Pulse Biomarker Discovery

Study Overview
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Brief Summary
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Dietary pulses, including beans, chickpeas, and lentils, are high in soluble fiber with potential benefits to human health: Pulses are moderate energy density foods, low in fat and high in dietary protein, fiber, vitamins and minerals. Moderate pulse consumption is associated with improvements in glycemic control and reduced risk of cardiovascular disease, obesity and type 2 diabetes. Measuring pulse consumption in humans is difficult, due to limitations in current methods for dietary assessment which are largely based on dietary recalls that are subject to reporting bias. Robust tools for pulse intake assessment are needed, and biomarkers of dietary pulse intake are one approach to solve this problem. The goal of this human feeding study is evaluate the presence of biomarkers of dietary pulses in human subjects.

Detailed Description
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Dietary pulses, including beans, chickpeas, and lentils, are high in soluble fiber with potential benefits to human health: Pulses are moderate energy density foods, low in fat and high in dietary protein, fiber, vitamins and minerals. Moderate pulse consumption is associated with improvements in glycemic control and reduced risk of cardiovascular disease, obesity and type 2 diabetes. However, only 5% of the U.S. population currently meet recommended fiber intakes. As pulses are an excellent source of fiber, increasing their levels in the American diet could lead to demonstrable health benefits in the population, including positive influences on glucose regulation. Additionally, pulse impacts on the gut microbiome may be responsible for reported health benefits. While diet has direct impacts on health, these effects can be mediated by the microbiome, and dietary fiber is a key determinant of this interaction. The fermentation of soluble fiber by specific microbial species lead to the production of short chain fatty acids (SCFAs) including propionate and butyrate which are positively associated with insulin sensitivity. In general, elevated colonic SCFA production is associated with improved glucose regulation, appetite modulation, and immune system modulation. The overall goal of this research is to evaluate how pulse digestion and microbial fermentation influence the circulating and excreted metabolome. To achieve this goal, a randomized controlled feeding study including one week of control, low pulse and high pulse diet will be provided to participants. Metabolomics will be used to identify biomarkers or signatures for pulse enriched diets in urine and plasma. In addition, researchers will investigate dietary pulse related changes in the microbiome community and short chain fatty acid production in fecal samples.

Official Title
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Identifying the Role of Pulses in a Healthful Diet: Metabolomic Signatures of Dietary Pulses and Their Benefits on Cardiometabolic Risk Factors

Conditions
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Body Weight

Intervention / Treatment
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* Other: Control diet
* Other: Low Pulse diet
* Other: High Pulse diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) 18-30 kg/m2 Willingness to provide urine and stool and have blood drawn Exclusion Criteria: Active participation in another research study Tested positive for severe acute respiratory syndrome (SARS) Coronavirus (COV)-2 within the past 10 days Been in close contact with a SARS COV-2 positive person within the past 14 days Unwillingness to consume pulses or pulse-related products Fasting glucose ≥120 mg/dL Fasting triglyceride ≥400 mg/dL LDL-cholesterol ≥160 mg/dL Blood Pressure (BP): Systolic BP ≥140 mmHg or Diastolic BP ≥90 mmHg Current use of dietary supplements and/or unwillingness to cease intake of dietary supplements Vegan or vegetarian lifestyle or any other dietary restrictions that would interfere with consuming the intervention foods and beverages (including dietary intolerances, allergies and sensitivities) Unwillingness to consume intervention foods and beverages Engage in More than moderate drinking (> 1 drink serving per day for women or >2 drink servings per day for men). Binge drinking (4 drinks within two hours). Excessive intake of caffeine containing products (excessive defined as ≥ 400mg/day) Diagnosis of disordered eating or eating disorder Recent diagnosis of any of the following or measurement on screening lab tests Anemia (hemoglobin <11.7g/dL) Abnormal liver function Liver Enzymes that are >200% of upper limit (alanine aminotransferase (ALT) upper limit is 43 U/L or aspartate aminotransferase (AST) upper limit is 54 U/L) History of any of the following Gastric bypass surgery Inflammatory bowel disease (IBD) or other GI conditions that would interfere with consuming the intervention foods Active cancer in the past three years excluding squamous or basal cell carcinomas of the skin that have been handled medically by local excision Other serious medical conditions Recent dental work or have conditions of the oral cavity that would interfere with consuming the intervention foods and beverages Long term use of antibiotics Taking any over the counter or prescribed medication for any of the following Elevated lipids or glucose High blood pressure Weight loss Are pregnant, planning to become pregnant within the duration of the study or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Order of treatments: A: Control diet B: Low pulse diet C: High pulse diet | Other: Control diet<br>* The control Typical American Diet (TAD) diet pattern will mimic the level of intake of fruits, vegetables, whole grains, added sugars, saturated fats and sodium in the general U.S. population. This diet will feature no servings of pulses per day.<br>Other: Low Pulse diet<br>* The Low Pulse diet will be designed based on the TAD with substitution of pulses for lean meat and grains. This diet will feature 0.2 cups of pulses per day at 2,000 kilocalories (kcals).<br>Other: High Pulse diet<br>* The High Pulse diet will be designed based on the TAD with substitution of pulses for lean meat and grains. This diet will feature 1.5 cups of pulses per day at 2,000 kilocalories (kcals).<br>|
| Experimental: Group 2<br>Order of treatments: A: Control diet C: High pulse diet B: Low pulse diet | Other: Control diet<br>* The control Typical American Diet (TAD) diet pattern will mimic the level of intake of fruits, vegetables, whole grains, added sugars, saturated fats and sodium in the general U.S. population. This diet will feature no servings of pulses per day.<br>Other: Low Pulse diet<br>* The Low Pulse diet will be designed based on the TAD with substitution of pulses for lean meat and grains. This diet will feature 0.2 cups of pulses per day at 2,000 kilocalories (kcals).<br>Other: High Pulse diet<br>* The High Pulse diet will be designed based on the TAD with substitution of pulses for lean meat and grains. This diet will feature 1.5 cups of pulses per day at 2,000 kilocalories (kcals).<br>|
| Experimental: Group 3<br>Order of treatments: B: Low pulse diet A: Control diet C: High pulse diet | Other: Control diet<br>* The control Typical American Diet (TAD) diet pattern will mimic the level of intake of fruits, vegetables, whole grains, added sugars, saturated fats and sodium in the general U.S. population. This diet will feature no servings of pulses per day.<br>Other: Low Pulse diet<br>* The Low Pulse diet will be designed based on the TAD with substitution of pulses for lean meat and grains. This diet will feature 0.2 cups of pulses per day at 2,000 kilocalories (kcals).<br>Other: High Pulse diet<br>* The High Pulse diet will be designed based on the TAD with substitution of pulses for lean meat and grains. This diet will feature 1.5 cups of pulses per day at 2,000 kilocalories (kcals).<br>|
| Experimental: Group 4<br>Order of treatments: B: Low pulse diet C: High pulse diet A: Control diet | Other: Control diet<br>* The control Typical American Diet (TAD) diet pattern will mimic the level of intake of fruits, vegetables, whole grains, added sugars, saturated fats and sodium in the general U.S. population. This diet will feature no servings of pulses per day.<br>Other: Low Pulse diet<br>* The Low Pulse diet will be designed based on the TAD with substitution of pulses for lean meat and grains. This diet will feature 0.2 cups of pulses per day at 2,000 kilocalories (kcals).<br>Other: High Pulse diet<br>* The High Pulse diet will be designed based on the TAD with substitution of pulses for lean meat and grains. This diet will feature 1.5 cups of pulses per day at 2,000 kilocalories (kcals).<br>|
| Experimental: Group 5<br>Order of treatments: C: High pulse diet A: Control diet B: Low pulse diet | Other: Control diet<br>* The control Typical American Diet (TAD) diet pattern will mimic the level of intake of fruits, vegetables, whole grains, added sugars, saturated fats and sodium in the general U.S. population. This diet will feature no servings of pulses per day.<br>Other: Low Pulse diet<br>* The Low Pulse diet will be designed based on the TAD with substitution of pulses for lean meat and grains. This diet will feature 0.2 cups of pulses per day at 2,000 kilocalories (kcals).<br>Other: High Pulse diet<br>* The High Pulse diet will be designed based on the TAD with substitution of pulses for lean meat and grains. This diet will feature 1.5 cups of pulses per day at 2,000 kilocalories (kcals).<br>|
| Experimental: Group 6<br>Order of treatments: C: High pulse diet B: Low pulse diet A: Control diet | Other: Control diet<br>* The control Typical American Diet (TAD) diet pattern will mimic the level of intake of fruits, vegetables, whole grains, added sugars, saturated fats and sodium in the general U.S. population. This diet will feature no servings of pulses per day.<br>Other: Low Pulse diet<br>* The Low Pulse diet will be designed based on the TAD with substitution of pulses for lean meat and grains. This diet will feature 0.2 cups of pulses per day at 2,000 kilocalories (kcals).<br>Other: High Pulse diet<br>* The High Pulse diet will be designed based on the TAD with substitution of pulses for lean meat and grains. This diet will feature 1.5 cups of pulses per day at 2,000 kilocalories (kcals).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urine metabolomics profile | Urine metabolites will be measured by gas chromatography mass spectrometry (GCMS) before and after consumption of control, low pulse or high pulse diets. | Day 14, 28, and 42; fasting and post prandial 0.5hr, 2hr, 3hr, 6hr, 12hr and 24hr | 
| Change in plasma metabolomics profile | Plasma metabolites will be measured by gas chromatography mass spectrometry (GCMS) before and after consumption of control, low pulse or high pulse diets. | Day 14, 28, and 42; fasting and post prandial 0.5hr, 2hr, 3hr and 6hr | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fecal microbiome community | DNA of colonic microbiome will be measured before and after each diet exposure. | Day 7, 14, 21, 28, 35, 42 | 
| Change in fecal short chain fatty acids | Acetate, propionate and butyrate will be measured by GCMS before and after each diet exposure. | Day 7, 14, 21, 28, 35, 42 | 
| Change in fecal bile acids | Bile acids will be measured by GCMS before and after each diet exposure. | Day 7, 14, 21, 28, 35, 42 | 
| Change in plasma short-chain fatty acids | Plasma acetate, propionate and butyrate will be measured by GCMS before and after consumption of control, low pulse or high pulse diets. | Day 14, 28, and 42; fasting and post prandial 0.5hr, 2hr, 3hr and 6hr | 
| Change in pro-inflammatory cytokines | Cytokines including tumor necrosis factor alpha (TNF-a), interleukin (IL)-1, IL-6 and interferon-gamma will be measured in plasma using multiplex assays. | Day 14, 28, and 42; fasting and post prandial 0.5hr, 2hr, 3hr and 6hr | 
| Change in anti-inflammatory cytokines | Cytokines including interleukin (IL)-1 receptor antagonist, IL-4, IL-10, IL-11, and IL-13 will be measured in plasma using multiplex assays. | Day 14, 28, and 42; fasting and post prandial 0.5hr, 2hr, 3hr and 6hr | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dietary pulses, Urine biomarkers, Microbiome, Short chain fatty acids, Plasma biomarkers, Fecal biomarkers, Beans, Lentils, Controlled feeding, Intervention, Chickpeas, Metabolomics