Dose-response Effect of Dietary Nitrate on Muscle Function in Older Individuals

February 18, 2024 updated by: Andrew Coggan, Indiana University
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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of Health and Human Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years to 79 years (Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
3.3 mL/kg concentrated beet root juice *depleted of nitrate* Other names: Beet It Sport Nitrate 400 placebo
Dietary supplement: Beet root juice
Beet root juice
Other Names:
  • Beet It Sport Nitrate 400
Active Comparator: low nitrate

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
Dietary supplement: Beet root juice
Beet root juice
Other Names:
  • Beet It Sport Nitrate 400
Active Comparator: high nitrate

3.3 mL/kg concentrated beet root juice containing nitrate

Other names:Beet It Sport Nitrate 400
Dietary supplement: Beet root juice
Beet root juice
Other Names:
  • Beet It Sport Nitrate 400

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximal Knee Extensor Velocity
Time Frame: 1 day
Maximal knee extensor velocity determined using isokinetic dynamometry
1 day
Maximal Knee Extensor Power
Time Frame: 1 day
Maximal knee extensor power determined using isokinetic dynamometry
1 day

Secondary Outcome Measures

Outcome Measure
Time Frame
Plasma Nitrite
Time Frame: 0, 1, 2, 3 h after ingestion
0, 1, 2, 3 h after ingestion
Plasma Nitrate
Time Frame: 0, 1, 2, 3 h after ingestion
0, 1, 2, 3 h after ingestion
Breath Nitric Oxide
Time Frame: 0, 1, 2, 3 h after ingestion
0, 1, 2, 3 h after ingestion

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma nitrate
Time Frame: 0, 1, 2 3 hours after treatment
Plasma nitrate concentrations
0, 1, 2 3 hours after treatment
Plasma nitrite
Time Frame: 0, 1, 2 3 hours after treatment
Plasma nitrate concentrations
0, 1, 2 3 hours after treatment
Breath nitric oxide
Time Frame: 0, 1, 2 3 hours after treatment
Breath nitric oxide level
0, 1, 2 3 hours after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indiana University

Investigators

  • Principal Investigator: Andrew R Coggan, PhD, Indiana University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2018

Primary Completion (Actual)

July 31, 2021

Study Completion (Actual)

July 31, 2021

Study Registration Dates

First Submitted

July 11, 2018

First Submitted That Met QC Criteria

July 11, 2018

First Posted (Actual)

July 23, 2018

Study Record Updates

Last Update Posted (Actual)

July 29, 2024

Last Update Submitted That Met QC Criteria

February 18, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1712606816

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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