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Active, not recruitingNCT05318183Updated Nov 20, 2025Results posted

Assessing Gut Microbiota Mediated Health Outcomes of Whole Wheat and Its Major Bioactive Components

An interventional study of Whole Wheat Bread and White Bread (control) in PreDiabetes, Dysbiosis and Endotoxemia, sponsored by Ohio State University. Active, not recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2025-11-20.

Sponsored by Ohio State University · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
65
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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 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.

02

Conditions studied

  • PreDiabetes
  • Dysbiosis
  • Endotoxemia
  • Inflammation

Keywords

  • Gut microbiota
  • Microbiome
  • Metabolomics
  • Prediabetes
  • Glycemic response
  • Intestinal permeability
  • Gut dysbiosis
  • Microbiome metabolism
  • Whole Wheat
  • Phytochemicals
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Fasting blood glucose between 100-125 mg/dL
  • BMI of 30-35 kg/m2

Exclusion criteria

Exclusion Criteria:

  • 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
  • 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
04

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
65 participants (actual)

Study arms

  • Experimental
    Whole Wheat Bread

    Participants consuming 128 g of whole wheat bread (4 slices of bread) daily for two weeks

    Other: Whole Wheat Bread

  • Placebo comparator
    White Bread (control)

    Participants consuming 128 g of white bread (4 slices of bread) daily for two weeks

    Other: White Bread (control)

Interventions

  • OtherWhole Wheat Bread

    Standardized whole wheat bread (128 g daily)

  • OtherWhite Bread (control)

    Standardized white bread (128 g daily)

05

What researchers measure

Primary outcomes

  1. Plasma Glucose

    Data are biomarker area under the time-concentration curve (0-3 hours) on day 14

    Time frame: Day 14 (0, 30, 60, 90, 120, 150, 180 minutes post oral glucose tolerance test)

Secondary outcomes

  1. Plasma Insulin

    Data are biomarker fasting concentrations

    Time frame: Day 14

  2. Plasma Glucose

    Data are biomarker fasting concentrations.

    Time frame: Day 14

  3. Serum C-reactive Protein

    Data are the biomarker serum concentration of C-reactive protein.

    Time frame: Day 14

  4. Serum Tumor Necrosis Factor Alpha

    Data are biomarker serum tumor necrosis factor alpha concentrations.

    Time frame: Day 14

  5. Serum Interleukin-6

    Data are biomarker serum interleukin-6 concentrations.

    Time frame: Day 14

  6. Fecal Calprotectin

    Data are biomarker fecal concentrations.

    Time frame: Day 14

  7. Fecal Myeloperoxidase

    Data are biomarker fecal concentrations.

    Time frame: Day 14

  8. 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.

    Time frame: Day 14

  9. Urine Sucralose/Erythritol

    Data are the sucralose/erythritol ratio measured in urine collected 6-24 h following the digestion of non-digestible sugar probes.

    Time frame: Day 14

  10. Serum Endotoxin

    Data are biomarker fasting concentrations.

    Time frame: Day 14

  11. Serum Myeloperoxidase

    Data are biomarker serum concentrations.

    Time frame: Day 14

  12. Level of Toll-like Receptor 4 Gene Expression

    Data are expression of toll-like receptor 4 gene from peripheral blood mononuclear cells.

    Time frame: Day 14

  13. Myeloid Differentiation Factor 88 Gene Expression

    Expression of myeloid differentiation factor 88 gene from peripheral blood mononuclear cells.

    Time frame: Day 14

  14. Tumor Necrosis Factor Alpha Gene Expression

    Expression of tumor necrosis factor alpha gene from peripheral blood mononuclear cells.

    Time frame: Day 14

  15. p65 Subunit of Nuclear Factor Kappa B Gene Expression

    Expression of p65 subunit of nuclear factor kappa B gene from peripheral blood mononuclear cells.

    Time frame: Day 14

  16. Interleukin-6 Gene Expression

    Expression of interleukin-6 gene from peripheral blood mononuclear cells.

    Time frame: Day 14

  17. Interleukin-8 Gene Expression

    Expression of interleukin-8 gene from peripheral blood mononuclear cells.

    Time frame: Day 14

  18. Myeloperoxidase Gene Expression

    Expression of myeloperoxidase gene from peripheral blood mononuclear cells.

    Time frame: Day 14

  19. Monocyte Chemoattractant Protein-1 Gene Expression

    Expression of monocyte chemoattractant protein-1 gene from peripheral blood mononuclear cells.

    Time frame: Day 14

  20. Fecal Butyrate

    Data are biomarker fecal concentrations.

    Time frame: Day 14

  21. Fecal Acetate

    Data are biomarker fecal concentrations.

    Time frame: Day 14

  22. Fecal Propionate

    Data are biomarker fecal concentrations.

    Time frame: Day 14

  23. Fecal Isobutyric Acid

    Data are biomarker fecal concentrations.

    Time frame: Day 14

  24. Fecal Isovaleric Acid

    Data are biomarker fecal concentrations of isovaleric acid.

    Time frame: Day 14

  25. Serum Alkylersorcinols

    Data are biomarker serum concentrations of alkylresorcinol and alkylresorcinol derivatives.

    Time frame: Day 14

  26. Serum Benoxazinods

    Data are biomarker serum concentrations of benoxazinoids and benoxazinoids derivatives.

    Time frame: Day 14

  27. Serum Phenolic Compounds

    Data are biomarker serum concentrations of phenolic compounds and phenolic derivatives.

    Time frame: Day 14

  28. Fecal Alkylresorcinols

    Data are biomarker fecal concentrations of alkylresorcinols and alkylresorcinol derivatives.

    Time frame: Day 14

  29. Fecal Benoxazinoids

    Data are biomarker fecal concentrations of benoxazinoids and benoxazinoids derivatives.

    Time frame: Day 14

  30. Fecal Phenolic Compounds

    Data are fecal concentrations of phenolic compounds and phenolic derivatives.

    Time frame: Day 14

Other outcomes

  1. Plasma Triglyceride

    Data are biomarker fasting plasma concentrations.

    Time frame: Day 0, Day 14

  2. Plasma Cholesterol Levels

    Data are biomarker fasting plasma concentrations.

    Time frame: Day 14

  3. Plasma HDL-cholesterol

    Data are biomarker fasting plasma concentrations.

    Time frame: Day 14

  4. Serum Alanine Transaminase

    Data are biomarker serum concentrations of alanine transaminase.

    Time frame: Day 14

  5. Serum Interleukin-8

    Data are biomarker serum interleukin-8 concentrations.

    Time frame: Day 14

  6. Gut Microbiota Alpha-diversity Indices

    Alpha-diversity will be determined based on the Shannon-Wiener diversity index. Fecal microbiota assessments and the subsequent determinations of alpha-diversity.

    Time frame: Day 14

  7. Gut Microbiota Beta-diversity Indices

    Beta-diversity will be determined based on the Bray-Curtis diversity index. Fecal microbiota assessments and the subsequent determinations of beta-diversity.

    Time frame: Day 14

  8. Gut Microbiota Relative Abundance

    Gut microbiota relative abundance (percent order, genus, and species level) will be measured in fecal samples.

    Time frame: Day 14

06

Results

Posted Aug 29, 2025

Participant flow

First Intervention (2 Weeks)
Participant flow — First Intervention (2 Weeks)
MilestoneWhole Wheat Bread, Then White BreadWhite Bread (Control), Then Whole Wheat Bread
Started2524
Completed2121
Not completed43
Withdrew: Withdrawal by subject23
Withdrew: Lost to follow-up20
Washout (2 Weeks)
Participant flow — Washout (2 Weeks)
MilestoneWhole Wheat Bread, Then White BreadWhite Bread (Control), Then Whole Wheat Bread
Started2121
Completed2121
Not completed00
Second Intervention (2 Weeks)
Participant flow — Second Intervention (2 Weeks)
MilestoneWhole Wheat Bread, Then White BreadWhite Bread (Control), Then Whole Wheat Bread
Started2121
Completed2118
Not completed03
Withdrew: Protocol violation02
Withdrew: Withdrawal by subject01

Outcome measures

PrimaryPlasma Glucose

Data are biomarker area under the time-concentration curve (0-3 hours) on day 14

Time frame:
Day 14 (0, 30, 60, 90, 120, 150, 180 minutes post oral glucose tolerance test)
Reported as:
Mean · mg/dL x min
Plasma Glucose
mg/dL x minWhole Wheat BreadWhite Bread (Control)
Plasma Glucose4092.15 ± 597.815622.96 ± 644.59
SecondaryPlasma Insulin

Data are biomarker fasting concentrations

Time frame:
Day 14
Reported as:
Mean · uIU/mL
Plasma Insulin
uIU/mLWhole Wheat BreadWhite Bread (Control)
Plasma Insulin18.9 ± 2.816.0 ± 1.6
SecondaryPlasma Glucose

Data are biomarker fasting concentrations.

Time frame:
Day 14
Reported as:
Mean · mg/dL
Plasma Glucose
mg/dLWhole Wheat BreadWhite Bread (Control)
Plasma Glucose93.5 ± 2.685.6 ± 2.3
SecondarySerum C-reactive Protein

Data are the biomarker serum concentration of C-reactive protein.

Time frame:
Day 14
Reported as:
Mean · mg/dL
Serum C-reactive Protein
mg/dLWhole Wheat BreadWhite Bread (Control)
Serum C-reactive Protein0.47 ± 0.10.53 ± 0.1
SecondarySerum Tumor Necrosis Factor Alpha

Data are biomarker serum tumor necrosis factor alpha concentrations.

Time frame:
Day 14
Reported as:
Mean · pg/mL
Serum Tumor Necrosis Factor Alpha
pg/mLWhole Wheat BreadWhite Bread (Control)
Serum Tumor Necrosis Factor Alpha6.39 ± 1.05.63 ± 0.6
SecondarySerum Interleukin-6

Data are biomarker serum interleukin-6 concentrations.

Time frame:
Day 14
Reported as:
Mean · pg/mL
Serum Interleukin-6
pg/mLWhole Wheat BreadWhite Bread (Control)
Serum Interleukin-61.88 ± 0.21.94 ± 0.2
SecondaryFecal Calprotectin

Data are biomarker fecal concentrations.

Time frame:
Day 14
Reported as:
Mean · ug/g
Fecal Calprotectin
ug/gWhole Wheat BreadWhite Bread (Control)
Fecal Calprotectin32.8 ± 4.635.84 ± 5.2
SecondaryFecal Myeloperoxidase

Data are biomarker fecal concentrations.

Time frame:
Day 14
Reported as:
Mean · ng/g
Fecal Myeloperoxidase
ng/gWhole Wheat BreadWhite Bread (Control)
Fecal Myeloperoxidase116 ± 31.5157 ± 20.9
SecondaryUrine 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.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryUrine Sucralose/Erythritol

Data are the sucralose/erythritol ratio measured in urine collected 6-24 h following the digestion of non-digestible sugar probes.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondarySerum Endotoxin

Data are biomarker fasting concentrations.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondarySerum Myeloperoxidase

Data are biomarker serum concentrations.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryLevel of Toll-like Receptor 4 Gene Expression

Data are expression of toll-like receptor 4 gene from peripheral blood mononuclear cells.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryMyeloid Differentiation Factor 88 Gene Expression

Expression of myeloid differentiation factor 88 gene from peripheral blood mononuclear cells.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryTumor Necrosis Factor Alpha Gene Expression

Expression of tumor necrosis factor alpha gene from peripheral blood mononuclear cells.

Time frame:
Day 14

Results for this outcome have not been posted.

Secondaryp65 Subunit of Nuclear Factor Kappa B Gene Expression

Expression of p65 subunit of nuclear factor kappa B gene from peripheral blood mononuclear cells.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryInterleukin-6 Gene Expression

Expression of interleukin-6 gene from peripheral blood mononuclear cells.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryInterleukin-8 Gene Expression

Expression of interleukin-8 gene from peripheral blood mononuclear cells.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryMyeloperoxidase Gene Expression

Expression of myeloperoxidase gene from peripheral blood mononuclear cells.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryMonocyte Chemoattractant Protein-1 Gene Expression

Expression of monocyte chemoattractant protein-1 gene from peripheral blood mononuclear cells.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryFecal Butyrate

Data are biomarker fecal concentrations.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryFecal Acetate

Data are biomarker fecal concentrations.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryFecal Propionate

Data are biomarker fecal concentrations.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryFecal Isobutyric Acid

Data are biomarker fecal concentrations.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryFecal Isovaleric Acid

Data are biomarker fecal concentrations of isovaleric acid.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondarySerum Alkylersorcinols

Data are biomarker serum concentrations of alkylresorcinol and alkylresorcinol derivatives.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondarySerum Benoxazinods

Data are biomarker serum concentrations of benoxazinoids and benoxazinoids derivatives.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondarySerum Phenolic Compounds

Data are biomarker serum concentrations of phenolic compounds and phenolic derivatives.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryFecal Alkylresorcinols

Data are biomarker fecal concentrations of alkylresorcinols and alkylresorcinol derivatives.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryFecal Benoxazinoids

Data are biomarker fecal concentrations of benoxazinoids and benoxazinoids derivatives.

Time frame:
Day 14

Results for this outcome have not been posted.

SecondaryFecal Phenolic Compounds

Data are fecal concentrations of phenolic compounds and phenolic derivatives.

Time frame:
Day 14

Results for this outcome have not been posted.

Other pre-specifiedPlasma Triglyceride

Data are biomarker fasting plasma concentrations.

Time frame:
Day 0, Day 14

Results for this outcome have not been posted.

Other pre-specifiedPlasma Cholesterol Levels

Data are biomarker fasting plasma concentrations.

Time frame:
Day 14

Results for this outcome have not been posted.

Other pre-specifiedPlasma HDL-cholesterol

Data are biomarker fasting plasma concentrations.

Time frame:
Day 14

Results for this outcome have not been posted.

Other pre-specifiedSerum Alanine Transaminase

Data are biomarker serum concentrations of alanine transaminase.

Time frame:
Day 14

Results for this outcome have not been posted.

Other pre-specifiedSerum Interleukin-8

Data are biomarker serum interleukin-8 concentrations.

Time frame:
Day 14

Results for this outcome have not been posted.

Other pre-specifiedGut Microbiota Alpha-diversity Indices

Alpha-diversity will be determined based on the Shannon-Wiener diversity index. Fecal microbiota assessments and the subsequent determinations of alpha-diversity.

Time frame:
Day 14

Results for this outcome have not been posted.

Other pre-specifiedGut Microbiota Beta-diversity Indices

Beta-diversity will be determined based on the Bray-Curtis diversity index. Fecal microbiota assessments and the subsequent determinations of beta-diversity.

Time frame:
Day 14

Results for this outcome have not been posted.

Other pre-specifiedGut Microbiota Relative Abundance

Gut microbiota relative abundance (percent order, genus, and species level) will be measured in fecal samples.

Time frame:
Day 14

Results for this outcome have not been posted.

Adverse events

Collected over 3-months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Whole Wheat Bread0/46 (0%)0/46 (0%)0/46 (0%)
White Bread (Control)0/45 (0%)0/45 (0%)0/45 (0%)

Baseline characteristics

Baseline characteristics of participants with prediabetes at screening.

Age, Categorical
Age, Categorical(Participants)Overall
<=18 years0
Between 18 and 65 years39
>=65 years0
Sex: Female, Male
Sex: Female, Male(Participants)Overall
Female18
Male21
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Overall
Region of Enrollment
Region of Enrollment(participants)Overall
United States39
BMI
BMI(kg/m^2)Overall
Mean34.7 ± 5.2
Fasting plasma glucose
Fasting plasma glucose(mg/dL)Overall
Mean108.7 ± 6.3
Systolic blood pressure
Systolic blood pressure(mmHg)Overall
Mean122.6 ± 10.3
Diastolic blood pressure
Diastolic blood pressure(mmHg)Overall
Mean81.9 ± 7.5

1 further baseline measures are reported on the registry.

07

Study locations

1 site
  • The Ohio State University
    Columbus, Ohio 43210, United States
08

References and documents

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 39378659 ↗

Study documents

  • Protocol and statistical analysis plan · Nov 21, 2021
  • Informed consent form · Apr 19, 2021

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT05318183
Lead sponsor
Ohio State University
Collaborators
United States Department of Agriculture (USDA)
Responsible party
Richard Bruno (Principal Investigator, Ohio State University) — Principal investigator
First posted
Apr 8, 2022
Start date
Jan 27, 2022
Primary completion
May 30, 2024
Completion
May 30, 2026 (estimated)
Results posted
Aug 29, 2025
Last update
Nov 20, 2025

Study contacts

Richard Bruno, PhD, RD
principal investigator · Ohio State University

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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