Clinical trial NCT06416228: Beetroot Juice NO Cold Study
Official title: Beetroot Juice Supplement for Boosting Mucosal Immunity - The NO Cold Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Respiratory Tract Infections
Cold Symptoms
Exhaled Nitric Oxide
Lead sponsor: Southern Methodist University
Sponsor class: OTHER
Collaborators: name: Baylor University
First posted: 2024-05-16
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blinded, placebo controlled study
Primary purpose: PREVENTION

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Exhaled Nitric Oxide
timeFrame: 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)
measure: Viral Polymerase Chain Reaction
timeFrame: Baseline (non-stress mid point of semester), 4-6 days into active beetroot shots (during final examination period)
measure: Wisconsin Upper Respiratory Symptom Survey (WURSS)
timeFrame: 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)
measure: Adherence monitoring (feasibility)
timeFrame: Every day during active beetroot shots (Days 1-7)
measure: Burdensomeness
timeFrame: 1-3 days after finishing beetroot shots (after final examinations)
Secondary outcomes:
measure: Acute stress
timeFrame: 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)
measure: Cortisol
timeFrame: 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)
measure: Perceived stress
timeFrame: Baseline (non-stress mid point of semester), 4-6 days into active beetroot shots (during final examination period)
measure: Mood
timeFrame: Baseline (non-stress mid point of semester), 4-6 days into active beetroot shots (during final examination period)
measure: Blood pressure (systolic and diastolic blood pressure) and heart rate
timeFrame: 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 outcomes:
measure: One-day Food Record
timeFrame: 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)
measure: Arginase
timeFrame: 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)
measure: Asymmetric dimethylarginine
timeFrame: 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)
Locations:
city: Dallas
country: United States
facility: Southern Methodist University
state: Texas
city: Waco
country: United States
facility: Baylor University
state: Texas
Study officials:
affiliation: Southern Methodist University
name: Thomas Ritz, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor University
name: Annie Ginty, Ph.D.
role: STUDY_DIRECTOR
References: