale. A higher score for all solutions indicates a higher sweet taste sensitivity.
Measured: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Excretion of NNS in urine
Excretion of NNS in urine
Measured: Baseline, week 2 and week 8 in intervention period 1, and every two weeks in intervention period 2 (7 times in total).
Excretion of NNS in saliva
Excretion of NNS in saliva
Measured: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2026
- Study start23 Feb 2026
- Primary completion26 Mar 2027 (estimated)
- Study completion26 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy AdultStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wageningen University
- Sponsor type
- University, hospital or other
- Collaborators
- Food & Biobased Research - Wageningen UR, TKI Agri & Food, The Magnum Ice Cream Company, Tate & Lyle, Symrise AG, American Beverage Association, Yildiz Holding
- Responsible party
- Principal investigator, Monica Mars, Wageningen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07361406
- Sponsor's protocol ID
- NL010297
- Status last verified
- Nov 2026
- First submitted
- 13 Jan 2026
- Last updated
- 6 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SweetSpot - The Effect of Non-nutritive Sweeteners on Glucose Regulation, Gut Microbiome, and Gut Hormone Secretion in Healthy Adults: a Fully Controlled Cross-over Intervention Study
- ClinicalTrials.gov ID
- NCT07361406
- Acronym / sponsor ID
- NL010297
- Conditions
- Healthy Adult
- Keywords
- glucose metabolism, gut microbiome, gut hormones, non-nutritive sweeteners
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Wageningen UniversityUniversity, hospital or other
- Collaborators
- Food & Biobased Research - Wageningen UR, TKI Agri & Food, The Magnum Ice Cream Company, Tate & Lyle, Symrise AG, American Beverage Association, Yildiz Holding
- Study start
- 23 Feb 2026 (actual)
- Primary completion
- 26 Mar 2027 (estimated)
- Study completion
- 26 Mar 2027 (estimated)
- First posted
- 23 Jan 2026 (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 the study is to investigate the effect of non-nutritive sweeteners on glucose regulation. Secondary objectives are to investigate the effect of NNS on gut microbiome, gut hormone secretion, sweet taste sensitivity and preference, and the excretion of NNS in urine.
Detailed description
Sugar intake has increased over the years, simultaneously with the prevalence of overweight and obesity. To decrease sugar intake, consumption of non-nutritive sweeteners (NNS) has increased and opinions on its use remain divided. A fully controlled dietary intervention using a NNS mixture and dose that is similar to real-life intake, is therefore necessary to advance our understanding of the potential effects of NNS on glucose regulation, gut microbiome, and gut hormone secretion under real-life conditions.
The aim of this study is to investigate the effect of non-nutritive sweeteners on glucose regulation. Secondary objectives are to investigate the effect of NNS on gut microbiome, gut hormone secretion, sweet taste sensitivity and preference, and the excretion of NNS in urine.
To do this, a single blind, fully controlled dietary intervention with a cross-over design will be performed. The study will consist of 2x8 weeks of intervention, with a washout of > 6 weeks in between. The study population will be 60 healthy adults aged 45-79, with a BMI between 20-35 kg/m2.
The study will consist of a fully controlled diet of two 8-week intervention periods (2 weeks run-in + 6 weeks intervention). The diets differ in the presence of non-nutritive sweeteners (NNS): NNS-diet versus non-NNS diet, where additional NNS are added to the NNS-diet.
The primary outcome measure will be the within person difference in blood glucose incremental area under the curve following a 75 g glucose tolerance test between the NNS diet and the non-NNS diet. Secondary outcome measures are the effect of NNS on Matsuda index, insulin response, blood lipid profile, and gut hormone secretion will be determined. The effect of NNS on small- and large intestinal microbiome will be investigated by a change in composition, functionality, and short chain fatty acid content. The effect of NNS on sweet taste sensitivity, preference, and liking will be investigated, as well as the excretion of NNS in urine and saliva.
The total time invested by participants is around 85 hours. Participants are restricted for 16 weeks in their eating habits, since they follow a fully controlled diet prepared by the research facility. Participants will visit the research facility in total 38 times. In total, ~ 603 mL of blood will be drawn by experienced nurses over the entire RCT (>6 month period). During DEXA scans, participants will receive a total of about 0.006 mSv of radiation.
Invasive measurements that participants can experience as burden are collection of faecal and urine samples, and finding back the Simba capsules in the stool. Non-invasive measurements for participants are wearing the CGM, wearing the ActiGraph, consuming the blue cakes, and performing sensory tests.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NNS / no-NNS | Other | Other: Diet with non-nutritive sweeteners, Other: Diet without non-nutritive sweetenersIn this arm, participants will first receive the NNS diet, and the no-NNS diet in the second study period. |
| No-NNS / NNS | Other | Other: Diet with non-nutritive sweeteners, Other: Diet without non-nutritive sweetenersIn this arm, participants will first receive the no-NNS diet, and the NNS diet in the second study period. |
Who may qualify
- Ages
- 45 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 45-79 years;
- BMI of 20-35 kg/m2;
- Having veins suitable for placement of a venflon catheter.
Key exclusion criteria (24 listed)
- Diseases or prior surgeries affecting the stomach, liver, kidneys or intestines (allowed i.e. appendectomy);
- Cardiovascular diseases (e.g. heart failure) or cancer (e.g. non-invasive skin cancer allowed);
- Diagnosed with type 1 or type 2 diabetes;
- Drug treated thyroid diseases (well substituted hypothyroidism is allowed for inclusion);
- HbA1c level >6.5% (>48 mmol/mol), as measured during the screening visit;
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 |
|---|---|---|
| Diet with non-nutritive sweetenersFully controlled diet with added mixture of non-nutritive sweeteners. The mixture consist of 6 different non-nutritive sweeteners: acesulfame-K, aspartame, cyclamate, saccharin, sucralose, and rebaudioside A (stevia). | Other | NNS / no-NNS, No-NNS / NNS |
| Diet without non-nutritive sweetenersFully controlled diet without any non-nutritive sweeteners added. | Other | NNS / no-NNS, No-NNS / NNS |
Primary outcome
Difference in change in 2h iAUC glucose after 6 weeks between the intervention and the control.
Time frame: Week 2 and week 8 in both intervention periods (4 times in total)
The primary outcome measure is the difference in change in iAUC of blood glucose levels following a 2-hour oral glucose tolerance test (OGTT) after six weeks between the intervention period and the control period.
19 secondary outcomes
Matsuda index
Time frame: Week 2 and week 8 in both intervention periods (4 times in total)
Fasting blood glucose
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Fasting blood insulin
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Postprandial insulin response
Time frame: Week 2 and 8 in both intervention periods (4 times in total).
Postprandial glucose response after a breakfast
Time frame: Week 7 in both study periods (2 times in total)
Blood lipid profile
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Gut microbiota composition
Time frame: Average of three samples per timepoint. Measured at baseline & 2 times per intervention period (week 2 and week 8). 15 samples over 5 timepoints in total.
Gut microbiota function
Time frame: Average of three samples per timepoint. Measured at baseline & 2 times per intervention period (week 2 and week 8). 15 samples over 5 timepoints in total.
Microbial metabolites
Time frame: Average of three samples per timepoint. Measured at baseline & 2 times per intervention period (week 2 and week 8). 15 samples over 5 timepoints in total.
Small intestinal microbiota composition
Time frame: Week 7 of both intervention periods (2 times in total).
Gastro-intestinal transit time
Time frame: Baseline & week 7 of both intervention periods (3 times in total).
Oral microbiome composition & function
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Postprandial GLP-1 secretion
Time frame: Week 2 and 8 of both intervention periods (4 times in total).
Postprandial GIP secretion
Time frame: Week 2 and 8 of both intervention periods (4 times in total).
Sweetness-liker phenotype
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Sweetness preference & liking
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Sweet taste sensitivity
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Excretion of NNS in urine
Time frame: Baseline, week 2 and week 8 in intervention period 1, and every two weeks in intervention period 2 (7 times in total).
Excretion of NNS in saliva
Time frame: Baseline & 2 times per intervention period (week 2 and week 8). 5 times in total.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Diet with non-nutritive sweeteners and Diet without non-nutritive sweeteners in people with Healthy Adult, run by Wageningen University at 1 site in Netherlands.
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 3 inclusion and 24 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: under way, not looking for participants, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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?
This study is still under way. Results are not available in the source record yet.
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?
Difference in change in 2h iAUC glucose after 6 weeks between the intervention and the control. (time frame: Week 2 and week 8 in both intervention periods (4 times in total)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Nov 2026.