Beetroot Juice NO Cold Study (NCS)

Beetroot Juice Supplement for Boosting Mucosal Immunity - The NO Cold Study

Currently, there is a lack of evidence-based prevention strategies for respiratory infection and management of these conditions can be costly to the public. Airway nitric oxide provides a first line of defense against pathogens, and beetroot juice, a source of dietary nitrate, has been shown to elevate nitric oxide. The main objective of this project is to demonstrate that one week of supplementation with beetroot juice elevates airway nitric oxide during stressful periods in young adults and thereby can protect against respiratory viral infections.

Study Overview

• Status: Recruiting
• Conditions: Respiratory Tract Infections; Cold Symptoms; Exhaled Nitric Oxide
• Intervention / Treatment: Dietary supplement: Beetroot juice

Detailed Description

Study Title Beetroot Juice Supplement for Boosting Mucosal Immunity: The NO Cold Study

Objectives Aim 1: Demonstrate that a 7-day trial of daily beetroot juice or nitrate depleted placebo beetroot juice is feasible with acceptable retention and adherence during a period of real-life stress, using adherence monitoring of beetroot juice intake by cell phone recorded video; acceptable burdensomeness for participants and success of team coordination and study logistics should also be demonstrated.

Aim 2: Generate initial estimates of effect size for a) elevations in exhaled nitric oxide (FENO) and b) the correlation between changes in FENO and both infection reduction and cold symptom reduction (biological signature).

Aim 3: a) Examine if 2 daily doses of beetroot juice are more potent than 1 daily dose in elevating FENO, and b) investigate whether each beetroot juice dosage (1 dose and 2 doses) increases FENO more than the placebo.

Exploratory aims: Explore sex as a moderator of all the Aims. Also explore effects of competitors/inhibitors of NO (arginase, asymmetric dimethylarginine) in a) reducing FENO under stress, and b) whether beetroot juice buffers any of these potential adverse effects on FENO; c) investigate whether effects of stress cortisol, which negatively impact NO, cold symptoms, and respiratory infections, are also buffered by beetroot juice.

Design and Outcomes This is a double-blind, placebo controlled clinical trial to test the efficacy of beetroot juice as elevating airway NO, which is associated with reduced cold symptoms and respiratory viral infection rates, in undergraduate students aged 18-30.

Interventions and Duration Participants will be receiving 1 active daily dose of beetroot juice and 1 dose of nitrate-depleted placebo beetroot juice, 2 active daily doses of beetroot juice, or 2 daily doses of nitrate-depleted placebo beetroot.

Cold symptoms will be explored by questionnaire at baseline (in a low stress period during the semester) and subsequently twice during the final exam period, once at an early stage of the finals (days 1-3 of the final exam period), and once at a later stage (days 4-6). A follow-up online questionnaire packet will be administered 3 days after the last final day. FENO, sampling for viral PCR, salivary cortisol, and exhaled breath condensate will be undertaken at baseline, early finals, and late finals (in-person assessments are not feasible at follow-up, because students leave campus after finals).

Sample Size and Population The sample size is 150 students (n=66 at SMU site, n=84 at Baylor site). Female and male students 18-30 years old will be recruited from Baylor and SMU. The investigators will make an extra effort to guarantee equal representation of both genders. Participants can be from any ethnic or cultural background, as long as they can understand and read English adequately. The student population of both universities combined is diverse (28.5-38.5% minorities).

The investigators will stratify by sex and by site, to randomize participants to receiving 1 active daily dose of beetroot juice and 1 dose of nitrate-depleted placebo beetroot juice, 2 active daily doses of beetroot juice, or 2 daily doses of nitrate-depleted placebo beetroot juice (n=50 per group).

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Savannah Springfield, BA; Phone Number: (214) 768-6441; Email: sspringfield@mail.smu.edu
• Study Contact Backup: Name: Danielle Young, Ph.D.; Phone Number: (254) 710-2236; Email: Danielle_Young@baylor.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75206
      • Recruiting
      • Southern Methodist University
      • Contact: Savannah Springfield, BA; Phone Number: 214-768-6441; Email: sspringfield@smu.edu
    • Waco, Texas, United States, 76796
      • Recruiting
      • Baylor University
      • Contact: Danielle Young, Ph.D.; Phone Number: 254-710-2236; Email: Danielle_Young@baylor.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Individuals will be included:

• SMU or Baylor University students
• Ages of 18-30 years old.

Exclusion Criteria:

• Active smokers
• Smoking cannabis or vape
• Students with clinically significant asthma
• COPD and emphysema
• Allergic rhinitis
• High levels of exhaled nitric oxide (FENO ≥40ppb)
• Developing kidney stone
• Clinically significant heart disease
• Cerebrovascular disease
• Thyroid dysfunction
• Out-of-control diabetes
• Significant current problems with schizophrenia, psychosis, mood disorders, suicidality, and drug or alcohol dependence or abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Two active doses of beetroot juice; 2 active (nitrate containing) doses of Beet-it Pro 400	Dietary supplement: Beetroot juice; Participants will take on dose in the morning and one in the afternoon, for 7 days during their final academic examinations; Other Names: Beet-it 400
Active Comparator: One active dose of beetroot juice and one placebo dose of beetroot juice; 1 active (nitrate containing) dose of Beet-it Pro 400 and one placebo (nitrate-depleted) dose of beetroot juice	Dietary supplement: Beetroot juice; Participants will take on dose in the morning and one in the afternoon, for 7 days during their final academic examinations; Other Names: Beet-it 400
Placebo Comparator: Two placebo doses of beetroot juice; 2 placebo (nitrate-depleted) doses of beetroot juice	Dietary supplement: Beetroot juice; Participants will take on dose in the morning and one in the afternoon, for 7 days during their final academic examinations; Other Names: Beet-it 400

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exhaled Nitric Oxide	The Fraction of NO in Exhaled Breath (FENO, in ppb) will be measured with an electrochemical gas analyzer (NIOX vero).	Baseline (non-stress mid point of semester), 1-3 days into active beetroot shots (during final examination period), 4-6 days into active beetroot shots (during final examination period)
Viral Polymerase Chain Reaction	Binary positive/negative test results for a panel of viral and bacterial respiratory pathogens.	Baseline (non-stress mid point of semester), 4-6 days into active beetroot shots (during final examination period)
Wisconsin Upper Respiratory Symptom Survey (WURSS)	Assess symptoms of acute upper respiratory tract infections (common cold symptoms) by questionnaire	Baseline (non-stress mid point of semester), 1-3 days into active beetroot shots (during final examination period), 4-6 days into active beetroot shots (during final examination period), 1-3 days after finishing beetroot shots (after final examinations)
Adherence monitoring (feasibility)	Participants will upload a cell phone video of their intake for that day to a secure cloud folder, time stamp in comparison to assigned intake windows provides measure of adherence	Every day during active beetroot shots (Days 1-7)
Burdensomeness	Follow-up questionnaire will be administered with the online follow-up survey. It explores experience with the best mode of reminder receipt (email or text message), whether the participants guessed their condition, and how burdensome 8 aspects of the study (including daily intake, video recording, upload, questionnaires, physiological assessment) were.	1-3 days after finishing beetroot shots (after final examinations)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute stress	Ad-hoc acute stress rating	Baseline (non-stress mid point of semester), 1-3 days into active beetroot shots (during final examination period), 4-6 days into active beetroot shots (during final examination period), 1-3 days after finishing beetroot shots (after final examinations)
Cortisol	Cortisol, from saliva sampled with passive drool test	Baseline (non-stress mid point of semester), 1-3 days into active beetroot shots (during final examination period), 4-6 days into active beetroot shots (during final examination period)
Perceived stress	Perceived Stress Scale (PSS)	Baseline (non-stress mid point of semester), 4-6 days into active beetroot shots (during final examination period)
Mood	Hospital Anxiety and Depression Scale (HADS)	Baseline (non-stress mid point of semester), 4-6 days into active beetroot shots (during final examination period)
Blood pressure (systolic and diastolic blood pressure) and heart rate	Measured after at least 10 min of acclimatization to the laboratory	Baseline (non-stress mid point of semester), 1-3 days into active beetroot shots (during final examination period), 4-6 days into active beetroot shots (during final examination period)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
One-day Food Record	One-day food record via the Automated Self-Administered 24-Hour platform; control variable	Baseline (non-stress mid point of semester), 1-3 days into active beetroot shots (during final examination period), 4-6 days into active beetroot shots (during final examination period)
Arginase	From Exhaled breath condensate or saliva, competitors/inhibitor of NO; exploratory mediator of FENO	Baseline (non-stress mid point of semester), 1-3 days into active beetroot shots (during final examination period), 4-6 days into active beetroot shots (during final examination period)
Asymmetric dimethylarginine	From Exhaled breath condensate or saliva, competitors/inhibitor of NO; exploratory mediator of FENO	Baseline (non-stress mid point of semester), 1-3 days into active beetroot shots (during final examination period), 4-6 days into active beetroot shots (during final examination period)

Collaborators and Investigators

• Sponsor: Southern Methodist University
• Collaborators: Baylor University
• Investigators: Principal Investigator: Thomas Ritz, Ph.D., Southern Methodist University; Study Director: Annie Ginty, Ph.D., Baylor University

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2024
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 15, 2026

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: May 10, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 10, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Respiratory Tract Infections
• Other Study ID Numbers: 23-108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No