PreDiabetesNCT05318183
Assessing Gut Microbiota Mediated Health Outcomes of Whole Wheat and Its Major Bioactive Components
A study testing Whole Wheat Bread in people with PreDiabetes and Dysbiosis, run by Ohio State University at 1 site in United States.
Trial summary
This study will investigate the gut microbiota-mediated effects of whole wheat consumption on human health in adults with pre-diabetes. Participants will complete two phases of intervention in random order in which they will consume either whole wheat bread (4 servings) or white bread a day for two weeks prior to… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- PreDiabetes, Dysbiosis, Endotoxemia
- What is being tested?
- Whole Wheat Bread
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jan 2022to 30 May 2026
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Fasting blood glucose between 100-125 mg/dL
- BMI of 30-35 kg/m2
Who cannot join
- History of liver disease, cardiovascular disease, overt diabetes, or cancer
- Prescribed medications for hyperglycemia or dyslipidemia
- Use of dietary supplements, prebiotics, or probiotics
- Usage of antibiotics or anti-fungals within 3 months prior to enrollment
- Smoker
- Alcohol consumption greater than 2 drinks per day
Show all 11Show fewer
- Aerobic exercise greater than 5 hours per week
- Pregnancy or fertility treatments
- History of chronically active inflammatory or neoplastic disease in 3 years prior to enrollment
- History of chronic gastrointestinal disorder including diarrhea, inflammatory bowel disease, celiac disease; coagulation disorders, chronic immunosuppressive medication usage
- History of myocardial infarction or cerebrovascular accident within 6 months prior to participation
Trial locations and contacts
1 site in 1 country.
About this study
This study will investigate the gut microbiota-mediated effects of whole wheat consumption on human health in adults with pre-diabetes. Participants will complete two phases of intervention in random order in which they will consume either whole wheat bread (4 servings) or white bread a day for two weeks prior to collecting specimens (stool, urine, and plasma/serum).
Read the detailed description
Accumulating clinical evidence suggests positive effects of whole grain on cardiometabolic risk. However, outcomes of controlled trials indicate that substantial interpersonal variation occurs in these studies with regard to glucose homeostasis, with some persons being unaffected and others experiencing glucose-lowering effects due to whole wheat bread consumption. Whole grain (whole wheat) contains bioactive phytochemicals in addition to its well-recognized fiber content, and these constituents have not received adequate study to inform dietary recommendations. The objective of this study is to investigate the glucose-lowering effects of whole wheat bread in persons with prediabetes using multi-omics platforms that can provide an understanding of the complex interactions among the gut microbiome, gut metabolome, host metabolome, and gut barrier function. The hypothesis is that gut microbial metabolism of whole wheat and its major bioactive components is a determining factor of human health benefits. This will be tested by conducting a randomized, controlled crossover trial in persons with pre-diabetes who follow a controlled diet containing whole wheat bread or white bread for 2-weeks. Outcomes are expected to significantly advance an understanding of personalized, gut microbiome-mediated approaches in individuals with pre-diabetes to help guide dietary recommendations of whole wheat intake. In addition, novel evidence that maps out the differential functions of diverse genus/species of microbiota to biotransform whole wheat nutrients into more bioactive metabolites are expected.
- Conditions
- PreDiabetes, Dysbiosis, Endotoxemia, Inflammation
- Being tested
- Whole Wheat Bread, White Bread (control)
- Keywords
- Gut microbiota, Microbiome, Metabolomics, Prediabetes, Glycemic response, Intestinal permeability, Gut dysbiosis, Microbiome metabolism, Whole Wheat, Phytochemicals
- Medical subject headings
- Prediabetic State, Dysbiosis, Endotoxemia, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Whole Wheat BreadOther
Standardized whole wheat bread (128 g daily)
White Bread (control)Other
Standardized white bread (128 g daily)
| Study group | Role | What they receive |
|---|---|---|
| Whole Wheat Bread | Experimental | Participants consuming 128 g of whole wheat bread (4 slices of bread) daily for two weeks Receives: Other: Whole Wheat Bread |
| White Bread (control) | Placebo comparator | Participants consuming 128 g of white bread (4 slices of bread) daily for two weeks Receives: Other: White Bread (control) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Glucose
Data are biomarker area under the time-concentration curve (0-3 hours) on day 14
Measured: Day 14 (0, 30, 60, 90, 120, 150, 180 minutes post oral glucose tolerance test)
Secondary outcomes (30)
Plasma Insulin
Data are biomarker fasting concentrations
Measured: Day 14
Plasma Glucose
Data are biomarker fasting concentrations.
Measured: Day 14
Serum C-reactive Protein
Data are the biomarker serum concentration of C-reactive protein.
Measured: Day 14
Serum Tumor Necrosis Factor Alpha
Data are biomarker serum tumor necrosis factor alpha concentrations.
Measured: Day 14
Serum Interleukin-6
Data are biomarker serum interleukin-6 concentrations.
Measured: Day 14
Fecal Calprotectin
Data are biomarker fecal concentrations.
Measured: Day 14
Fecal Myeloperoxidase
Data are biomarker fecal concentrations.
Measured: Day 14
Urine Lactulose/Mannitol
Data are the 24-hour urinary excretion ratio of lactulose relative to mannitol collected 0-5 h following the digestion of non-digestible sugar probes.
Measured: Day 14
Urine Sucralose/Erythritol
Data are the sucralose/erythritol ratio measured in urine collected 6-24 h following the digestion of non-digestible sugar probes.
Measured: Day 14
Serum Endotoxin
Data are biomarker fasting concentrations.
Measured: Day 14
Serum Myeloperoxidase
Data are biomarker serum concentrations.
Measured: Day 14
Level of Toll-like Receptor 4 Gene Expression
Data are expression of toll-like receptor 4 gene from peripheral blood mononuclear cells.
Measured: Day 14
Myeloid Differentiation Factor 88 Gene Expression
Expression of myeloid differentiation factor 88 gene from peripheral blood mononuclear cells.
Measured: Day 14
Tumor Necrosis Factor Alpha Gene Expression
Expression of tumor necrosis factor alpha gene from peripheral blood mononuclear cells.
Measured: Day 14
p65 Subunit of Nuclear Factor Kappa B Gene Expression
Expression of p65 subunit of nuclear factor kappa B gene from peripheral blood mononuclear cells.
Measured: Day 14
Interleukin-6 Gene Expression
Expression of interleukin-6 gene from peripheral blood mononuclear cells.
Measured: Day 14
Interleukin-8 Gene Expression
Expression of interleukin-8 gene from peripheral blood mononuclear cells.
Measured: Day 14
Myeloperoxidase Gene Expression
Expression of myeloperoxidase gene from peripheral blood mononuclear cells.
Measured: Day 14
Monocyte Chemoattractant Protein-1 Gene Expression
Expression of monocyte chemoattractant protein-1 gene from peripheral blood mononuclear cells.
Measured: Day 14
Fecal Butyrate
Data are biomarker fecal concentrations.
Measured: Day 14
Fecal Acetate
Data are biomarker fecal concentrations.
Measured: Day 14
Fecal Propionate
Data are biomarker fecal concentrations.
Measured: Day 14
Fecal Isobutyric Acid
Data are biomarker fecal concentrations.
Measured: Day 14
Fecal Isovaleric Acid
Data are biomarker fecal concentrations of isovaleric acid.
Measured: Day 14
Serum Alkylersorcinols
Data are biomarker serum concentrations of alkylresorcinol and alkylresorcinol derivatives.
Measured: Day 14
Serum Benoxazinods
Data are biomarker serum concentrations of benoxazinoids and benoxazinoids derivatives.
Measured: Day 14
Serum Phenolic Compounds
Data are biomarker serum concentrations of phenolic compounds and phenolic derivatives.
Measured: Day 14
Fecal Alkylresorcinols
Data are biomarker fecal concentrations of alkylresorcinols and alkylresorcinol derivatives.
Measured: Day 14
Fecal Benoxazinoids
Data are biomarker fecal concentrations of benoxazinoids and benoxazinoids derivatives.
Measured: Day 14
Fecal Phenolic Compounds
Data are fecal concentrations of phenolic compounds and phenolic derivatives.
Measured: Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2022
- Study start27 Jan 2022
- Primary completion30 May 2024
- Study completion30 May 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PreDiabetesStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe 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
- Crossover
- Model description
- Participants will be randomized to receive 4 servings per day of whole wheat bread (WWB) or white bread (WB) for 2 weeks. During each study arm, participants will be provided eucaloric standardized diets that are devoid of whole wheat products, probiotic-containing foods, and fermented foods. Before and after each study arm, a fasting blood sample and fecal sample will be obtained for metabolomic and clinical measures. Anthropometric measurements and blood pressure will be assessed at days 0, 7, and 14 of each study arm. On day 14, participants will complete an oral glucose tolerance test (OGTT) with collection of blood samples every 30 minutes for 3 hours and a simultaneous gut permeability test that entails ingesting non-digestible sugar probes and subsequent 24-h collection of urine. Upon completion of these procedures, participants will undergo a \~1 month washout before repeating the study identically, with the crossover to the alternate bread diet.
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Agriculture (USDA)
- Responsible party
- Principal investigator, Richard Bruno, Ohio State University
- Investigators
- Richard Bruno, PhD, RD, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05318183
- Sponsor's protocol ID
- 2021H0347
- Status last verified
- Nov 2025
- First submitted
- 23 Mar 2022
- Last updated
- 20 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Cao S, Pierson JT, Bond AH, Zhang S, Gold A, Zhang H, Zamary KM, Moats P, Teegarden MD, Peterson DG, Mo X, Zhu J, Bruno RS. Intestinal-level anti-inflammatory bioactivities of whole wheat: Rationale, design, and methods of a randomized, controlled, crossover dietary trial in adults with prediabetes. Nutr Res. 2024 Nov;131:83-95. doi: 10.1016/j.nutres.2024.09.010. Epub 2024 Sep 18.
PubMed 39378659Pierson JT, Bond AH, Cao S, Zhang S, Gold A, Zhang H, Zamary KM, Gurer A, Guo C, Bhandari M, Teegarden MD, Peterson DG, Mo X, Zhu J, Bruno RS. Whole wheat bread improves postprandial glucose tolerance in adults with prediabetes: a controlled-feeding randomized crossover trial with microbiome-associated variation in response. Front Nutr. 2026 Aug 28;13:1907908. doi: 10.3389/fnut.2026.1907908. eCollection 2026.
PubMed 42729417
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing Gut Microbiota Mediated Health Outcomes of Whole Wheat and Its Major Bioactive Components
- ClinicalTrials.gov ID
- NCT05318183
- Acronym / sponsor ID
- 2021H0347
- Conditions
- PreDiabetes, Dysbiosis, Endotoxemia, Inflammation
- Keywords
- Gut microbiota, Microbiome, Metabolomics, Prediabetes, Glycemic response, Intestinal permeability, Gut dysbiosis, Microbiome metabolism
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Collaborators
- United States Department of Agriculture (USDA)
- Study start
- 27 Jan 2022 (actual)
- Primary completion
- 30 May 2024 (actual)
- Study completion
- 30 May 2026 (estimated)
- First posted
- 8 Apr 2022 (actual)
- Results
- Posted 29 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate the gut microbiota-mediated effects of whole wheat consumption on human health in adults with pre-diabetes. Participants will complete two phases of intervention in random order in which they will consume either whole wheat bread (4 servings) or white bread a day for two weeks prior to collecting specimens (stool, urine, and plasma/serum).
Detailed description
Accumulating clinical evidence suggests positive effects of whole grain on cardiometabolic risk. However, outcomes of controlled trials indicate that substantial interpersonal variation occurs in these studies with regard to glucose homeostasis, with some persons being unaffected and others experiencing glucose-lowering effects due to whole wheat bread consumption. Whole grain (whole wheat) contains bioactive phytochemicals in addition to its well-recognized fiber content, and these constituents have not received adequate study to inform dietary recommendations. The objective of this study is to investigate the glucose-lowering effects of whole wheat bread in persons with prediabetes using multi-omics platforms that can provide an understanding of the complex interactions among the gut microbiome, gut metabolome, host metabolome, and gut barrier function. The hypothesis is that gut microbial metabolism of whole wheat and its major bioactive components is a determining factor of human health benefits. This will be tested by conducting a randomized, controlled crossover trial in persons with pre-diabetes who follow a controlled diet containing whole wheat bread or white bread for 2-weeks. Outcomes are expected to significantly advance an understanding of personalized, gut microbiome-mediated approaches in individuals with pre-diabetes to help guide dietary recommendations of whole wheat intake. In addition, novel evidence that maps out the differential functions of diverse genus/species of microbiota to biotransform whole wheat nutrients into more bioactive metabolites are expected.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will be randomized to receive 4 servings per day of whole wheat bread (WWB) or white bread (WB) for 2 weeks. During each study arm, participants will be provided eucaloric standardized diets that are devoid of whole wheat products, probiotic-containing foods, and fermented foods. Before and after each study arm, a fasting blood sample and fecal sample will be obtained for metabolomic and clinical measures. Anthropometric measurements and blood pressure will be assessed at days 0, 7, and 14 of each study arm. On day 14, participants will complete an oral glucose tolerance test (OGTT) with collection of blood samples every 30 minutes for 3 hours and a simultaneous gut permeability test that entails ingesting non-digestible sugar probes and subsequent 24-h collection of urine. Upon completion of these procedures, participants will undergo a ~1 month washout before repeating the study identically, with the crossover to the alternate bread diet.
| Arm | Type | Receives |
|---|---|---|
| Whole Wheat Bread | Experimental | Other: Whole Wheat BreadParticipants consuming 128 g of whole wheat bread (4 slices of bread) daily for two weeks |
| White Bread (control) | Placebo comparator | Other: White Bread (control)Participants consuming 128 g of white bread (4 slices of bread) daily for two weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Fasting blood glucose between 100-125 mg/dL
- BMI of 30-35 kg/m2
Key exclusion criteria (11 listed)
- History of liver disease, cardiovascular disease, overt diabetes, or cancer
- Prescribed medications for hyperglycemia or dyslipidemia
- Use of dietary supplements, prebiotics, or probiotics
- Usage of antibiotics or anti-fungals within 3 months prior to enrollment
- Smoker
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 |
|---|---|---|
| Whole Wheat BreadStandardized whole wheat bread (128 g daily) | Other | Whole Wheat Bread |
| White Bread (control)Standardized white bread (128 g daily) | Other | White Bread (control) |
Primary outcome
Plasma Glucose
Time frame: Day 14 (0, 30, 60, 90, 120, 150, 180 minutes post oral glucose tolerance test)
Data are biomarker area under the time-concentration curve (0-3 hours) on day 14
30 secondary outcomes
Plasma Insulin
Time frame: Day 14
Plasma Glucose
Time frame: Day 14
Serum C-reactive Protein
Time frame: Day 14
Serum Tumor Necrosis Factor Alpha
Time frame: Day 14
Serum Interleukin-6
Time frame: Day 14
Fecal Calprotectin
Time frame: Day 14
Fecal Myeloperoxidase
Time frame: Day 14
Urine Lactulose/Mannitol
Time frame: Day 14
Urine Sucralose/Erythritol
Time frame: Day 14
Serum Endotoxin
Time frame: Day 14
Serum Myeloperoxidase
Time frame: Day 14
Level of Toll-like Receptor 4 Gene Expression
Time frame: Day 14
Myeloid Differentiation Factor 88 Gene Expression
Time frame: Day 14
Tumor Necrosis Factor Alpha Gene Expression
Time frame: Day 14
p65 Subunit of Nuclear Factor Kappa B Gene Expression
Time frame: Day 14
Interleukin-6 Gene Expression
Time frame: Day 14
Interleukin-8 Gene Expression
Time frame: Day 14
Myeloperoxidase Gene Expression
Time frame: Day 14
Monocyte Chemoattractant Protein-1 Gene Expression
Time frame: Day 14
Fecal Butyrate
Time frame: Day 14
Fecal Acetate
Time frame: Day 14
Fecal Propionate
Time frame: Day 14
Fecal Isobutyric Acid
Time frame: Day 14
Fecal Isovaleric Acid
Time frame: Day 14
Serum Alkylersorcinols
Time frame: Day 14
Serum Benoxazinods
Time frame: Day 14
Serum Phenolic Compounds
Time frame: Day 14
Fecal Alkylresorcinols
Time frame: Day 14
Fecal Benoxazinoids
Time frame: Day 14
Fecal Phenolic Compounds
Time frame: Day 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 39378659Cao S, Pierson JT, Bond AH, Zhang S, Gold A, Zhang H, Zamary KM, Moats P, Teegarden MD, Peterson DG, Mo X, Zhu J, Bruno RS. Intestinal-level anti-inflammatory bioactivities of whole wheat: Rationale, design, and methods of a randomized, controlled, crossover dietary trial in adults with prediabetes. Nutr Res. 2024 Nov;131:83-95. doi: 10.1016/j.nutres.2024.09.010. Epub 2024 Sep 18.
- Derived from this study: PubMed 42729417Pierson JT, Bond AH, Cao S, Zhang S, Gold A, Zhang H, Zamary KM, Gurer A, Guo C, Bhandari M, Teegarden MD, Peterson DG, Mo X, Zhu J, Bruno RS. Whole wheat bread improves postprandial glucose tolerance in adults with prediabetes: a controlled-feeding randomized crossover trial with microbiome-associated variation in response. Front Nutr. 2026 Aug 28;13:1907908. doi: 10.3389/fnut.2026.1907908. eCollection 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.
Richard Bruno, PhD, RD principal investigator
Ohio State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Whole Wheat Bread in people with PreDiabetes and Dysbiosis, run by Ohio State University 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 2 inclusion and 11 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 20 Nov 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. 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?
Yes. Results are posted in the registry (first posted 29 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Plasma Glucose (time frame: Day 14 (0, 30, 60, 90, 120, 150, 180 minutes post oral glucose tolerance test)). 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 NCT05318183, 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 20 Nov 2025.