Inorganic Nitrate: Sex Differences in Muscle Contractile Function and Efficiency

NCT04588740 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 21983
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Dietary inorganic nitrate, in the form of beet root juice, is a nutritional intervention, considered to be an exercise enhancer due to its capacity to increase Nitric Oxide (NO) bioavailability. Increasing NO bioavailability has been associated with improved mitochondrial respiration, muscle tissue perfusion and contractile function which may lead to improved exercise capacity. However, the majority of the literature is on male subjects. This limits the applicability of this supplement in females. Therefore, our project aims to determine sex-differences and the specific sex-response across the menstrual cycle of dietary nitrate supplementation on exercise efficiency, strength and fatigue resistance.

Conditions

Healthy

Keywords

exercise; beet root juice; dietary nitrate; nitric oxide

Outcome Measures

Primary Outcomes (1)

• Muscle function - Maximal knee extensor speed and power determined using isokinetic dynamometry

  This is an isokinetic (same speed over range of motion) strength test that will measure peak torque of the quadricep and hamstring (Nm/kg) and average power (W/kg). The testing protocol will be completed at three different speeds 180degrees/second, 270degrees/second and 360degrees/second.

  Male subjects (2 occasions)- It will be measured on day 5 of supplementation (placebo or nitrate). Female subjects (4 times) - It will be measured between days 3-5 and 10-15 of their menstrual cycle in two different cycles.

Secondary Outcomes (2)

• Oxygen consumption during a submaximal exercise

  Male subjects (2 occasions)- It will be measured on day 5 of supplementation (placebo or nitrate). Female subjects (4 times) - It will be measured between days 3-5 and 10-15 of their menstrual cycle in two different cycles.

• Time to exhaustion during a high intensity exercise bout on a cycle ergometer

  Male subjects (2 occasions)- It will be measured on day 5 of supplementation (placebo or nitrate). Female subjects (4 times) - It will be measured between days 3-5 and 10-15 of their menstrual cycle in two different cycles.

Study Arms (2)

Dietary nitrate

ACTIVE COMPARATOR

The active treatment, beetroot juice (BEET IT, James White Drinks, Ipswich, UK), contains 6.2mmol of inorganic nitrate. Participants will continue supplementation until they complete all testing visits.

Drug: concentrated beet root juice

Placebo

PLACEBO COMPARATOR

The placebo beet root juice is made by the same company (BEET IT, James White Drinks, Ipswich, UK) and contains no inorganic nitrate.

Drug: Placebo beet root juice

Interventions

concentrated beet root juice DRUG

On average, we will expect subjects to ingest the supplement for approximately 5 days minimum depending on their testing schedule. On each testing day subjects will be asked to consume the two bottles of either beetroot juice (BRJ) or Placebo 2.5 hours before testing time. Specifically, for female subjects, they will be asked to start their supplementation on day 1 of menses. On day 3-4 they will take the last 2 shots. Female subjects' wash-out period will go according to their menstrual cycle as we will be controlling for hormone fluctuation (low vs high estrogen phase) know to interact with nitric oxide physiology.

Also known as: dietary inorganic nitrate

Dietary nitrate

Placebo beet root juice DRUG

This will follow the same supplementation regime as explained above but this supplement taste and looks exactly the same as the nitrate-rich beet root juice. It is provided by the same company that produces the concentrated beet root juice shots (Beet It, UK)

Also known as: placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 34 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female participants in good general health as assessed by the standard procedures described below and specifically meeting normal blood pressure range (systolic: 120-129, diastolic: 80-84) and normal BMI range (18.5-24.9)
• Engaged in physical activity and/or recreational sport but not highly-trained, as assessed by the investigator in personal consultation and laboratory stress test.
• No orthopedic limitations.

You may not qualify if:

• Known pulmonary, cardiovascular or metabolic disease
• Food allergies including phenylketonurea (PKU)
• Regular use of dietary supplements within 6 months prior to the start of the study
• Taking any dietary/sport supplements that could affect nitrate metabolism: Sport supplements containing the amino acids L-arginine, L-citrulline, beta-alanine, Creatine, Nitrate based pre-work out supplements
• Blood donation within 3 months prior to the start of the study
• Substance abuse within 2 years of the start of the study
• Smokers
• Hyper- or hypotension medication
• Pregnant or lactating
• Not having a regular menstrual cycle (minimum of 10-12 menses per year)
• Stopped using a contraceptive method or started a new contraceptive method within 3 months.

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

MeSH Terms

Conditions

Motor Activity

Condition Hierarchy (Ancestors)

Behavior

Study Officials

• Jason D. Allen, PhD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a randomized, double-blind, placebo-controlled, cross-over design. This means that all subjects will complete both supplementation phases in a randomized order.

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: October 19, 2020
• Study Start: January 20, 2020
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2023
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Beginning 9 months and ending 36 months following article publication.

Locations

US (1)