Prediabetic StateSweetheartNCT07377097
Effects of Sweetener Consumption on Risk Factors for Heart Disease in Prediabetic Subjects
A study testing Saccharin, Sucralose and Erythritol in people with Prediabetic State and Metabolic Syndrome, run by Charite University, Berlin, Germany.
Trial summary
The aim of this prospective interventional study is to investigate the metabolic effects of consuming artificial and natural sweeteners in persons with prediabetes. Prediabetes is a condition characterized by blood sugar levels that are elevated above normal but not yet meeting the criteria for type 2 diabetes. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Prediabetic State, Metabolic Syndrome, Insulin Resistance
- What is being tested?
- Saccharin, Sucralose and Erythritol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- No sites listed yet
- Study dates
- 5 Jan 2026to 1 Nov 2026
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Presence of prediabetes (HbA1c 5.7-6.4% or glucose after oral glucose tolerance test 140 to 199 mg/dL)
- Written informed consent available
Who cannot join
- Inability to communicate sufficiently in the required language
- Dementia or other significantly cognitively impairing condition
- Current pregnancy or breastfeeding
- Other severe internal, neurological, or psychiatric condition
- History of gout
- History of gallstones / diagnosis of cholelithiasis
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Effects of Sweetener Consumption on Risk Factors for Heart Disease
The aim of this prospective interventional study is to investigate the metabolic effects of consuming artificial and natural sweeteners in persons with prediabetes. Prediabetes is a condition characterized by blood sugar levels that are elevated above normal but not yet meeting the criteria for type 2 diabetes. This condition markedly increases the risk of progressing to type 2 diabetes, which in turn can lead to complications including cardiovascular diseases.
Artificial sweeteners such as saccharin and sucralose, as well as natural sugar substitutes like erythritol, are increasingly used as alternatives to sugar and are recommended for individuals at cardiometabolic risk - including overweight individuals, patients with prediabetes, or diabetics - to help reduce caloric intake. Recent literature has reported possible negative associations between artificial sweeteners and blood sugar regulation in healthy subjects (1). Additionally, effects on various blood cells have been observed. For example, erythritol has been shown to alter platelet function leading to increased reactivity in healthy study participants following consumption (2).
Read more
However, the impact of alternative sweeteners on metabolic processes and their effects on blood coagulation in patients with prediabetes-a population at increased risk-has not been systematically studied. In this planned interventional study, 80 patients meeting laboratory criteria for prediabetes will be randomly assigned to one of four groups, each receiving a different intervention for two weeks: saccharin, sucralose, erythritol, or a control group receiving water. The doses reflect the acceptable daily intake or known doses that are considered safe.
After enrollment, participants will visit the study center 2 times: before starting the intervention and after completing the intervention. During these visits, biological samples such as blood, urine, and stool will be collected to study metabolism, gut bacteria, immune and blood cell function. Tests will include an oral glucose tolerance test, coagulation tests, and additional blood analyses. Additionally, participants will wear a glucose monitor to track blood sugar fluctuations during the intervention.
The investigators hypothesize that consumption of alternative sweeteners negatively affects blood sugar regulation and insulin sensitivity in patients with prediabetes. Furthermore, this study will explore how the candidate sweeteners influence the gut microbiome, blood cells and other metabolic factors in this population.
- Conditions
- Prediabetic State, Metabolic Syndrome, Insulin Resistance, Thrombosis, Hypercoagulable State, Cardiovascular (CV) Risk
- Being tested
- Saccharin, Sucralose, Erythritol, Vehicle
- Medical subject headings
- Prediabetic State, Metabolic Syndrome, Insulin Resistance, Thrombosis, Thrombophilia, Cardiovascular Diseases, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SaccharinDietary supplement
Participants in the saccharin group will consume 5 mg/kg body weight of saccharin daily, dissolved in 500 mL of water. This corresponds to the maximum recommended daily intake as determined by EFSA and JECFA (the joint FAO/WHO Expert Committee on Food Additives).
SucraloseDietary supplement
Participants in the sucralose group will consume 15 mg/kg body weight of sucralose daily in 500 mL of water, representing the maximum recommended daily intake.
ErythritolDietary supplement
Those in the erythritol group will consume 0.5 g/kg body weight of erythritol daily in 500 mL of water, a dose considered safe and below levels that cause digestive discomfort (European Food Safety Authority [EFSA], 2023).
VehicleDietary supplement
Participants in the control group (vehicle) will receive a vehicle consisting of 500 mL unsweetened lemon soda
| Study group | Role | What they receive |
|---|---|---|
| Saccharin Group | Active comparator | Intervention: Saccharin Receives: Dietary Supplement: Saccharin |
| Sucralose Group | Active comparator | Intervention: Sucralose Receives: Dietary Supplement: Sucralose |
| Erythritol Group | Active comparator | Intervention: Erythritol Receives: Dietary Supplement: Erythritol |
| Control Group | Placebo comparator | Intervention: Vehicle Receives: Dietary Supplement: Vehicle |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of glucose tolerance
Measured by AUC of oral glucose tolerance test
Measured: Baseline vs. within 1 week after intervention
Secondary outcomes (9)
Change of microbiome
RNA-Sequencing of stool samples
Measured: Baseline vs. within 1 week after intervention
Flow cytometry analysis of changes in frequency of circulating monocyte subsets (%)
Measured by flow cytometry in isolated PBMCs (Peripheral Blood Mononuclear Cells) using specific antibodies with binding to CD45, CD14, CD15 and CD16 to define monocyte subsets. Values will be reported as percent of CD45+ leukocytes
Measured: Baseline vs. within 1 week after intervention
Flow cytometry analysis of changes in platelet activation marker expression (% positive platelets)
Whole blood samples will be analyzed using flow cytometry. Platelets will be detected based on size and using well-established surface markers (CD41). Activation markers will be assessed (CD62P and PAC1) and reported as percent of positive cells.
Measured: Baseline vs. within 1 week after intervention
Flow cytometry analysis of changes in platelet activation marker expression (MFI)
Whole blood samples will be analyzed using flow cytometry. Platelets will be detected based on size and using well-established surface markers (CD41). Activation markers will be assessed (CD62P and PAC1) and reported as mean fluorescence intensity.
Measured: Baseline vs. within 1 week after intervention
Changes in lipid profile
Serum analysis of Total cholesterol, HDL and LDL cholesterol, triglycerides
Measured: Baseline vs. within 1 week after intervention
Changes in blood metabolite profiles by liquid chromatography / mass spectrometry
Untargeted metabolomics analysis of plasma samples using liquid chromatography-mass spectrometry (LC/MS). Data will be reported as relative ion intensity changes from baseline (log2 fold change, mean ± SD) for significantly altered features.
Measured: Baseline vs. within 1 week after intervention
Changes in body mass index (BMI)
To observe changes in anthropometric measures. Measurement of height in meters and weight in kilograms to calculate body mass index (BMI = weight/height^2) in kg/m^2
Measured: Baseline vs. within 1 week after intervention
Changes in waist to hip ratio (WHR)
To observe changes in anthropometric measures. Measurement of waist circumference and hip circumference to calculate waist-to-hip-ratio WHR (waist circumference divided by hip circumference).
Measured: Baseline vs. within 1 week after intervention
Changes in body fat percentage
Measured by Bioelectrical Impedance Analysis (BIA)
Measured: Baseline vs. within 1 week after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2026
- Study start5 Jan 2026 (estimated)
- Primary completion1 Nov 2026 (estimated)
- Study completion1 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Prediabetic StateStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marco Witkowski, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07377097
- Sponsor's protocol ID
- Sweetheart-Study
- Acronym
- Sweetheart
- Status last verified
- Dec 2025
- First submitted
- 11 Dec 2025
- Last updated
- 29 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Witkowski M, Wilcox J, Province V, Wang Z, Nemet I, Tang WHW, Hazen SL. Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers-Brief Report. Arterioscler Thromb Vasc Biol. 2024 Sep;44(9):2136-2141. doi: 10.1161/ATVBAHA.124.321019. Epub 2024 Aug 8.
PubMed 39114916Suez J, Cohen Y, Valdes-Mas R, Mor U, Dori-Bachash M, Federici S, Zmora N, Leshem A, Heinemann M, Linevsky R, Zur M, Ben-Zeev Brik R, Bukimer A, Eliyahu-Miller S, Metz A, Fischbein R, Sharov O, Malitsky S, Itkin M, Stettner N, Harmelin A, Shapiro H, Stein-Thoeringer CK, Segal E, Elinav E. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022 Sep 1;185(18):3307-3328.e19. doi: 10.1016/j.cell.2022.07.016. Epub 2022 Aug 19.
PubMed 35987213
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Sweetener Consumption on Risk Factors for Heart Disease
- ClinicalTrials.gov ID
- NCT07377097
- Acronym / sponsor ID
- Sweetheart / Sweetheart-Study
- Conditions
- Prediabetic State, Metabolic Syndrome, Insulin Resistance, Thrombosis, Hypercoagulable State, Cardiovascular (CV) Risk
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- 5 Jan 2026 (estimated)
- Primary completion
- 1 Nov 2026 (estimated)
- Study completion
- 1 Nov 2026 (estimated)
- First posted
- 29 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 this prospective interventional study is to investigate the metabolic effects of consuming artificial and natural sweeteners in persons with prediabetes. Prediabetes is a condition characterized by blood sugar levels that are elevated above normal but not yet meeting the criteria for type 2 diabetes. This condition markedly increases the risk of progressing to type 2 diabetes, which in turn can lead to complications including cardiovascular diseases.
Artificial sweeteners such as saccharin and sucralose, as well as natural sugar substitutes like erythritol, are increasingly used as alternatives to sugar and are recommended for individuals at cardiometabolic risk - including overweight individuals, patients with prediabetes, or diabetics - to help reduce caloric intake. Recent literature has reported possible negative associations between artificial sweeteners and blood sugar regulation in healthy subjects (1). Additionally, effects on various blood cells have been observed. For example, erythritol has been shown to alter platelet function leading to increased reactivity in healthy study participants following consumption (2).
However, the impact of alternative sweeteners on metabolic processes and their effects on blood coagulation in patients with prediabetes-a population at increased risk-has not been systematically studied. In this planned interventional study, 80 patients meeting laboratory criteria for prediabetes will be randomly assigned to one of four groups, each receiving a different intervention for two weeks: saccharin, sucralose, erythritol, or a control group receiving water. The doses reflect the acceptable daily intake or known doses that are considered safe.
After enrollment, participants will visit the study center 2 times: before starting the intervention and after completing the intervention. During these visits, biological samples such as blood, urine, and stool will be collected to study metabolism, gut bacteria, immune and blood cell function. Tests will include an oral glucose tolerance test, coagulation tests, and additional blood analyses. Additionally, participants will wear a glucose monitor to track blood sugar fluctuations during the intervention.
The investigators hypothesize that consumption of alternative sweeteners negatively affects blood sugar regulation and insulin sensitivity in patients with prediabetes. Furthermore, this study will explore how the candidate sweeteners influence the gut microbiome, blood cells and other metabolic factors in this population.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Saccharin Group | Active comparator | Dietary Supplement: SaccharinIntervention: Saccharin |
| Sucralose Group | Active comparator | Dietary Supplement: SucraloseIntervention: Sucralose |
| Erythritol Group | Active comparator | Dietary Supplement: ErythritolIntervention: Erythritol |
| Control Group | Placebo comparator | Dietary Supplement: VehicleIntervention: Vehicle |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Presence of prediabetes (HbA1c 5.7-6.4% or glucose after oral glucose tolerance test 140 to 199 mg/dL)
- Written informed consent available
Key exclusion criteria (6 listed)
- Inability to communicate sufficiently in the required language
- Dementia or other significantly cognitively impairing condition
- Current pregnancy or breastfeeding
- Other severe internal, neurological, or psychiatric condition
- History of gout
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 |
|---|---|---|
| SaccharinParticipants in the saccharin group will consume 5 mg/kg body weight of saccharin daily, dissolved in 500 mL of water. This corresponds to the maximum recommended daily intake as determined by EFSA and JECFA (the joint FAO/WHO Expert Committee on Food Additives). | Dietary supplement | Saccharin Group |
| SucraloseParticipants in the sucralose group will consume 15 mg/kg body weight of sucralose daily in 500 mL of water, representing the maximum recommended daily intake. | Dietary supplement | Sucralose Group |
| ErythritolThose in the erythritol group will consume 0.5 g/kg body weight of erythritol daily in 500 mL of water, a dose considered safe and below levels that cause digestive discomfort (European Food Safety Authority [EFSA], 2023). | Dietary supplement | Erythritol Group |
| VehicleParticipants in the control group (vehicle) will receive a vehicle consisting of 500 mL unsweetened lemon soda | Dietary supplement | Control Group |
Primary outcome
Change of glucose tolerance
Time frame: Baseline vs. within 1 week after intervention
Measured by AUC of oral glucose tolerance test
9 secondary outcomes
Change of microbiome
Time frame: Baseline vs. within 1 week after intervention
Flow cytometry analysis of changes in frequency of circulating monocyte subsets (%)
Time frame: Baseline vs. within 1 week after intervention
Flow cytometry analysis of changes in platelet activation marker expression (% positive platelets)
Time frame: Baseline vs. within 1 week after intervention
Flow cytometry analysis of changes in platelet activation marker expression (MFI)
Time frame: Baseline vs. within 1 week after intervention
Changes in lipid profile
Time frame: Baseline vs. within 1 week after intervention
Changes in blood metabolite profiles by liquid chromatography / mass spectrometry
Time frame: Baseline vs. within 1 week after intervention
Changes in body mass index (BMI)
Time frame: Baseline vs. within 1 week after intervention
Changes in waist to hip ratio (WHR)
Time frame: Baseline vs. within 1 week after intervention
Changes in body fat percentage
Time frame: Baseline vs. within 1 week after intervention
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 29 Jan 2026.
- Background: PubMed 39114916Witkowski M, Wilcox J, Province V, Wang Z, Nemet I, Tang WHW, Hazen SL. Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers-Brief Report. Arterioscler Thromb Vasc Biol. 2024 Sep;44(9):2136-2141. doi: 10.1161/ATVBAHA.124.321019. Epub 2024 Aug 8.
- Background: PubMed 35987213Suez J, Cohen Y, Valdes-Mas R, Mor U, Dori-Bachash M, Federici S, Zmora N, Leshem A, Heinemann M, Linevsky R, Zur M, Ben-Zeev Brik R, Bukimer A, Eliyahu-Miller S, Metz A, Fischbein R, Sharov O, Malitsky S, Itkin M, Stettner N, Harmelin A, Shapiro H, Stein-Thoeringer CK, Segal E, Elinav E. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022 Sep 1;185(18):3307-3328.e19. doi: 10.1016/j.cell.2022.07.016. Epub 2022 Aug 19.
- Individual participant dataSharing planned: Undecided
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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.
Questions about this trial
What is this clinical trial studying?
A study testing Saccharin, Sucralose and Erythritol in people with Prediabetic State and Metabolic Syndrome, run by Charite University, Berlin, Germany.
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 2 inclusion and 6 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: opening soon, as of the sponsor's last update on 29 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
Contact Marco Witkowski, MD, PhD (+49 (0)30 450543775, fs-cpc@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of glucose tolerance (time frame: Baseline vs. within 1 week after intervention). 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 NCT07377097, which also lists 2 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 29 Jan 2026; AzTrials last refreshed its copy on 26 Oct 2026.