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Dietary Nitrate and Muscle Power With Aging

Dietary Nitrate and Muscle Power With Aging

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03513302
Enrollment
47
Registered
2018-05-01
Start date
2019-03-01
Completion date
2022-08-30
Last updated
2025-02-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Aging, Sarcopenia

Keywords

nitric oxide

Brief summary

The purpose of this study is to see if drinking beetroot juice (BRJ) is beneficial for aging patients. We hope to determine the effect of BRJ on exercise performance. BRJ improves exercise performance in athletes and normal people. We are trying to determine if BRJ improves exercise performance in aging patients. We will be comparing the effects of BRJ versus the effects of a placebo (BRJ without the nitrates that are naturally occurring in beets and other similar foods). It is thought that the benefits of BRJ may come from its natural nitrate content. Although BRJ is available for purchase in grocery stores, for the purposes of this study it is considered investigational, which means that it has not been approved as a medical therapy.

Detailed description

This study consists of two parts separated by a 14 day wash-out. Subjects will be randomly assigned to receive either the BRJ or placebo during the first part. During the second part they will receive the opposite of what they had during the first part. This is considered a double-blind study, which means neither the subjects nor the investigators will know what form (BRJ or placebo) a subject is receives. Study Visit One (Screening) 1-2 hours The purpose of the screening visit is to explain all aspects of the study. It will also determine if subjects can participate in the study. Subjects will provide a complete medical history and undergo a physical exam. They will have their blood drawn (about 1.5 teaspoons) and provide a urine sample. They will also practice the entire neuromuscular function exercise test. During this test, the strength of their muscles will be determined by having them kick, push and/or pull back as hard as you can while their leg is strapped to an exercise device. A vital signs monitor will measure your blood pressure, heart rate, and rhythm. During the remainder of the study subjects will be instructed to consume their normal diet. 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. Chewing gum, alcohol, and food and drinks containing caffeine (coffee, tea, chocolate, and soft drinks) should be avoided 24 hours prior to each visit. 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 6 mL or about 1.2 teaspoons. The first blood draw will check nitrate and nitrite levels. They will then have a breath test to check nitric oxide. They will then drink 140 mL (about 2/3 of a cup) of BRJ (or placebo). 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. Subjects will then rest quietly in a private room for about 2 hours after ingestion of BRJ (or placebo) then will perform: * The neuromuscular function test that was practiced during the screening visit. * After completing the exercise test they will undergo a muscle biopsy of their thigh muscle. First, the area will be sterilized and numbed with an injection. Next, a small incision (about ¼ inch) will be made and a small biopsy needle will be used to collect a small sample of your muscle (about the size of a pencil eraser). This will be performed on the leg opposite of that used during the neuromuscular test. * One final blood and breath sample will then be obtained. * Subjects will then be provided a 7 day supply of BRJ (or placebo) and will continue to drink two bottles (about 5 oz) every morning. * Subjects will also be provided with an activity tracker. This will be worn at the hip during all waking hours except when bathing or swimming. This monitor will measure total activity time and sedentary time. Study Visit Three - 1-2 hours Subjects will return to the research center with the empty BRJ bottles. At this visit a single blood (1.2 teaspoon) and breath sample will be collected. Subjects will then complete a questionnaire to rate how tired they felt during the previous week. They will be provided another 7 day supply of BRJ (or placebo) and will continue to drink two bottles every morning. Study Visit Four - Approximately 5 hours Subjects will return to the research center and undergo the same procedures as they did in Study Visit Two. They will also complete a questionnaire that will rate how tired they felt during the previous week. Washout After visit four subjects will undergo a 14 day washout period where they will not drink the BRJ (or placebo). There are no dietary restrictions at this time; subjects may consume caffeine, alcohol, gum, mouthwash, etc. Subjects will then repeat Study Visits Two, Three, and Four again. However, during this they will be given the opposite form of BRJ you had received before. Study Visit Five Subjects will repeat the procedures completed during Study Visit Two. Study Visit Six Subjects will repeat the procedures completed during Study Visit Three. Study Visit Seven Subjects will repeat the procedures completed during Study Visit Four.

Interventions

DIETARY_SUPPLEMENTplacebo

2 x 70 mL concentrated beet root juice depleted of nitrate per day for 14 days.

DIETARY_SUPPLEMENTnitrate

2 x 70 mL concentrated beet root juice per day for 14 days.

Sponsors

Indiana University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)

Intervention model description

Double-blind, placebo-controlled, crossover

Eligibility

Sex/Gender
ALL
Age
65 Years to 79 Years
Healthy volunteers
Yes

Inclusion criteria

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)

Exclusion criteria

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) * 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

Design outcomes

Primary

MeasureTime frameDescription
Maximal Knee Extension Velocity1 day\*Maximal\* knee extension velocity was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 radians per second on an isokinetic dynamometer (device that controls velocity while measuring torque). Peak power at each velocity was calculated by multiplying the measured torque by that velocity, then a parabolic function was fit to these calculated data to predict \*maximal\* knee extensor velocity. Higher values are better.
Muscle Knee Extensor Power1 dayThis outcome was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 radians per second on an isokinetic dynamometer (device that controls velocity while measuring torque). \*Peak\* power at each velocity was calculated by multiplying the measured torque by that velocity, then a parabolic function was fit to these calculated data to predict \*maximal\* knee extensor power. Higher values are better.
Maximal Knee Extension Power14 days\*Maximal\* knee extension power was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 rad/s on an isokinetic dynamometer (device that controls velocity while measuring torque). \*Peak\* power at each velocity was calculated by multiplying the measured torque by that velocity, then \*maximal\* power was determined by fitting a parabolic function to these data. Higher values are better.

Other

MeasureTime frameDescription
Plasma Nitrate0,1,2,3 hours after treatment at 1 dayPlasma nitrate concentrations were measured using high performance liquid chromatography.
Physical Function1,14 days of treatmentPatient-Reported Outcomes Measurement Information System physical function questionnaire (PROMIS 20a). Results given as T-score with mean of 50 and standard deviation of 10. Higher is better.
Plasma Nitrite0,1,2,3 hours after treatment at 1 dayPlasma nitrite concentrations were measured using high performance liquid chromatography.
Perceived Fatigue1 and 14 days of treatmentPatient-Reported Outcomes Measurement Information System perceived fatigue questionnaire (PROMIS 8a). Results given as T-score with mean of 50 and standard deviation of 10. Lower is better.

Countries

United States

Participant flow

Participants by arm

ArmCount
All Study Participants
All study participants
16
Total16

Withdrawals & dropouts

PeriodReasonFG000FG001
First Intervention (14 Days)Screen failure1516

Baseline characteristics

CharacteristicAll Study Participants
Age, Continuous71 years
STANDARD_DEVIATION 5
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
12 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
4 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
0 Participants
Race (NIH/OMB)
Black or African American
1 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants
Race (NIH/OMB)
White
14 Participants
Region of Enrollment
United States
16 Participants
Sex: Female, Male
Female
11 Participants
Sex: Female, Male
Male
5 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 470 / 160 / 16
other
Total, other adverse events
27 / 475 / 164 / 16
serious
Total, serious adverse events
0 / 470 / 160 / 16

Outcome results

Primary

Maximal Knee Extension Power

\*Maximal\* knee extension power was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 rad/s on an isokinetic dynamometer (device that controls velocity while measuring torque). \*Peak\* power at each velocity was calculated by multiplying the measured torque by that velocity, then \*maximal\* power was determined by fitting a parabolic function to these data. Higher values are better.

Time frame: 14 days

ArmMeasureValue (MEAN)Dispersion
PlaceboMaximal Knee Extension Power4.23 W/kgStandard Deviation 1.21
NitrateMaximal Knee Extension Power4.31 W/kgStandard Deviation 1.26
Primary

Maximal Knee Extension Velocity

\*Maximal\* knee extension velocity was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 rad/s on an isokinetic dynamometer (device that controls velocity while measuring torque). Peak power at each velocity was calculated by multiplying the measured torque by that velocity, then \*maximal\* knee extensor velocity was determined by fitting a parabolic function to these data (\*maximal\* knee extension velocity = 2 x fitted velocity at which \*maximal\* power is developed). Higher values are better.

Time frame: 14 days

ArmMeasureValue (MEAN)Dispersion
PlaceboMaximal Knee Extension Velocity12.2 rad/sStandard Deviation 1.8
NitrateMaximal Knee Extension Velocity12.7 rad/sStandard Deviation 1.8
Primary

Maximal Knee Extension Velocity

\*Maximal\* knee extension velocity was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 radians per second on an isokinetic dynamometer (device that controls velocity while measuring torque). Peak power at each velocity was calculated by multiplying the measured torque by that velocity, then a parabolic function was fit to these calculated data to predict \*maximal\* knee extensor velocity. Higher values are better.

Time frame: 1 day

ArmMeasureValue (MEAN)Dispersion
PlaceboMaximal Knee Extension Velocity12.2 radians per secondStandard Deviation 1.9
NitrateMaximal Knee Extension Velocity12.7 radians per secondStandard Deviation 2.1
Primary

Muscle Knee Extensor Power

This outcome was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 radians per second on an isokinetic dynamometer (device that controls velocity while measuring torque). \*Peak\* power at each velocity was calculated by multiplying the measured torque by that velocity, then a parabolic function was fit to these calculated data to predict \*maximal\* knee extensor power. Higher values are better.

Time frame: 1 day

ArmMeasureValue (MEAN)Dispersion
PlaceboMuscle Knee Extensor Power3.98 Watts per kilogram body massStandard Deviation 1.18
NitrateMuscle Knee Extensor Power4.26 Watts per kilogram body massStandard Deviation 1.37
Other Pre-specified

Perceived Fatigue

Patient-Reported Outcomes Measurement Information System perceived fatigue questionnaire (PROMIS 8a). Results given as T-score with mean of 50 and standard deviation of 10. Lower is better.

Time frame: 1 and 14 days of treatment

ArmMeasureGroupValue (MEAN)Dispersion
PlaceboPerceived Fatigue1 d42.3 T-scoreStandard Deviation 9.1
PlaceboPerceived Fatigue14 d39.3 T-scoreStandard Deviation 7.1
NitratePerceived Fatigue1 d43.2 T-scoreStandard Deviation 8.9
NitratePerceived Fatigue14 d40.8 T-scoreStandard Deviation 6.6
Other Pre-specified

Physical Function

Patient-Reported Outcomes Measurement Information System physical function questionnaire (PROMIS 20a). Results given as T-score with mean of 50 and standard deviation of 10. Higher is better.

Time frame: 1,14 days of treatment

ArmMeasureGroupValue (MEAN)Dispersion
PlaceboPhysical Function1 day53.0 T-scoreStandard Deviation 6.8
PlaceboPhysical Function14 days54.7 T-scoreStandard Deviation 6.8
NitratePhysical Function1 day52.2 T-scoreStandard Deviation 7.4
NitratePhysical Function14 days57.0 T-scoreStandard Deviation 6.3
Post Hoc

Plasma 4-hydroxynonenal

4-hydroxynonenal is an indicator of oxidative damage to lipids (fats). It was measured using a commercial enzyme-linked immunosuppressant assay kit. Lower is better.

Time frame: 1 and 14 days of treatment

ArmMeasureGroupValue (MEAN)Dispersion
PlaceboPlasma 4-hydroxynonenalPre-treatment43.9 ug/mLStandard Deviation 25
PlaceboPlasma 4-hydroxynonenalPost-treatment38.4 ug/mLStandard Deviation 26.6
NitratePlasma 4-hydroxynonenalPre-treatment38.1 ug/mLStandard Deviation 24.6
NitratePlasma 4-hydroxynonenalPost-treatment35.7 ug/mLStandard Deviation 24
Post Hoc

Plasma 8-hydroxydeoxyguanosine

Plasma 8-hydroxydeoxyguanosine is an indicator of oxidative damage to DNA/RNA. It was measured using a commercial enzyme-linked immunosuppressant assay kit. Lower is better.

Time frame: 1 and 14 days of treatment

ArmMeasureGroupValue (MEAN)Dispersion
PlaceboPlasma 8-hydroxydeoxyguanosinePre-treatment11.4 mg/mLStandard Deviation 4
PlaceboPlasma 8-hydroxydeoxyguanosinePost-treatment11.6 mg/mLStandard Deviation 3.9
NitratePlasma 8-hydroxydeoxyguanosinePre-treatment11.5 mg/mLStandard Deviation 4.5
NitratePlasma 8-hydroxydeoxyguanosinePost-treatment11.7 mg/mLStandard Deviation 4.5
Other Pre-specified

Plasma Nitrate

Plasma nitrate concentrations

Time frame: 0,1,2,3 hours after treatment at 14 days

ArmMeasureGroupValue (MEAN)Dispersion
PlaceboPlasma Nitrate0 h37 umol/LStandard Deviation 20
PlaceboPlasma Nitrate1 h35 umol/LStandard Deviation 13
PlaceboPlasma Nitrate2 h35 umol/LStandard Deviation 11
PlaceboPlasma Nitrate3 h35 umol/LStandard Deviation 14
NitratePlasma Nitrate3 h780 umol/LStandard Deviation 292
NitratePlasma Nitrate0 h190 umol/LStandard Deviation 153
NitratePlasma Nitrate2 h815 umol/LStandard Deviation 281
NitratePlasma Nitrate1 h740 umol/LStandard Deviation 241
Other Pre-specified

Plasma Nitrate

Plasma nitrate concentrations were measured using high performance liquid chromatography.

Time frame: 0,1,2,3 hours after treatment at 1 day

ArmMeasureGroupValue (MEAN)Dispersion
PlaceboPlasma Nitrate0 h35 umol/LStandard Deviation 24
PlaceboPlasma Nitrate1 h35 umol/LStandard Deviation 22
PlaceboPlasma Nitrate2 h33 umol/LStandard Deviation 20
PlaceboPlasma Nitrate3 h33 umol/LStandard Deviation 16
NitratePlasma Nitrate3 h661 umol/LStandard Deviation 247
NitratePlasma Nitrate0 h39 umol/LStandard Deviation 19
NitratePlasma Nitrate2 h698 umol/LStandard Deviation 214
NitratePlasma Nitrate1 h601 umol/LStandard Deviation 258
Other Pre-specified

Plasma Nitrite

Plasma nitrite concentrations were measured using high performance liquid chromatography.

Time frame: 0,1,2,3 hours after treatment at 14 days

ArmMeasureGroupValue (MEAN)Dispersion
PlaceboPlasma Nitrite0 h0.307 umol/LStandard Deviation 0.294
PlaceboPlasma Nitrite1 h0.308 umol/LStandard Deviation 0.247
PlaceboPlasma Nitrite2 h0.353 umol/LStandard Deviation 0.344
PlaceboPlasma Nitrite3 h0.275 umol/LStandard Deviation 0.286
NitratePlasma Nitrite3 h0.989 umol/LStandard Deviation 1.039
NitratePlasma Nitrite0 h0.615 umol/LStandard Deviation 0.671
NitratePlasma Nitrite2 h1.053 umol/LStandard Deviation 1.144
NitratePlasma Nitrite1 h0.972 umol/LStandard Deviation 1.039
Other Pre-specified

Plasma Nitrite

Plasma nitrite concentrations were measured using high performance liquid chromatography.

Time frame: 0,1,2,3 hours after treatment at 1 day

ArmMeasureGroupValue (MEAN)Dispersion
PlaceboPlasma Nitrite0 h0.364 umol/LStandard Deviation 0.283
PlaceboPlasma Nitrite1 h0.382 umol/LStandard Deviation 0.338
PlaceboPlasma Nitrite2 h0.379 umol/LStandard Deviation 0.401
PlaceboPlasma Nitrite3 h0.374 umol/LStandard Deviation 0.376
NitratePlasma Nitrite3 h1.243 umol/LStandard Deviation 1.078
NitratePlasma Nitrite0 h0.400 umol/LStandard Deviation 0.356
NitratePlasma Nitrite2 h1.104 umol/LStandard Deviation 0.847
NitratePlasma Nitrite1 h0.904 umol/LStandard Deviation 0.826
Post Hoc

Plasma Protein Carbonyls

Protein carbonyls are an indicator of oxidative damage to proteins. It was measured using a commercial enzyme-linked immunosuppressant assay kit. Lower is better.

Time frame: 1 and 14 days of treatment

ArmMeasureGroupValue (MEAN)Dispersion
PlaceboPlasma Protein CarbonylsPre-treatment3.71 nmol/mgStandard Deviation 1.4
PlaceboPlasma Protein CarbonylsPost-treatment3.79 nmol/mgStandard Deviation 1.67
NitratePlasma Protein CarbonylsPre-treatment4.00 nmol/mgStandard Deviation 1.67
NitratePlasma Protein CarbonylsPost-treatment4.46 nmol/mgStandard Deviation 2.17

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026