HealthyPhase 1NCT04588740
Inorganic Nitrate: Sex Differences in Muscle Contractile Function and Efficiency
A Phase 1 study testing concentrated beet root juice in people with Healthy, run by University of Virginia at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 34 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- concentrated beet root juice
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jan 2020to 30 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 34 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- • 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22903
About this study
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.
Read the detailed description
Dietary inorganic nitrate 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. The amount of research investigating the effects of beet root juice supplementation (which contains a high concentration of inorganic nitrate) on exercise responses has increased dramatically in the last 10 years-with over 150 studies in the literature. To date there are only 7 studies looking at exercise responses following inorganic nitrate supplementation specifically in females. Given the physiological differences between males and females studies looking into sex-differences and the specific sex-response are warranted.
The purpose of this study is to investigate whether dietary nitrate supplementation has different effects on muscle contractile function in males and females. We will assess muscle function during an isokinetic protocol where subjects will have to produce maximum efforts at three different torque development speeds (i.e. 180, 270 and 360). This will be followed with a fatigue protocol which will consist of intermittent voluntary contractions at 60% of their maximal voluntary contraction until exhaustion provided by research in the Sport Medicine - Kinesiology department. Thus, we will be able to distinguish the effect of dietary nitrate on contractile function and its capacity to delay fatigue in a sex-specific manner.
The hypothesis of this study is that there will be a group difference between males and females for change in peak power and time to exhaustion after consuming dietary nitrate (in the form of concentrated beetroot juice) for 5 days.
In order to test this hypothesis, we will recruit 24 healthy recreationally active individuals (12 females + 12 males) in a randomized, double-blind, placebo controlled, cross over design.
Specific Aim 1: Determine the sex-differences of the effect of dietary nitrate supplementation on peak power. We hypothesize that the males will have larger improvement in peak power following dietary nitrate.
Specific Aim 2: Determine the sex-differences of the effect of dietary nitrate on fatigue during an intermittent isometric fatigue protocol. We hypothesize that the females will have a greater improvement in fatigue resistance than males.
Specific Aim 3: Determine the sex-differences of the effect of dietary nitrate on oxygen consumption during sub maximal exercise.
- Conditions
- Healthy
- Being tested
- concentrated beet root juice, Placebo beet root juice
- Keywords
- exercise, beet root juice, dietary nitrate, nitric oxide
- Medical subject headings
- Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
concentrated beet root juiceDrug
Also called dietary inorganic nitrate
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.
Placebo beet root juiceDrug
Also called placebo
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)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo beet root juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Treatment differences (BR v PL) and sex differences (females vs males) in exercise economy (i.e. oxygen consumption) during a submaximal exercise bout (i.e. 75% Gas exchange threshold).
Measured: 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
Treatment differences (BR v PL) and sex differences (females vs males) in exercise capacity during a constant work rate (i.e. 70% delta) tested on a cycle ergometer.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2020
- Study start20 Jan 2020
- Primary completion30 Dec 2023
- Study completion30 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jason Allen, University of Virginia
- Investigators
- Jason D. Allen, PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04588740
- Sponsor's protocol ID
- 21983
- Status last verified
- May 2024
- First submitted
- 1 Oct 2020
- Last updated
- 8 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this RCT, after deidentification (text, tables, figures, and appendices).
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inorganic Nitrate: Sex Differences in Muscle Contractile Function and Efficiency
- ClinicalTrials.gov ID
- NCT04588740
- Acronym / sponsor ID
- 21983
- Conditions
- Healthy
- Keywords
- exercise, beet root juice, dietary nitrate, nitric oxide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 20 Jan 2020 (actual)
- Primary completion
- 30 Dec 2023 (actual)
- Study completion
- 30 Dec 2023 (actual)
- First posted
- 19 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Dietary inorganic nitrate 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. The amount of research investigating the effects of beet root juice supplementation (which contains a high concentration of inorganic nitrate) on exercise responses has increased dramatically in the last 10 years-with over 150 studies in the literature. To date there are only 7 studies looking at exercise responses following inorganic nitrate supplementation specifically in females. Given the physiological differences between males and females studies looking into sex-differences and the specific sex-response are warranted.
The purpose of this study is to investigate whether dietary nitrate supplementation has different effects on muscle contractile function in males and females. We will assess muscle function during an isokinetic protocol where subjects will have to produce maximum efforts at three different torque development speeds (i.e. 180, 270 and 360). This will be followed with a fatigue protocol which will consist of intermittent voluntary contractions at 60% of their maximal voluntary contraction until exhaustion provided by research in the Sport Medicine - Kinesiology department. Thus, we will be able to distinguish the effect of dietary nitrate on contractile function and its capacity to delay fatigue in a sex-specific manner.
The hypothesis of this study is that there will be a group difference between males and females for change in peak power and time to exhaustion after consuming dietary nitrate (in the form of concentrated beetroot juice) for 5 days.
In order to test this hypothesis, we will recruit 24 healthy recreationally active individuals (12 females + 12 males) in a randomized, double-blind, placebo controlled, cross over design.
Specific Aim 1: Determine the sex-differences of the effect of dietary nitrate supplementation on peak power. We hypothesize that the males will have larger improvement in peak power following dietary nitrate.
Specific Aim 2: Determine the sex-differences of the effect of dietary nitrate on fatigue during an intermittent isometric fatigue protocol. We hypothesize that the females will have a greater improvement in fatigue resistance than males.
Specific Aim 3: Determine the sex-differences of the effect of dietary nitrate on oxygen consumption during sub maximal exercise.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dietary nitrate | Active comparator | Drug: concentrated beet root juiceThe 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. |
| Placebo | Placebo comparator | Drug: Placebo beet root juiceThe placebo beet root juice is made by the same company (BEET IT, James White Drinks, Ipswich, UK) and contains no inorganic nitrate. |
Who may qualify
- Ages
- 18 to 34 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (11 listed)
- • Known pulmonary, cardiovascular or metabolic disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| concentrated beet root juiceAlso: dietary inorganic nitrateOn 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. | Drug | Dietary nitrate |
| Placebo beet root juiceAlso: placeboThis 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) | Drug | Placebo |
Primary outcome
Muscle function - Maximal knee extensor speed and power determined using isokinetic dynamometry
Time frame: 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.
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.
2 secondary outcomes
Oxygen consumption during a submaximal exercise
Time frame: 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
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this RCT, after deidentification (text, tables, figures, and appendices).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason D. Allen, PhD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing concentrated beet root juice in people with Healthy, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Muscle function - Maximal knee extensor speed and power determined using isokinetic dynamometry (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.