## Protocol Section
### Identification Module
**NCT ID:** NCT03427879

**Brief Title:** Effect of Flavonoids on Gut Permeability in Cyclists

**Official Title:** Effect of Flavonoids on Gut Permeability in Cyclists

#### Organization Study ID Info
**ID:** 1010820
#### Organization
**Class:** OTHER
**Full Name:** Utah State University
### Status Module
#### Completion Date
**Date:** 2019-07-31

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2021-02-25

**Type:** ACTUAL

**Last Update Submit Date:** 2021-02-23

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2019-05-15

**Type:** ACTUAL

#### Start Date
**Date:** 2018-09-14

**Type:** ACTUAL

**Status Verified Date:** 2021-02

#### Study First Post Date
**Date:** 2018-02-09
**Type:** ACTUAL
**Study First Submit Date:** 2018-01-30
**Study First Submit QC Date:** 2018-02-02
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Utah State University

#### Responsible Party

**Investigator Affiliation:** Utah State University

**Investigator Full Name:** Robert Ward

**Investigator Title:** Associate Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The purpose of this investigation is to test the hypothesis that chronic supplementation with a dairy-based beverage containing a mixture of blueberry, green tea, and cocoa flavonoids (non-nutritive natural plant compounds) will ameliorate exercise-related changes in gut permeability and inflammation. In a previous feeding study in humans, (NCT02728570) a high flavonoid diet (flavonoids at 340 mg/1000kcal) was effective in mitigating gut permeability and inflammation in overweight and obese adults compared to a low flavonoid diet (10mg/1000 kcal). To test this hypothesis, 20 trained cyclists will complete a randomized crossover study with supplementation for 2 weeks with a dairy-based sports beverage containing either a high flavonoid (approximately 620 mg) or low flavonoid (approximately 5mg) beverage. After the two week intervention, cyclists will complete a 1 hour cycling trial (45 min at 65% VO2 max then 15 minute time trial). The primary endpoints will be gut permeability as measured by plasma intestinal fatty acid binding protein (I-FABP) and the differential sugar test. Secondary endpoints will include gut inflammation (measured via fecal calprotectin), plasma cytokines (IL-6, IL-10 and TNFα) and plasma LPS. In addition, the distance completed in the time trial is a secondary endpoint.

### Conditions Module

**Conditions:**

- Gut Permeability, Gut Inflammation

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** TRIPLE

**Who Masked:**

- PARTICIPANT

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 12

**Type:** ACTUAL

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Subjects will consume 310 milliliters per day of a dairy-based, low flavonoid, sports nutrition recovery beverage 14 days.

**Intervention Names:**

- Drug: Low flavonoid beverage

**Label:** Low flavonoid beverage

**Type:** PLACEBO_COMPARATOR

#### Arm Group 2

**Description:** Subjects will consume 310 milliliters per day of a dairy-based, high flavonoid, sports nutrition recovery beverage 14 days.

**Intervention Names:**

- Drug: High flavonoid beverage

**Label:** High flavonoid beverage

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Low flavonoid beverage

**Description:** A low flavonoid, sports nutrition recovery beverage will be prepared from milk (78%), sugar (8.6%), maltodextrin (8.6%), placebo blueberry powder (2.4%), alkalized cocoa powder (1.6%), and whey protein isolate (0.6%). The beverage will contain approximately 5mg flavonoids per serving.

**Name:** Low flavonoid beverage

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- High flavonoid beverage

**Description:** A high flavonoid, sports nutrition recovery beverage will be prepared from milk (78%), sugar (8.6%), maltodextrin (8.6%), blueberry powder (2.4%), cocoa powder (1.6%), green tea extract (0.1%) and whey protein isolate (0.6%). The beverage will contain approximately 620 mg flavonoids per serving.

**Name:** High flavonoid beverage

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Measure of gut permeability from mouth to end of small intestine. Ratio of urinary lactulose to mannitol after subject consumes a beverage containing these sugars. Sugars in urine are measured by gas chromatography with flame ionization detection.

**Measure:** Urinary lactulose:mannitol ratio by gas chromatography

**Time Frame:** Three weeks

**Description:** Marker of gut wall integrity. i-FABP is measure by enzyme-linked immunosorbent assay in plasma of subjects after the time trial.

**Measure:** Plasma intestinal fatty acid binding protein (i-FABP) by ELISA

**Time Frame:** Three weeks

#### Secondary Outcomes

**Description:** Secondary endpoint for intestinal inflammation. Calprotectin is measured in fecal samples by enzyme-linked immunosorbent assay.

**Measure:** Fecal calprotectin by ELISA

**Time Frame:** Three weeks

**Description:** Secondary measure of gut permeability from mouth to end of colon. Ratio of urinary lactulose to mannitol after subject consumes a beverage containing these sugars. Sugars in urine are measured by gas chromatography with flame ionization detection.

**Measure:** Urinary sucralose:mannitol ratio by gas chromatography

**Time Frame:** Three weeks

**Description:** One of four secondary endpoints for systemic inflammation. The cytokine, TNFa, is measured in plasma by enzyme-linked immunosorbent assay.

**Measure:** Serum soluble tumor necrosis factor (TNFa) by ELISA

**Time Frame:** Three weeks

**Description:** One of four secondary endpoints for systemic inflammation. The cytokine, IL-6, is measured in plasma by enzyme-linked immunosorbent assay.

**Measure:** Serum soluble interleukin-6 (IL-6) by ELISA

**Time Frame:** Three weeks

**Description:** One of four secondary endpoints for systemic inflammation. The cytokine, IL-10, is measured in plasma by enzyme-linked immunosorbent assay.

**Measure:** Serum soluble interleukin-10 by ELISA

**Time Frame:** Three weeks

**Description:** One of four secondary endpoint for systemic inflammation. The bacterial cell wall product is measured in plasma by enzyme-linked immunosorbent assay.

**Measure:** Serum endotoxin by ELISA.

**Time Frame:** Three weeks

**Description:** Subjects will complete a 15m time trial on a bike after each dietary intervention. The distance covered in each time trial will be measured by the computer on the exercise bike.

**Measure:** Distance ridden in time trial

**Time Frame:** One Day

**Description:** Subjects will complete a 15m time trial on a bike after each dietary intervention. This measure is a subjective measure of the difficulty of the work. Subjects will provide the ratings orally during the time trial.

**Measure:** Rating of perceived exertion by questionnaire.

**Time Frame:** One Day

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Male or female of any race or ethnicity between 18 to 49 years of age
* Competed in a road race or triathlon in past 12 months
* Free of chronic disease and GI conditions
* Train at least 3 times per week, 1 hour at a time on average
* Willing to prepare and consume provided pre-workout beverage daily
* Maintain weight (no more/less than 5 kg change)
* Willing to avoid consumption of high flavonoid foods/supplements, large dose vitamin and mineral supplements, and NSAIDs or other medications known to affect inflammation during study period
* Willing to provide urine, stool, and blood samples

Exclusion Criteria:

* Age \<18 or \>50 years
* Medical history of heart disease, hypertension, diabetes, Crohn's disease, IBS, colitis, celiac disease, inflammatory or autoimmune disease, and lactose intolerance
* Uncontrolled hypertension: diastolic blood pressure \>95 mm Hg or systolic blood pressure \>160 mm Hg
* For women: pregnancy, breast feeding or postpartum \<6 months
* Food allergies or restrictions to treatment/placebo beverages
* Chronic use of NSAIDs
* Consumption of flavonoid supplements \<1 month prior to study start
* Antibiotic use \<3 months prior to study start
* Other conditions (medical, psychiatric, or behavioral) that may present a safety hazard to the participant or interfere with study participation, as determined by the principal investigators

**Healthy Volunteers:** True

**Maximum Age:** 49 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Logan

**Country:** United States

**Facility:** Center for Human Nutrition Studies

**State:** Utah

**Zip:** 84322

#### Overall Officials

**Official 1:**

**Affiliation:** Nutrition, Dietetics and Food Sciences, Utah State University

**Name:** Robert E Ward, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M10293

- Name: Inflammation

- Relevance: HIGH

- As Found: Inflammation

### Condition Browse Module - Meshes

- ID: D000007249

- Term: Inflammation

### Intervention Browse Module - Browse Branches

- Abbrev: Ot

- Name: Other Dietary Supplements

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: HB

- Name: Herbal and Botanical

### Intervention Browse Module - Browse Leaves

- ID: T435

- Name: Whey Protein

- Relevance: LOW

- As Found: Unknown

- ID: T312

- Name: Tea

- Relevance: LOW

- As Found: Unknown

- ID: T79

- Name: Blueberry

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
