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| Name | Class |
|---|---|
| United States Department of Agriculture (USDA) | FED |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Whole Wheat Bread | Experimental | Participants consuming 128 g of whole wheat bread (4 slices of bread) daily for two weeks |
|
| White Bread (control) | Placebo Comparator | Participants consuming 128 g of white bread (4 slices of bread) daily for two weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Whole Wheat Bread | Other | Standardized whole wheat bread (128 g daily) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Glucose | Data are biomarker area under the time-concentration curve (0-3 hours) on day 14 | Day 14 (0, 30, 60, 90, 120, 150, 180 minutes post oral glucose tolerance test) |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Insulin | Data are biomarker fasting concentrations | Day 14 |
| Plasma Glucose | Data are biomarker fasting concentrations. | Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Triglyceride | Data are biomarker fasting plasma concentrations. | Day 0, Day 14 |
| Plasma Cholesterol Levels | Data are biomarker fasting plasma concentrations. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Richard Bruno, PhD, RD | Ohio State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Ohio State University | Columbus | Ohio | 43210 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39378659 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Whole Wheat Bread, Then White Bread | Participants consuming 128 g of whole wheat bread (4 slices of bread) daily for two weeks, followed by a 2-week washout period, then consumed white bread daily for 2 weeks. Whole Wheat Bread: Standardized whole wheat bread (128 g daily) |
| FG001 | White Bread (Control), Then Whole Wheat Bread | Participants consumed 128 g of white bread (4 slices of bread) daily for two weeks, followed by a 2-week washout period, and then consumed whole wheat bread daily for an additional 2 weeks. White Bread (control): Standardized white bread (128 g daily) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (2 Weeks) |
|
| |||||||||||||||||||||
| Washout (2 Weeks) |
| ||||||||||||||||||||||
| Second Intervention (2 Weeks) |
|
Baseline characteristics of participants with prediabetes at screening.
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall | Baseline characteristics of participants at screening |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Plasma Glucose | Data are biomarker area under the time-concentration curve (0-3 hours) on day 14 | Posted | Mean | Standard Error | mg/dL x min | Day 14 (0, 30, 60, 90, 120, 150, 180 minutes post oral glucose tolerance test) |
|
3-months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Whole Wheat Bread | Participants consuming 128 g of whole wheat bread (4 slices of bread) daily for two weeks Whole Wheat Bread: Standardized whole wheat bread (128 g daily) |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Richard Bruno | The Ohio State University | 614.292.5522 | bruno.27@osu.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 21, 2021 | Jun 1, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 19, 2021 | May 29, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D011236 | Prediabetic State |
| D064806 | Dysbiosis |
| D019446 | Endotoxemia |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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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.
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| White Bread (control) |
| Other |
Standardized white bread (128 g daily) |
|
| Serum C-reactive Protein | Data are the biomarker serum concentration of C-reactive protein. | Day 14 |
| Serum Tumor Necrosis Factor Alpha | Data are biomarker serum tumor necrosis factor alpha concentrations. | Day 14 |
| Serum Interleukin-6 | Data are biomarker serum interleukin-6 concentrations. | Day 14 |
| Fecal Calprotectin | Data are biomarker fecal concentrations. | Day 14 |
| Fecal Myeloperoxidase | Data are biomarker fecal concentrations. | 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. | 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. | Day 14 |
| Serum Endotoxin | Data are biomarker fasting concentrations. | Day 14 |
| Serum Myeloperoxidase | Data are biomarker serum concentrations. | Day 14 |
| Level of Toll-like Receptor 4 Gene Expression | Data are expression of toll-like receptor 4 gene from peripheral blood mononuclear cells. | Day 14 |
| Myeloid Differentiation Factor 88 Gene Expression | Expression of myeloid differentiation factor 88 gene from peripheral blood mononuclear cells. | Day 14 |
| Tumor Necrosis Factor Alpha Gene Expression | Expression of tumor necrosis factor alpha gene from peripheral blood mononuclear cells. | 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. | Day 14 |
| Interleukin-6 Gene Expression | Expression of interleukin-6 gene from peripheral blood mononuclear cells. | Day 14 |
| Interleukin-8 Gene Expression | Expression of interleukin-8 gene from peripheral blood mononuclear cells. | Day 14 |
| Myeloperoxidase Gene Expression | Expression of myeloperoxidase gene from peripheral blood mononuclear cells. | Day 14 |
| Monocyte Chemoattractant Protein-1 Gene Expression | Expression of monocyte chemoattractant protein-1 gene from peripheral blood mononuclear cells. | Day 14 |
| Fecal Butyrate | Data are biomarker fecal concentrations. | Day 14 |
| Fecal Acetate | Data are biomarker fecal concentrations. | Day 14 |
| Fecal Propionate | Data are biomarker fecal concentrations. | Day 14 |
| Fecal Isobutyric Acid | Data are biomarker fecal concentrations. | Day 14 |
| Fecal Isovaleric Acid | Data are biomarker fecal concentrations of isovaleric acid. | Day 14 |
| Serum Alkylersorcinols | Data are biomarker serum concentrations of alkylresorcinol and alkylresorcinol derivatives. | Day 14 |
| Serum Benoxazinods | Data are biomarker serum concentrations of benoxazinoids and benoxazinoids derivatives. | Day 14 |
| Serum Phenolic Compounds | Data are biomarker serum concentrations of phenolic compounds and phenolic derivatives. | Day 14 |
| Fecal Alkylresorcinols | Data are biomarker fecal concentrations of alkylresorcinols and alkylresorcinol derivatives. | Day 14 |
| Fecal Benoxazinoids | Data are biomarker fecal concentrations of benoxazinoids and benoxazinoids derivatives. | Day 14 |
| Fecal Phenolic Compounds | Data are fecal concentrations of phenolic compounds and phenolic derivatives. | Day 14 |
| Day 14 |
| Plasma HDL-cholesterol | Data are biomarker fasting plasma concentrations. | Day 14 |
| Serum Alanine Transaminase | Data are biomarker serum concentrations of alanine transaminase. | Day 14 |
| Serum Interleukin-8 | Data are biomarker serum interleukin-8 concentrations. | Day 14 |
| 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. | Day 14 |
| 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. | Day 14 |
| Gut Microbiota Relative Abundance | Gut microbiota relative abundance (percent order, genus, and species level) will be measured in fecal samples. | Day 14 |
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| NOT COMPLETED |
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| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| BMI | Mean | Standard Deviation | kg/m^2 |
|
| Fasting plasma glucose | Mean | Standard Deviation | mg/dL |
|
| Systolic blood pressure | Mean | Standard Deviation | mmHg |
|
| Diastolic blood pressure | Mean | Standard Deviation | mmHg |
|
| Waist circumference | Mean | Standard Deviation | cm |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Plasma Insulin | Data are biomarker fasting concentrations | Posted | Mean | Standard Error | uIU/mL | Day 14 |
|
|
|
| Secondary | Plasma Glucose | Data are biomarker fasting concentrations. | Posted | Mean | Standard Error | mg/dL | Day 14 |
|
|
|
| Secondary | Serum C-reactive Protein | Data are the biomarker serum concentration of C-reactive protein. | Posted | Mean | Standard Error | mg/dL | Day 14 |
|
|
|
| Secondary | Serum Tumor Necrosis Factor Alpha | Data are biomarker serum tumor necrosis factor alpha concentrations. | Posted | Mean | Standard Error | pg/mL | Day 14 |
|
|
|
| Secondary | Serum Interleukin-6 | Data are biomarker serum interleukin-6 concentrations. | Posted | Mean | Standard Error | pg/mL | Day 14 |
|
|
|
| Secondary | Fecal Calprotectin | Data are biomarker fecal concentrations. | Posted | Mean | Standard Error | ug/g | Day 14 |
|
|
|
| Secondary | Fecal Myeloperoxidase | Data are biomarker fecal concentrations. | Posted | Mean | Standard Error | ng/g | Day 14 |
|
|
|
| Secondary | 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. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Urine Sucralose/Erythritol | Data are the sucralose/erythritol ratio measured in urine collected 6-24 h following the digestion of non-digestible sugar probes. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Serum Endotoxin | Data are biomarker fasting concentrations. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Serum Myeloperoxidase | Data are biomarker serum concentrations. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Level of Toll-like Receptor 4 Gene Expression | Data are expression of toll-like receptor 4 gene from peripheral blood mononuclear cells. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Myeloid Differentiation Factor 88 Gene Expression | Expression of myeloid differentiation factor 88 gene from peripheral blood mononuclear cells. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Tumor Necrosis Factor Alpha Gene Expression | Expression of tumor necrosis factor alpha gene from peripheral blood mononuclear cells. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | p65 Subunit of Nuclear Factor Kappa B Gene Expression | Expression of p65 subunit of nuclear factor kappa B gene from peripheral blood mononuclear cells. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Interleukin-6 Gene Expression | Expression of interleukin-6 gene from peripheral blood mononuclear cells. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Interleukin-8 Gene Expression | Expression of interleukin-8 gene from peripheral blood mononuclear cells. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Myeloperoxidase Gene Expression | Expression of myeloperoxidase gene from peripheral blood mononuclear cells. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Monocyte Chemoattractant Protein-1 Gene Expression | Expression of monocyte chemoattractant protein-1 gene from peripheral blood mononuclear cells. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Fecal Butyrate | Data are biomarker fecal concentrations. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Fecal Acetate | Data are biomarker fecal concentrations. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Fecal Propionate | Data are biomarker fecal concentrations. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Fecal Isobutyric Acid | Data are biomarker fecal concentrations. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Fecal Isovaleric Acid | Data are biomarker fecal concentrations of isovaleric acid. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Serum Alkylersorcinols | Data are biomarker serum concentrations of alkylresorcinol and alkylresorcinol derivatives. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Serum Benoxazinods | Data are biomarker serum concentrations of benoxazinoids and benoxazinoids derivatives. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Serum Phenolic Compounds | Data are biomarker serum concentrations of phenolic compounds and phenolic derivatives. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Fecal Alkylresorcinols | Data are biomarker fecal concentrations of alkylresorcinols and alkylresorcinol derivatives. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Fecal Benoxazinoids | Data are biomarker fecal concentrations of benoxazinoids and benoxazinoids derivatives. | Not Posted | May 2026 | Day 14 | Participants |
| Secondary | Fecal Phenolic Compounds | Data are fecal concentrations of phenolic compounds and phenolic derivatives. | Not Posted | May 2026 | Day 14 | Participants |
| Other Pre-specified | Plasma Triglyceride | Data are biomarker fasting plasma concentrations. | Not Posted | May 2026 | Day 0, Day 14 | Participants |
| Other Pre-specified | Plasma Cholesterol Levels | Data are biomarker fasting plasma concentrations. | Not Posted | May 2026 | Day 14 | Participants |
| Other Pre-specified | Plasma HDL-cholesterol | Data are biomarker fasting plasma concentrations. | Not Posted | May 2026 | Day 14 | Participants |
| Other Pre-specified | Serum Alanine Transaminase | Data are biomarker serum concentrations of alanine transaminase. | Not Posted | May 2026 | Day 14 | Participants |
| Other Pre-specified | Serum Interleukin-8 | Data are biomarker serum interleukin-8 concentrations. | Not Posted | May 2026 | Day 14 | Participants |
| Other Pre-specified | 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. | Not Posted | May 2026 | Day 14 | Participants |
| Other Pre-specified | 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. | Not Posted | May 2026 | Day 14 | Participants |
| Other Pre-specified | Gut Microbiota Relative Abundance | Gut microbiota relative abundance (percent order, genus, and species level) will be measured in fecal samples. | Not Posted | May 2026 | Day 14 | Participants |
| 0 |
| 46 |
| 0 |
| 46 |
| 0 |
| 46 |
| EG001 | White Bread (Control) | Participants consuming 128 g of white bread (4 slices of bread) daily for two weeks White Bread (control): Standardized white bread (128 g daily) | 0 | 45 | 0 | 45 | 0 | 45 |
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| D004700 | Endocrine System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D016470 | Bacteremia |
| D018805 | Sepsis |
| D007239 | Infections |
| D014115 | Toxemia |
| D018746 | Systemic Inflammatory Response Syndrome |