AgingPhase 1NCT03595774
Dose-response Effect of Dietary Nitrate on Muscle Function in Older Individuals
A Phase 1 study testing Beet root juice in people with Aging and Sarcopenia, run by Indiana University at 1 site in United States.
Trial summary
Nitrate is a naturally-occurring substance found in foods, especially green leafy vegetables and beets. Increasing nitrate intake (by drinking beetroot juice (BRJ) has been shown to improve muscle function young and middle-aged subjects, athletes, and patients with heart failure. Read more about this study
- Who is it for?
- Ages 65 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging, Sarcopenia
- What is being tested?
- Beet root juice
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2018to 31 Jul 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 to 79 years
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- In good health, as determined by the investigator's review of history (provided by subject at screening visit), physical examination, and routine blood and urine tests (done at screening visit)
Who cannot join
- Men and women <65 or >79 years of age
- Unable to provide informed consent
- Currently pregnant or lactating (given the age range for the study, verbal confirmation by subject is believed to be sufficient)
- Current smokers
- Significant orthopedic limitations or other contraindications to strenuous exercise
- Those taking phosphodiesterase inhibitors (e.g., Viagra)
Show all 9Show fewer
- Those taking proton pump inhibitors, antacids, xanthine oxidase inhibitors, or on hormone replacement therapy
- Those taking anti-coagulants (e.g., Coumadin) or on anti-platelet therapy
- History of neuromuscular disease (e.g., cervical spondylotic radiculomyelpathy, lumbar spondylosis, amyotrophic lateral sclerosis, Guillain-Barré syndrome, and acquired demyelinating polyneuropathies), cardiovascular disease (e.g., > stage I hypertension, heart failure, myocardial infarction/ischemia, significant myocardial or pericardial diseases (e.g. amyloidosis, constriction), moderate or severe valvular disease, renal disease, liver disease, or anemia
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana University School of Health and Human Sciences
Indianapolis, Indiana, 46202
About this study
Nitrate is a naturally-occurring substance found in foods, especially green leafy vegetables and beets. Increasing nitrate intake (by drinking beetroot juice (BRJ) has been shown to improve muscle function young and middle-aged subjects, athletes, and patients with heart failure. The purpose of this study is to determine whether dietary nitrate provides a similar benefit in older individuals, and if so, the optimal dose. We will be comparing the effects of ingesting BRJ containing a smaller or greater amount of nitrate versus the effects of a placebo (BRJ from which the nitrate has been removed).
Read the detailed description
This study consists of four visits that will take a minimum of 15 days to complete.
Study Visit One (Screening) 1-2 hours The purpose of the screening visit is to explain all aspects of the study. The investigators will also determine if individuals can participate in the study. Eligible subjects will undergo a complete medical history and physical exam. They will have their blood drawn, and will provide a urine sample (to determine if they are pregnant). Subjects will also practice the entire neuromuscular function exercise test. During this test, the strength of the subject's muscles will be determined by having them kick, push and/or pull back as hard as they can while their leg is strapped to an exercise device. Blood pressure and heart rate and rhythm will be monitored.
Subjects will be instructed to consume their normal diet throughout the study. However, they will be asked to avoid eating foods high in nitrate such as beets, spinach, and collard greens the evening before each visit. They will be asked to refrain from the use of antibacterial mouthwash, such as Listerine or Cepacol, during the study. Subjects will also be asked to not chew gum or to consume alcohol or food and drinks that contain caffeine for 24 hour before each visit. This includes coffee, tea, chocolate and soft drinks such as Mountain Dew. Finally, they will be asked to fast for 12 hour prior to each study visit.
Study Visit Two - Approximately 5 hours At the beginning of this visit a catheter (small, flexible, sterile plastic tube) will be placed through a vein in one of the subject's arms. This is for collection of blood samples. Blood will be drawn four times during this visit. Each draw will be 6mL or about 1.2 teaspoons. The first blood draw will check nitrate and nitrogen levels. Subjects will then have a breath test to check nitric oxide. They will then drink about 280 mL (about 1 cup) of BRJ. In one trial, this will be a placebo, that is, BRJ from which the essentially all of the nitrate has been removed. In another trial, they will drink BRJ still containing nitrate. In a third trial, they will drink an equal mixture of the placebo and nitrate-containing BRJ. Blood and breath samples will be obtained every hour. Heart rate and blood pressure will be measured at the same times the blood and breath samples are obtained. About 2 hours after ingestion of BRJ (or placebo) subjects will be asked to perform the neuromuscular function test that was practiced during the screening visit. After completing the exercise test one final blood and breath sample will be obtained.
Study Visits Three and Four
The same procedures completed during Study Visit Two will be performed. The order of treatment (placebo vs. lower dose vs. higher dose of nitrate) will be randomized using a computer program. Neither the subjects nor the investigators will know the treatment they receive during each visit until the entire study is completed.
- Conditions
- Aging, Sarcopenia
- Being tested
- Beet root juice
- Keywords
- nitric oxide
- Medical subject headings
- Sarcopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beet root juiceDietary supplement
Also called Beet It Sport Nitrate 400
Beet root juice
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 3.3 mL/kg concentrated beet root juice *depleted of nitrate* Other names: Beet It Sport Nitrate 400 placebo Receives: Dietary Supplement: Beet root juice |
| low nitrate | Active comparator | 1.55 mL/kg concentrated beet root juice depleted of nitrate + 1.55 mL/kg concentrated beet root juice *depleted of nitrate*
Other names: Beet It Sport Nitrate 400 placebo + Beet It Sport Nitrate 400 Receives: Dietary Supplement: Beet root juice |
| high nitrate | Active comparator | 3.3 mL/kg concentrated beet root juice containing nitrate
Other names:Beet It Sport Nitrate 400 Receives: Dietary Supplement: Beet root juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal Knee Extensor Velocity
Maximal knee extensor velocity determined using isokinetic dynamometry
Measured: 1 day
Maximal Knee Extensor Power
Maximal knee extensor power determined using isokinetic dynamometry
Measured: 1 day
Secondary outcomes (3)
Plasma Nitrite
Measured: 0, 1, 2, 3 h after ingestion
Plasma Nitrate
Measured: 0, 1, 2, 3 h after ingestion
Breath Nitric Oxide
Measured: 0, 1, 2, 3 h after ingestion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2018
- Study start1 Sep 2018
- Primary completion31 Jul 2021
- Study completion31 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blind, placebo-controlled, crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrew Coggan, Indiana University
- Investigators
- Andrew R Coggan, PhD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03595774
- Sponsor's protocol ID
- 1712606816
- Status last verified
- Feb 2024
- First submitted
- 11 Jul 2018
- Last updated
- 29 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Coggan AR. Dietary Nitrate and Muscle Function in Humans: Acute versus Chronic Mechanisms. Med Sci Sports Exerc. 2018 Apr;50(4):874. doi: 10.1249/MSS.0000000000001489. No abstract available.
PubMed 29547495Coggan AR, Broadstreet SR, Mahmood K, Mikhalkova D, Madigan M, Bole I, Park S, Leibowitz JL, Kadkhodayan A, Thomas DP, Thies D, Peterson LR. Dietary Nitrate Increases VO2peak and Performance but Does Not Alter Ventilation or Efficiency in Patients With Heart Failure With Reduced Ejection Fraction. J Card Fail. 2018 Feb;24(2):65-73. doi: 10.1016/j.cardfail.2017.09.004. Epub 2017 Sep 12.
PubMed 28916479Coggan AR, Peterson LR. Dietary Nitrate and Skeletal Muscle Contractile Function in Heart Failure. Curr Heart Fail Rep. 2016 Aug;13(4):158-65. doi: 10.1007/s11897-016-0293-9.
PubMed 27271563Rimer EG, Peterson LR, Coggan AR, Martin JC. Increase in Maximal Cycling Power With Acute Dietary Nitrate Supplementation. Int J Sports Physiol Perform. 2016 Sep;11(6):715-720. doi: 10.1123/ijspp.2015-0533. Epub 2016 Aug 24.
PubMed 26641379Coggan AR, Leibowitz JL, Spearie CA, Kadkhodayan A, Thomas DP, Ramamurthy S, Mahmood K, Park S, Waller S, Farmer M, Peterson LR. Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial. Circ Heart Fail. 2015 Sep;8(5):914-20. doi: 10.1161/CIRCHEARTFAILURE.115.002141. Epub 2015 Jul 15.
PubMed 26179185Coggan AR, Leibowitz JL, Kadkhodayan A, Thomas DP, Ramamurthy S, Spearie CA, Waller S, Farmer M, Peterson LR. Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women. Nitric Oxide. 2015 Aug 1;48:16-21. doi: 10.1016/j.niox.2014.08.014. Epub 2014 Sep 6.
PubMed 25199856
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose-response Effect of Dietary Nitrate on Muscle Function in Older Individuals
- ClinicalTrials.gov ID
- NCT03595774
- Acronym / sponsor ID
- 1712606816
- Conditions
- Aging, Sarcopenia
- Keywords
- nitric oxide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 31 Jul 2021 (actual)
- Study completion
- 31 Jul 2021 (actual)
- First posted
- 23 Jul 2018 (actual)
- Results
- Posted 29 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Nitrate is a naturally-occurring substance found in foods, especially green leafy vegetables and beets. Increasing nitrate intake (by drinking beetroot juice (BRJ) has been shown to improve muscle function young and middle-aged subjects, athletes, and patients with heart failure. The purpose of this study is to determine whether dietary nitrate provides a similar benefit in older individuals, and if so, the optimal dose. We will be comparing the effects of ingesting BRJ containing a smaller or greater amount of nitrate versus the effects of a placebo (BRJ from which the nitrate has been removed).
Detailed description
This study consists of four visits that will take a minimum of 15 days to complete.
Study Visit One (Screening) 1-2 hours The purpose of the screening visit is to explain all aspects of the study. The investigators will also determine if individuals can participate in the study. Eligible subjects will undergo a complete medical history and physical exam. They will have their blood drawn, and will provide a urine sample (to determine if they are pregnant). Subjects will also practice the entire neuromuscular function exercise test. During this test, the strength of the subject's muscles will be determined by having them kick, push and/or pull back as hard as they can while their leg is strapped to an exercise device. Blood pressure and heart rate and rhythm will be monitored.
Subjects will be instructed to consume their normal diet throughout the study. However, they will be asked to avoid eating foods high in nitrate such as beets, spinach, and collard greens the evening before each visit. They will be asked to refrain from the use of antibacterial mouthwash, such as Listerine or Cepacol, during the study. Subjects will also be asked to not chew gum or to consume alcohol or food and drinks that contain caffeine for 24 hour before each visit. This includes coffee, tea, chocolate and soft drinks such as Mountain Dew. Finally, they will be asked to fast for 12 hour prior to each study visit.
Study Visit Two - Approximately 5 hours At the beginning of this visit a catheter (small, flexible, sterile plastic tube) will be placed through a vein in one of the subject's arms. This is for collection of blood samples. Blood will be drawn four times during this visit. Each draw will be 6mL or about 1.2 teaspoons. The first blood draw will check nitrate and nitrogen levels. Subjects will then have a breath test to check nitric oxide. They will then drink about 280 mL (about 1 cup) of BRJ. In one trial, this will be a placebo, that is, BRJ from which the essentially all of the nitrate has been removed. In another trial, they will drink BRJ still containing nitrate. In a third trial, they will drink an equal mixture of the placebo and nitrate-containing BRJ. Blood and breath samples will be obtained every hour. Heart rate and blood pressure will be measured at the same times the blood and breath samples are obtained. About 2 hours after ingestion of BRJ (or placebo) subjects will be asked to perform the neuromuscular function test that was practiced during the screening visit. After completing the exercise test one final blood and breath sample will be obtained.
Study Visits Three and Four
The same procedures completed during Study Visit Two will be performed. The order of treatment (placebo vs. lower dose vs. higher dose of nitrate) will be randomized using a computer program. Neither the subjects nor the investigators will know the treatment they receive during each visit until the entire study is completed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Double-blind, placebo-controlled, crossover
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Dietary Supplement: Beet root juice3.3 mL/kg concentrated beet root juice *depleted of nitrate* Other names: Beet It Sport Nitrate 400 placebo |
| low nitrate | Active comparator | Dietary Supplement: Beet root juice1.55 mL/kg concentrated beet root juice depleted of nitrate + 1.55 mL/kg concentrated beet root juice *depleted of nitrate* Other names: Beet It Sport Nitrate 400 placebo + Beet It Sport Nitrate 400 |
| high nitrate | Active comparator | Dietary Supplement: Beet root juice3.3 mL/kg concentrated beet root juice containing nitrate Other names:Beet It Sport Nitrate 400 |
Who may qualify
- Ages
- 65 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (1 listed)
- In good health, as determined by the investigator's review of history (provided by subject at screening visit), physical examination, and routine blood and urine tests (done at screening visit)
Key exclusion criteria (9 listed)
- Men and women <65 or >79 years of age
- Unable to provide informed consent
- Currently pregnant or lactating (given the age range for the study, verbal confirmation by subject is believed to be sufficient)
- Current smokers
- Significant orthopedic limitations or other contraindications to strenuous exercise
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 |
|---|---|---|
| Beet root juiceAlso: Beet It Sport Nitrate 400Beet root juice | Dietary supplement | Placebo, high nitrate, low nitrate |
Primary outcome
Maximal Knee Extensor Velocity
Time frame: 1 day
Maximal knee extensor velocity determined using isokinetic dynamometry
Maximal Knee Extensor Power
Time frame: 1 day
Maximal knee extensor power determined using isokinetic dynamometry
3 secondary outcomes
Plasma Nitrite
Time frame: 0, 1, 2, 3 h after ingestion
Plasma Nitrate
Time frame: 0, 1, 2, 3 h after ingestion
Breath Nitric Oxide
Time frame: 0, 1, 2, 3 h after ingestion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29547495Coggan AR. Dietary Nitrate and Muscle Function in Humans: Acute versus Chronic Mechanisms. Med Sci Sports Exerc. 2018 Apr;50(4):874. doi: 10.1249/MSS.0000000000001489. No abstract available.
- Background: PubMed 28916479Coggan AR, Broadstreet SR, Mahmood K, Mikhalkova D, Madigan M, Bole I, Park S, Leibowitz JL, Kadkhodayan A, Thomas DP, Thies D, Peterson LR. Dietary Nitrate Increases VO2peak and Performance but Does Not Alter Ventilation or Efficiency in Patients With Heart Failure With Reduced Ejection Fraction. J Card Fail. 2018 Feb;24(2):65-73. doi: 10.1016/j.cardfail.2017.09.004. Epub 2017 Sep 12.
- Background: PubMed 27271563Coggan AR, Peterson LR. Dietary Nitrate and Skeletal Muscle Contractile Function in Heart Failure. Curr Heart Fail Rep. 2016 Aug;13(4):158-65. doi: 10.1007/s11897-016-0293-9.
- Background: PubMed 26641379Rimer EG, Peterson LR, Coggan AR, Martin JC. Increase in Maximal Cycling Power With Acute Dietary Nitrate Supplementation. Int J Sports Physiol Perform. 2016 Sep;11(6):715-720. doi: 10.1123/ijspp.2015-0533. Epub 2016 Aug 24.
- Background: PubMed 26179185Coggan AR, Leibowitz JL, Spearie CA, Kadkhodayan A, Thomas DP, Ramamurthy S, Mahmood K, Park S, Waller S, Farmer M, Peterson LR. Acute Dietary Nitrate Intake Improves Muscle Contractile Function in Patients With Heart Failure: A Double-Blind, Placebo-Controlled, Randomized Trial. Circ Heart Fail. 2015 Sep;8(5):914-20. doi: 10.1161/CIRCHEARTFAILURE.115.002141. Epub 2015 Jul 15.
- Background: PubMed 25199856Coggan AR, Leibowitz JL, Kadkhodayan A, Thomas DP, Ramamurthy S, Spearie CA, Waller S, Farmer M, Peterson LR. Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women. Nitric Oxide. 2015 Aug 1;48:16-21. doi: 10.1016/j.niox.2014.08.014. Epub 2014 Sep 6.
- Individual participant dataSharing planned: No
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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.
Andrew R Coggan, PhD principal investigator
Indiana University
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 Beet root juice in people with Aging and Sarcopenia, run by Indiana University 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 1 inclusion and 9 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 29 Jul 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?
Yes. Results are posted in the registry (first posted 29 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximal Knee Extensor Velocity (time frame: 1 day). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03595774, which also lists 6 linked publications.
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 29 Jul 2024.