Long COVIDPhase 2NCT05618574

Nitrite Supplementation in Long COVID Patients

A Phase 2 study testing 140 ml per day of Beet-It nitrate beverage (James White Drinks Ltd., Ipswich, UK) in people with Long COVID and Cardiorespiratory Fitness, run by VA Office of Research and Development at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Long COVID, Cardiorespiratory Fitness
What is being tested?: 140 ml per day of Beet-It nitrate beverage (James White Drinks Ltd., Ipswich, UK)
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 17 participants
Where: 1 siteUnited States
Study dates: 1 Dec 2023to 14 Feb 2025
Phase: Phase 2
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Veterans with prior COVID-19, with residual symptoms of long COVID including increased fatigability.

Who cannot join

Blood pressure <110/60 mmHg, either systolic or diastolic value which may affect participant safety during assessments will be at the discretion of the study physician
Unable to hold warfarin, novel oral anticoagulants (NOACs) or aspirin for 3 days prior to muscle biopsy, or to hold thienopyridine medications for 5 days prior to muscle biopsy
Current use of organic nitrates or phosphodiesterase type 5 (PDE5) inhibitors
Orthopedic or other chronic condition which limits physical activity or functional testing assessments
End-stage disease
Dementia or other reason unable to give informed consent

Show all 15Show fewer

Anemia (hemoglobin <11.0 g/dL in men or hemoglobin <10.0 g/dL in women)
Unstable psychiatric diagnosis
Clinically significant alcohol intake or substance abuse
Chronic use of oral corticosteroids or medications that affect muscle function
Use of anti-bacterial mouthwash or antacids that confound the nitrate/nitrite/NO pathway.
Suicidal ideations
Unwilling to hold Viagra-like drugs (i.e. Viagra, Cialis, Levitra, other phosphodiesterase inhibitors)
Involved in another greater than minimal risk study
Other clinically unstable medical condition as determined by the study physician

Trial locations and contacts

1 site in 1 country.

United States1 site

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
Pittsburgh, Pennsylvania, 15240

Other trials in United States

About this study

Official title: Nitrite Supplementation to Mitigate Fatigability and Increase Function in Long COVID Patients

Potential benefits of a nitrate-rich juice supplement to improve skeletal muscle function and associated physical capacity will be studied in patients with Long COVID. Consenting patients with Long-COVID will be randomized to receive Beet-It nitrate beverage group versus a nitrate-depleted placebo beverage. Both groups will receive physical therapy at the long COVID Clinic at VAPHS with therapeutic goals to improve strength, balance, inspiratory, and aerobic capabilities. Physical therapy will last for 2 weeks and include 2 or 3 sessions with a physical therapist a week depending on each individual's exercise tolerance. These sessions can take place on-site or at home (or a hybrid combination) All participants will undergo functional assessments and tissue assessments before and after the 14-day study intervention.

Read the detailed description

In a proof of concept pilot, the investigators will study 30 Veterans with long COVID, comparing 15 who consume two weeks of daily nitrate-rich beetroot juice versus matched Veterans who consume a nitrate-depleted placebo. Nitrate is metabolized to increase cellular nitric oxide once it is ingested. Nitric oxide (NO) is a signaling molecule that contributes to numerous physiological functions, including enhanced skeletal muscle mitochondrial respiration, which may thereby lead to decreased fatigability and increased physical function. NO is commonly produced from the conversion of the amino acid L-arginine to L-citrulline in the presence of oxygen. However, inorganic nitrate provided as a dietary supplement can serve as an additional substrate for bioactive nitrite and downstream NO, particularly during the ischemic stress of exercise. In this study, consenting patients with Long-COVID will be randomized to receive Beet-It nitrate beverage group as a source of inorganic nitrites and NO, versus a nitrate-depleted placebo beverage. Both groups will undergo simultaneous physical therapy. Primary endpoints center on meaningful clinical changes, including fatigability (i.e., rating of perceived exertion during steady-state walking), cardiorespiratory fitness (i.e., peak oxygen utilization [VO2] as well as submaximal VO2 at anaerobic threshold [VAT]). In addition, serology and skeletal muscle assessments will include nitrate and nitrite levels and mitochondrial respiration to analyze nitrite-mediated mechanisms underlying functional changes.

Principal investigator Daniel Forman, MD has developed expertise in nitrite therapeutics using nitrite capsule supplements for older sedentary adults in relation to sedentariness and heart failure. This SPiRE proposal focuses nitrite therapeutics to both younger and older adults with long COVID.

Aims: We will conduct a pilot randomized controlled trial to study the benefits of nitrate-rich beetroot juice versus placebo in 30 Veterans with a diagnosis of Long COVID. All participants will receive a daily study juice intervention for 2 weeks. All participants will be encouraged to participate in the standard physical therapy program in the Long COVID clinic.

Aim 1: To study the efficacy of nitrate-rich juice supplementation to reduce fatigability as measured by rating of perceived exertion (RPE) during submaximal steady-state 1.5 mile per hour walking after two weeks of treatment in patients with Long COVID. Walking efficiency (VO2 per kg) will also be assessed in association with fatigability.

Aim 2: To study the benefits of nitrate-rich juice supplementation to increase cardiorespiratory fitness (peak oxygen utilization [VO2], VO2 at anaerobic threshold (VAT), 400-meter corridor walk (400MCW), short physical performance battery (SPPB) in patients with Long COVID after two weeks of treatment.

Aim 3: To explore the utility of nitrate-rich juice supplementation to enhance skeletal muscle mitochondrial respiration in patients with Long COVID as measured by ex vivo Oroboros analysis.

Conditions: Long COVID, Cardiorespiratory Fitness
Being tested: 140 ml per day of Beet-It nitrate beverage (James White Drinks Ltd., Ipswich, UK), 210 ml of nitrate-depleted placebo
Keywords: Nitrate therapeutics, Long COVID, Skeletal Muscle Mitochondrial Respiration, Fatigability, Cardiorespiratory Fitness
Medical subject headings: Post-Acute COVID-19 Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

140 ml per day of Beet-It nitrate beverage (James White Drinks Ltd., Ipswich, UK)Dietary supplement
The investigators propose to study the benefits nitrite therapeutics, using nitrate-rich beetroot juice to increase serum nitrite. The investigators hypothesize that increased nitrite will improve functional metrics and reduce fatigability in Veterans with long COVID as a result of enhanced skeletal muscle mitochondrial respiration. Participant will receive 140 ml per day of Beet-It nitrate beverage for 16 mmol of nitrate/day for 14 days vs the placebo.
210 ml of nitrate-depleted placeboDietary supplement
Participants randomized to the placebo arm will receive 210 ml of nitrate-depleted beverage (cranberry juice) per day for 14 days.

Study groups in NCT05618574
Study group	Role	What they receive
Beet-It nitrate beverage	Active comparator	Participant will receive 140 ml per day of Beet-It nitrate beverage for for 14 days. All participants will be encouraged to undergo physical therapy 2-3 times per week based on tolerance for activity and recovery needed after each session. Physical therapy will be standardized to include strength, balance, inspiratory muscle training, and aerobic training. Participants randomized to this arm will be assessed at baseline and follow-up visits on all outcome measures. Receives: Dietary Supplement: 140 ml per day of Beet-It nitrate beverage (James White Drinks Ltd., Ipswich, UK)
Nitrate-depleted placebo	Placebo comparator	Participants will receive 210 ml of nitrate-depleted placebo for 14 days. All participants will be encouraged to undergo physical therapy 2-3 times per week based on tolerance for activity and recovery needed after each session. Physical therapy will be standardized to include strength, balance, inspiratory muscle training, and aerobic training. Participants randomized to this arm will be assessed at baseline and follow-up visits on all outcome measures. Receives: Dietary Supplement: 210 ml of nitrate-depleted placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Fatigability
Rating of Rate of Perceived Exertion (RPE) during the 5th minute of a 5-min of a 1.5 mile per hour steady-state treadmill walking test is used as an assessment of fatigability. RPE scale is from 6 (no physical exertion) - 20 (maximal exertion/very hard). This is assessed before and after approx. 14 days of supplementation with Beet-It nitrate beverage vs. placebo. The mean change from baseline to follow-up is used as the outcome measure.
Measured: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Walking Efficiency
Walking efficiency (VO2/kg) is assessed by incorporating VO2 assessments during the 5-min steady-state walking protocol. This is assessed using cardiopulmonary exercise testing (CPET) equipment. A lower VO2 for the same functional workload indicates improved efficiency. This is assessed before and after approx. 14 days of supplementation with Beet-It nitrate beverage vs. placebo. The mean change from baseline to follow-up is used as the outcome measure.
Measured: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks

Secondary outcomes (10)

400m Corridor Walk Test (400MCW)
This test measures the amount of time it takes the participant to walk a 400-meter course to assess cardiovascular and pulmonary fitness or to predict adverse outcomes such as mobility disability. his is assessed before and after approx. 14 days of supplementation with Beet-It nitrate beverage vs. placebo. The mean change from baseline to follow-up is used as the outcome measure.
Measured: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Short Performance Physical Battery (SPPB)
The SPPB is a test of balance, gait, strength, and endurance that combines gait speed, chair stand and balance tests. SPPB scaled score ranges from 0 - 12. Scores of 0 indicate that the participant is unable/barely able to perform the tasks, while 12 indicates they completed all tasks optimally. This is assessed before and after approx. 14 days of supplementation with Beet-It nitrate beverage vs. placebo. The mean change from baseline to follow-up is used as the outcome measure.
Measured: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Peak Oxygen Utilization (VO2) Non-normalized
Peak VO2 (ml/min) non-normalized to weight will be collected using symptom-limited cardiopulmonary exercise testing (CPET). This is assessed before and after approx. 14 days of supplementation with Beet-It nitrate beverage vs. placebo. The mean change from baseline to follow-up is used as the outcome measure.
Measured: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Peak Oxygen Utilization (VO2) Normalized to Weight
Peak VO2 will be collected using symptom-limited cardiopulmonary exercise testing (CPET). The average sedentary male will achieve a peak VO2 of approximately 35 to 40 mL/kg/min. The average sedentary female will score a VO2 max of between 27 and 30 mL/kg/min. This is assessed before and after approx. 14 days of supplementation with Beet-It nitrate beverage vs. placebo. The mean change from baseline to follow-up is used as the outcome measure.
Measured: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
VO2 at Anaerobic Threshold (AT) Non-normalized
VO2 (ml/min) non-normalized at AT will be assessed using symptom-limited CPET. The VO2 at AT for the general population occurs at approximately 50-60% of the peak VO2. This is assessed before and after approx. 14 days of supplementation with Beet-It nitrate beverage vs. placebo. The mean change from baseline to follow-up is used as the outcome measure.
Measured: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
VO2 at Anaerobic Threshold (AT) Normalized to Weight
VO2 (ml/kg/min) at AT will be assessed using symptom-limited CPET. The VO2 at AT for the general population occurs at approximately 50-60% of the peak VO2. This is assessed before and after approx. 14 days of supplementation with Beet-It nitrate beverage vs. placebo. The mean change from baseline to follow-up is used as the outcome measure.
Measured: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Mitochondrial Respiration
To determine the impact of nitrite-rich juice supplementation on skeletal muscle mitochondrial respiration on patients with Long COVID, muscle biopsy of the vastus lateralis will be completed at baseline and following 2 weeks of supplementation. At each time point muscle respiratory capacity will be measured using the Oroboros-2k system. The main outcome will be change in state 3 respiration (maxOXPHOS, pmol/mg/min wet.wt.). Data will be reported as Mean +/- standard deviation.
Measured: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Serum Nitrate
5 ml of blood will be collected from participants and spun down using a centrifuge to separate the plasma from the rest of the blood. Serological sampling is completed at baseline and at final visit. Serum nitrite (µmol/L) and nitrate levels (µmol/L) will be measured at baseline and after the study intervention to evaluate the successful metabolism of nitrate (in beetroot juice) to nitrite.
Measured: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Serum Nitrite
5 ml of blood will be collected from participants and spun down using a centrifuge to separate the plasma from the rest of the blood. Serological sampling is completed at baseline and at final visit. Serum nitrite (µmol/L) and nitrate levels (µmol/L) will be measured at baseline and after the study intervention to evaluate the successful metabolism of nitrate (in beetroot juice) to nitrite.
Measured: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Veterans RAND-12 (VR-12)
The Veterans RAND-12 (VR-12) is a brief self-administered health survey comprised of 12 items used to measure health related quality of life, estimate disease burden, and evaluate disease-specific benchmarks using two score components: Physical Component Score (PCS) and Mental Component Score (MCS). Summary scores are standardized using a t-score transformation (normalized to US population with mean of 50 and standard deviation of 10). A higher PCS represents better self-reported overall physical function; a higher MCS represents better emotional well-being and fewer mental health limitations.
Measured: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Dec 202314 Feb 2025

First posted16 Nov 2022
Study start1 Dec 2023
Primary completion12 Feb 2025
Study completion14 Feb 2025

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 (20)Papers the sponsor has linked to this study.
Other trials for Long COVIDStudies of the same condition, open and under way.
More trials run by VA Office of Research and DevelopmentThe 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: In a randomized controlled, blinded design, participants will receive 140 ml per day of Beet-It nitrate beverage (James White Drinks Ltd., Ipswich, UK) for 14 days versus a 210 ml of nitrate-depleted placebo. All participants are encouraged to participate in the standard physical therapy program in the Long COVID clinic 2-3 times per week based on tolerance for activity and recovery needed after each session.
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05618574
Sponsor's protocol ID: F4409-P
Other IDs: 1I21RX004409
Status last verified: Aug 2026
First submitted: 14 Nov 2022
Last updated: 26 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Leuenberger AE. [Clinical experience with the O'Malley LOG2 photocoagulator (author's transl)]. Klin Monbl Augenheilkd. 1977 Jan;170(1):143-6. German.
PubMed 850349
Gullis RJ, Rowe CE. Pharmacological studies on the stimulation of the phospholipase A2-acylation system of synaptic membranes of brain, by neurotransmitters and other agonists. J Neurochem. 1976 Jun;26(6):1217-30. doi: 10.1111/j.1471-4159.1976.tb07010.x. No abstract available.
PubMed 778343
Appelboom T, Famaey JP. [Allopurinol and gouty hyperuricemia : apropos of 30 cases treated by a single daily dose]. Brux Med. 1977 Mar;57(3):133-7. No abstract available. French.
PubMed 861817
Westman WE. Problems in implementing U.S. water quality goals. Am Sci. 1977 Mar-Apr;65(2):197-203. No abstract available.
PubMed 403838
Ansehn S, Winblad B. Surface morphology of Candida albicans after treatment with antimycotic drugs. Mykosen Suppl. 1978;1:322-7. No abstract available.
PubMed 400881
Baggiolini M. [The release of proteinases from neutrophil leukocytes and macrophages]. Bull Schweiz Akad Med Wiss. 1979 Sep;35(4-6):283-99. German.
PubMed 394786
Devine CJ Jr, Franz JP, Horton CE. Evaluation and treatment of patients with failed hypospadias repair. Trans Am Assoc Genitourin Surg. 1977;69:4-7.
PubMed 369094
ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available.
PubMed 12091180
Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, Scherr PA, Wallace RB. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol. 1994 Mar;49(2):M85-94. doi: 10.1093/geronj/49.2.m85.
PubMed 8126356
Pesta D, Gnaiger E. High-resolution respirometry: OXPHOS protocols for human cells and permeabilized fibers from small biopsies of human muscle. Methods Mol Biol. 2012;810:25-58. doi: 10.1007/978-1-61779-382-0_3.
PubMed 22057559
Vogiatzis I, Zakynthinos S. The physiological basis of rehabilitation in chronic heart and lung disease. J Appl Physiol (1985). 2013 Jul 1;115(1):16-21. doi: 10.1152/japplphysiol.00195.2013. Epub 2013 Apr 25.
PubMed 23620491
Czyzewski K, Pudelski J, Dzielicki J, Guzy R. [Respiratory disorders as a consequence of thoracic injuries]. Pol Przegl Chir. 1979 Jan;51(1):1-6. No abstract available. Polish.
PubMed 461237
Ferguson SK, Woessner MN, Holmes MJ, Belbis MD, Carlstrom M, Weitzberg E, Allen JD, Hirai DM. Effects of inorganic nitrate supplementation on cardiovascular function and exercise tolerance in heart failure. J Appl Physiol (1985). 2021 Apr 1;130(4):914-922. doi: 10.1152/japplphysiol.00780.2020. Epub 2021 Jan 21.
PubMed 33475460
Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxf). 2007 Sep;191(1):59-66. doi: 10.1111/j.1748-1716.2007.01713.x. Epub 2007 Jul 17.
PubMed 17635415
Eggebeen J, Kim-Shapiro DB, Haykowsky M, Morgan TM, Basu S, Brubaker P, Rejeski J, Kitzman DW. One Week of Daily Dosing With Beetroot Juice Improves Submaximal Endurance and Blood Pressure in Older Patients With Heart Failure and Preserved Ejection Fraction. JACC Heart Fail. 2016 Jun;4(6):428-37. doi: 10.1016/j.jchf.2015.12.013. Epub 2016 Feb 10.
PubMed 26874390

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Nitrite Supplementation to Mitigate Fatigability and Increase Function in Long COVID Patients
ClinicalTrials.gov ID: NCT05618574
Acronym / sponsor ID: F4409-P
Conditions: Long COVID, Cardiorespiratory Fitness
Keywords: Nitrate therapeutics, Long COVID, Skeletal Muscle Mitochondrial Respiration, Fatigability, Cardiorespiratory Fitness
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: VA Office of Research and DevelopmentUS federal agency
Study start: 1 Dec 2023 (actual)
Primary completion: 12 Feb 2025 (actual)
Study completion: 14 Feb 2025 (actual)
First posted: 16 Nov 2022 (actual)
Results: Posted 26 Aug 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Aim 3: To explore the utility of nitrate-rich juice supplementation to enhance skeletal muscle mitochondrial respiration in patients with Long COVID as measured by ex vivo Oroboros analysis.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2
Model description: In a randomized controlled, blinded design, participants will receive 140 ml per day of Beet-It nitrate beverage (James White Drinks Ltd., Ipswich, UK) for 14 days versus a 210 ml of nitrate-depleted placebo. All participants are encouraged to participate in the standard physical therapy program in the Long COVID clinic 2-3 times per week based on tolerance for activity and recovery needed after each session.

Arm	Type	Receives
Beet-It nitrate beverage	Active comparator	Dietary Supplement: 140 ml per day of Beet-It nitrate beverage (James White Drinks Ltd., Ipswich, UK)Participant will receive 140 ml per day of Beet-It nitrate beverage for for 14 days. All participants will be encouraged to undergo physical therapy 2-3 times per week based on tolerance for activity and recovery needed after each session. Physical therapy will be standardized to include strength, balance, inspiratory muscle training, and aerobic training. Participants randomized to this arm will be assessed at baseline and follow-up visits on all outcome measures.
Nitrate-depleted placebo	Placebo comparator	Dietary Supplement: 210 ml of nitrate-depleted placeboParticipants will receive 210 ml of nitrate-depleted placebo for 14 days. All participants will be encouraged to undergo physical therapy 2-3 times per week based on tolerance for activity and recovery needed after each session. Physical therapy will be standardized to include strength, balance, inspiratory muscle training, and aerobic training. Participants randomized to this arm will be assessed at baseline and follow-up visits on all outcome measures.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Veterans with prior COVID-19, with residual symptoms of long COVID including increased fatigability.

Key exclusion criteria (15 listed)

Blood pressure <110/60 mmHg, either systolic or diastolic value which may affect participant safety during assessments will be at the discretion of the study physician
Unable to hold warfarin, novel oral anticoagulants (NOACs) or aspirin for 3 days prior to muscle biopsy, or to hold thienopyridine medications for 5 days prior to muscle biopsy
Current use of organic nitrates or phosphodiesterase type 5 (PDE5) inhibitors
Orthopedic or other chronic condition which limits physical activity or functional testing assessments
End-stage 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
140 ml per day of Beet-It nitrate beverage (James White Drinks Ltd., Ipswich, UK)The investigators propose to study the benefits nitrite therapeutics, using nitrate-rich beetroot juice to increase serum nitrite. The investigators hypothesize that increased nitrite will improve functional metrics and reduce fatigability in Veterans with long COVID as a result of enhanced skeletal muscle mitochondrial respiration. Participant will receive 140 ml per day of Beet-It nitrate beverage for 16 mmol of nitrate/day for 14 days vs the placebo.	Dietary supplement	Beet-It nitrate beverage
210 ml of nitrate-depleted placeboParticipants randomized to the placebo arm will receive 210 ml of nitrate-depleted beverage (cranberry juice) per day for 14 days.	Dietary supplement	Nitrate-depleted placebo

Primary outcome

Fatigability
Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Rating of Rate of Perceived Exertion (RPE) during the 5th minute of a 5-min of a 1.5 mile per hour steady-state treadmill walking test is used as an assessment of fatigability. RPE scale is from 6 (no physical exertion) - 20 (maximal exertion/very hard). This is assessed before and after approx. 14 days of supplementation with Beet-It nitrate beverage vs. placebo. The mean change from baseline to follow-up is used as the outcome measure.
Walking Efficiency
Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Walking efficiency (VO2/kg) is assessed by incorporating VO2 assessments during the 5-min steady-state walking protocol. This is assessed using cardiopulmonary exercise testing (CPET) equipment. A lower VO2 for the same functional workload indicates improved efficiency. This is assessed before and after approx. 14 days of supplementation with Beet-It nitrate beverage vs. placebo. The mean change from baseline to follow-up is used as the outcome measure.

10 secondary outcomes

400m Corridor Walk Test (400MCW)
Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Short Performance Physical Battery (SPPB)
Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Peak Oxygen Utilization (VO2) Non-normalized
Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Peak Oxygen Utilization (VO2) Normalized to Weight
Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
VO2 at Anaerobic Threshold (AT) Non-normalized
Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
VO2 at Anaerobic Threshold (AT) Normalized to Weight
Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Mitochondrial Respiration
Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Serum Nitrate
Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Serum Nitrite
Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks
Veterans RAND-12 (VR-12)
Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks

Results and safety

Results posted to the registry on 26 Aug 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Beet-It Nitrate Beverage	8	6
Nitrate-depleted Placebo	9	9

Primary outcome: Fatigability

Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks. Mean (Standard Deviation). Unit: Score on a scale

Measure	Beet-It Nitrate Beverage n = 5	Nitrate-depleted Placebo n = 9
Value	0.2 (1.5)	-0.7 (0.9)

Beet-It Nitrate Beverage vs Nitrate-depleted Placebo: Mean Difference (Net): 0.0, p = 0.9461, ANCOVA

Population analysed: 3 participants did not have follow-up CPET data for fatigability due to safety concerns/no baseline assessment (n=1), participant withdrawal (n=1), unable to reach/loss to follow-up (n=1).

Primary outcome: Walking Efficiency

Time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks. Mean (Standard Deviation). Unit: ml/kg/min

Measure	Beet-It Nitrate Beverage n = 5	Nitrate-depleted Placebo n = 8
Value	-0.7 (1.4)	-0.8 (0.9)

Beet-It Nitrate Beverage vs Nitrate-depleted Placebo: Mean Difference (Net): 0.5, p = 0.4566, ANCOVA

Population analysed: 4 participants did not have follow-up CPET data for walking efficiency due to safety concerns/no baseline assessment (n=1), participant withdrawal (n=1), unable to reach/loss to follow-up (n=1), missing data (n=1).

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: From enrollment until the end of follow-up, approximately 14 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Beet-It Nitrate Beverage	0 of 8 (0%)	5 of 8 (62.5%)	0 of 8
Nitrate-depleted Placebo	0 of 9 (0%)	0 of 9 (0%)	0 of 9

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 850349Leuenberger AE. [Clinical experience with the O'Malley LOG2 photocoagulator (author's transl)]. Klin Monbl Augenheilkd. 1977 Jan;170(1):143-6. German.
Background: PubMed 778343Gullis RJ, Rowe CE. Pharmacological studies on the stimulation of the phospholipase A2-acylation system of synaptic membranes of brain, by neurotransmitters and other agonists. J Neurochem. 1976 Jun;26(6):1217-30. doi: 10.1111/j.1471-4159.1976.tb07010.x. No abstract available.
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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.

Daniel E Forman, MD principal investigator

VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 15 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 26 Aug 2026. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 26 Aug 2026). 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?

Fatigability (time frame: Baseline (pre-intervention) to Follow-up (post-intervention); approx. 2 weeks). 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 NCT05618574, which also lists 20 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 26 Aug 2026.