MASLDNCT06329544
High Fructose Diet, the Gut Microbiome, and Metabolic Health
A study testing Fructose and glucose in people with MASLD and Type 2 Diabetes, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
Americans commonly consume excess amounts of dietary fructose. Added fructose has been shown to have an adverse impact on metabolic health, including increased insulin resistance and type 2 diabetes (T2D) risk. However, the mechanisms that link dietary fructose and metabolic health are poorly understood. Read more about this study
- Who is it for?
- Ages 25 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- MASLD, Type 2 Diabetes, Obesity
- What is being tested?
- Fructose and glucose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Oct 2024to 31 Aug 2028
- 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 25 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants must be determined to be a fructose malabsorber (screening visit) via hydrogen breath test.
Who cannot join
- Use of probiotic/prebiotic/synbiotic supplements
- Consumption of > 1 sugar sweetened beverage per day
- Antibiotics within 3 months prior to enrollment or during intervention
- Vegetarian, vegan or other restrictive dietary habits
- Food allergy
- Alcohol consumption in excess of 2 drink per day
Show all 15Show fewer
- The following additional factors will be exclusion criteria:
- Physician diagnosis of a major medical illness (including type 1 or type 2 diabetes) or eating disorder
- Physical, mental, or cognitive handicaps that prevent participation
- Chronic use of any medication that may affect body weight or composition, insulin resistance, or lipid profiles;
- Current smoking (more than 1 cigarette in the past week) or use of other recreational drugs; e) restrictive dietary habits;
- food allergy;
- excess alcohol consumption;
- recent use of pro-, pre- or Synbiotics of receipt of antibiotics within 3 months prior to enrollment or during the intervention;
- consumption of greater than 1 sugar sweetened beverage per day prior to enrollment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Mount Sinai Morningside
New York, New York, 10025
Ryan Walker
About this study
Official title: The Effects of a High Fructose Diet on the Gut Microbiome and Metabolic Health: A Controlled Clinical Intervention Study
Americans commonly consume excess amounts of dietary fructose. Added fructose has been shown to have an adverse impact on metabolic health, including increased insulin resistance and type 2 diabetes (T2D) risk. However, the mechanisms that link dietary fructose and metabolic health are poorly understood. Malabsorption or incomplete metabolism of fructose in the small intestine is common in the population. Excess fructose reaches the colon where it may change the structure and function of the gut microbiome, alter bacterial metabolites and trigger inflammatory responses impacting T2D risk. To elucidate whether commonly consumed levels of dietary fructose influence metabolic outcomes through altering the gut microbiome, the research team will randomize 30 participants to a controlled cross-over dietary intervention, in which the participants will consume 12-day isocaloric, added fructose or glucose diets (25% of total calories) separated by a 10-day controlled diet washout period.
The research team aims to:
Read more
- Determine the relationships between high fructose consumption, the gut microbiome and metabolic risk.
- Characterize the causal role(s) that fructose-induced alterations to the gut microbiome have on metabolic risk using a germ-free mouse model.
The research team will measure 1) microbiota community structure and function via metagenomic sequencing of stool, 2) fecal metabolites via targeted and untargeted metabolomics, 3) anthropometrics, 4) insulin resistance, serum markers of T2D risk and inflammatory cytokines, 5) fecal microbial carbohydrate oxidation capacity and 6) liver fat via MRI elastography. The research team will use novel statistical approaches, including Distributed Lag Modeling, to understand the complex relationships between diet, the microbiome, metabolites and health outcomes.
The research team will then conduct controlled dietary interventions and fecal microbiome transplantation studies in germ-free mice. Donor fecal samples from human participants in both the glucose and fructose arms of the clinical intervention will be transplanted into germ-free and colonized mice to establish a causal relationship between fructose-induced changes to the gut microbiome, liver fat and metabolic and inflammatory changes known to increase risk for T2D.
The research team aims to comprehensively assess the structural and functional changes to the gut microbiome brought about by a high fructose diet. Determining the impact of excess fructose on the microbiome will help identify novel means by which fructose contributes to metabolic disease risk. In addition to identifying strategies to improve metabolic health in adults, data from this proposal could help inform targeted approaches to mitigate future disease risk in vulnerable populations that consume high levels of fructose, such as children.
- Conditions
- MASLD, Type 2 Diabetes, Obesity
- Being tested
- Fructose, glucose
- Keywords
- Microbiome, MASLD, Obesity, Fructose, Fatty Liver
- Medical subject headings
- Diabetes Mellitus, Type 2, Obesity, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FructoseDietary supplement
12-day isocaloric weight-maintaining high fructose diet (25% total calories from added fructose)
glucoseDietary supplement
12-day isocaloric weight-maintaining high glucose diet (25% total calories from added glucose)
| Study group | Role | What they receive |
|---|---|---|
| Fructose Dietary then Glucose Dietary | Experimental | Participants that will be randomized to the 12-day isocaloric weight-maintaining high fructose diet, then will change to the 12-day isocaloric weight-maintaining high glucose diet after a 10-day washout period. Receives: Dietary Supplement: Fructose; Dietary Supplement: glucose |
| Glucose Dietary then Fructose Dietary | Experimental | Participants that will be randomized to the 12-day isocaloric weight-maintaining high glucose diet, then will change to the12-day isocaloric weight-maintaining high fructose diet after a 10-day washout period. Receives: Dietary Supplement: Fructose; Dietary Supplement: glucose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver proton density fat fraction (PDFF)
Liver proton density fat fraction (PDFF) in %
Measured: year 3
Degree of fibrosis
Tissue shear stiffness will be measured in the right hepatic lobe [in kilopascals (kPa)] to assess the degree of fibrosis.
Measured: year 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2024
- Study start8 Oct 2024
- Primary completion31 Aug 2028 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MASLDStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The study will be a double-blinded (participants and select study personnel), randomized controlled crossover dietary intervention design.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- Metabolic Solutions Inc., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Principal investigator, Ryan Walker, Icahn School of Medicine at Mount Sinai
- Investigators
- Ryan Walker, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06329544
- Sponsor's protocol ID
- STUDY-23-01572
- Other IDs
- 1R01DK137968-01
- Status last verified
- Nov 2025
- First submitted
- 18 Mar 2024
- Last updated
- 17 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial, after deidentification.
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of a High Fructose Diet on the Gut Microbiome and Metabolic Health: A Controlled Clinical Intervention Study
- ClinicalTrials.gov ID
- NCT06329544
- Acronym / sponsor ID
- STUDY-23-01572
- Conditions
- MASLD, Type 2 Diabetes, Obesity
- Keywords
- Microbiome, MASLD, Obesity, Fructose, Fatty Liver
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- Metabolic Solutions Inc., National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 8 Oct 2024 (actual)
- Primary completion
- 31 Aug 2028 (estimated)
- Study completion
- 31 Aug 2028 (estimated)
- First posted
- 26 Mar 2024 (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.
Americans commonly consume excess amounts of dietary fructose. Added fructose has been shown to have an adverse impact on metabolic health, including increased insulin resistance and type 2 diabetes (T2D) risk. However, the mechanisms that link dietary fructose and metabolic health are poorly understood. Malabsorption or incomplete metabolism of fructose in the small intestine is common in the population. Excess fructose reaches the colon where it may change the structure and function of the gut microbiome, alter bacterial metabolites and trigger inflammatory responses impacting T2D risk. To elucidate whether commonly consumed levels of dietary fructose influence metabolic outcomes through altering the gut microbiome, the research team will randomize 30 participants to a controlled cross-over dietary intervention, in which the participants will consume 12-day isocaloric, added fructose or glucose diets (25% of total calories) separated by a 10-day controlled diet washout period.
The research team aims to:
- Determine the relationships between high fructose consumption, the gut microbiome and metabolic risk.
- Characterize the causal role(s) that fructose-induced alterations to the gut microbiome have on metabolic risk using a germ-free mouse model.
The research team will measure 1) microbiota community structure and function via metagenomic sequencing of stool, 2) fecal metabolites via targeted and untargeted metabolomics, 3) anthropometrics, 4) insulin resistance, serum markers of T2D risk and inflammatory cytokines, 5) fecal microbial carbohydrate oxidation capacity and 6) liver fat via MRI elastography. The research team will use novel statistical approaches, including Distributed Lag Modeling, to understand the complex relationships between diet, the microbiome, metabolites and health outcomes.
The research team will then conduct controlled dietary interventions and fecal microbiome transplantation studies in germ-free mice. Donor fecal samples from human participants in both the glucose and fructose arms of the clinical intervention will be transplanted into germ-free and colonized mice to establish a causal relationship between fructose-induced changes to the gut microbiome, liver fat and metabolic and inflammatory changes known to increase risk for T2D.
The research team aims to comprehensively assess the structural and functional changes to the gut microbiome brought about by a high fructose diet. Determining the impact of excess fructose on the microbiome will help identify novel means by which fructose contributes to metabolic disease risk. In addition to identifying strategies to improve metabolic health in adults, data from this proposal could help inform targeted approaches to mitigate future disease risk in vulnerable populations that consume high levels of fructose, such as children.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- The study will be a double-blinded (participants and select study personnel), randomized controlled crossover dietary intervention design.
| Arm | Type | Receives |
|---|---|---|
| Fructose Dietary then Glucose Dietary | Experimental | Dietary Supplement: Fructose, Dietary Supplement: glucoseParticipants that will be randomized to the 12-day isocaloric weight-maintaining high fructose diet, then will change to the 12-day isocaloric weight-maintaining high glucose diet after a 10-day washout period. |
| Glucose Dietary then Fructose Dietary | Experimental | Dietary Supplement: Fructose, Dietary Supplement: glucoseParticipants that will be randomized to the 12-day isocaloric weight-maintaining high glucose diet, then will change to the12-day isocaloric weight-maintaining high fructose diet after a 10-day washout period. |
Who may qualify
- Ages
- 25 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Participants must be determined to be a fructose malabsorber (screening visit) via hydrogen breath test.
Key exclusion criteria (15 listed)
- Use of probiotic/prebiotic/synbiotic supplements
- Consumption of > 1 sugar sweetened beverage per day
- Antibiotics within 3 months prior to enrollment or during intervention
- Vegetarian, vegan or other restrictive dietary habits
- Food allergy
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 |
|---|---|---|
| Fructose12-day isocaloric weight-maintaining high fructose diet (25% total calories from added fructose) | Dietary supplement | Fructose Dietary then Glucose Dietary, Glucose Dietary then Fructose Dietary |
| glucose12-day isocaloric weight-maintaining high glucose diet (25% total calories from added glucose) | Dietary supplement | Fructose Dietary then Glucose Dietary, Glucose Dietary then Fructose Dietary |
Primary outcome
Liver proton density fat fraction (PDFF)
Time frame: year 3
Liver proton density fat fraction (PDFF) in %
Degree of fibrosis
Time frame: year 3
Tissue shear stiffness will be measured in the right hepatic lobe [in kilopascals (kPa)] to assess the degree of fibrosis.
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 17 Dec 2025.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial, after deidentification.
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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.
Ryan Walker principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fructose and glucose in people with MASLD and Type 2 Diabetes, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
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 1 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 17 Dec 2025. 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 United States. 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?
Contact Ryan Walker, PhD (212-824-7088, ryan.walker@mssm.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liver proton density fat fraction (PDFF) (time frame: year 3). 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?
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 17 Dec 2025.