PhysiologyNO-SUPNCT02850367
Effect of NO Precursors on Physiological Responses to Exercise
A study testing Nitrate, Nitrate and L-Arginine and Nitrate and L-Citrulline in people with Physiology, run by University Hospital, Grenoble at 1 site in France.
Trial summary
NO is an ubiquitous molecule contributing to many physiological functions such as vasodilation, immune and oxidative stress responses. NO production can be supplemented either by providing substrate to the NO-synthase (L-Arginine and L-Citruline) or by providing nitrate which can lead to NO. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Physiology
- What is being tested?
- Nitrate, Nitrate and L-Arginine and Nitrate and L-Citrulline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 1 siteFrance
- Study dates
- 9 May 2016to Sep 2021
- Phase
- Interventional
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Sedentary subjects
- No cardiovascular, respiratory, metabolic and neurological disorders
Who cannot join
- Body mass index > 28 kg.m-2
- Smoker
- Alcool intake > 10g/day
- Psychiatric diseases
- Subjects under treatment able to interfere with their cardiovascular, metabolic and neurological status
Trial locations and contacts
1 site in 1 country.
France1 site
Grenoble University Hospital
Grenoble, Auvergne-Rhône-Alpes, 38043
About this study
Official title: The Effect of NO Precursors on Physiological Responses to Exercise
NO is an ubiquitous molecule contributing to many physiological functions such as vasodilation, immune and oxidative stress responses. NO production can be supplemented either by providing substrate to the NO-synthase (L-Arginine and L-Citruline) or by providing nitrate which can lead to NO. In the present project the investigators evaluate the effect of various acute and chronic oral NO precursors supplementation on exercise performance and responses in healthy young and older subjects.
- Conditions
- Physiology
- Being tested
- Nitrate, Nitrate and L-Arginine, Nitrate and L-Citrulline, Placebo, Evaluation of post-ischemic vascular reactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NitrateDietary supplement
Subjects will be supplemented orally either acutely or chronically (4-8 weeks) with NO precursors.
Nitrate and L-ArginineDietary supplement
Subjects will be supplemented orally either acutely or chronically (4-8 weeks) with NO precursors.
Nitrate and L-CitrullineDietary supplement
Subjects will be supplemented orally either acutely or chronically (4-8 weeks) with NO precursors.
PlaceboDietary supplement
Subjects will be supplemented orally either acutely or chronically (4-8 weeks) with a placebo.
Evaluation of post-ischemic vascular reactivityBiological
After the intake of the supplement. Concentration of hemoglobin (g/mL) in the quadriceps with the device : NIRS system Oxymon, ARTINIS.
Neuromuscular evaluationsBiological
After the intake of the supplement. Measure the stretching force in the ankle (N)
| Study group | Role | What they receive |
|---|---|---|
| Acute intake | Active comparator | Evaluation after acute intake of the food supplement. Receives: Dietary Supplement: Nitrate; Dietary Supplement: Nitrate and L-Arginine; Dietary Supplement: Nitrate and L-Citrulline; Dietary Supplement: Placebo; Biological: Evaluation of post-ischemic vascular reactivity; Biological: Neuromuscular evaluations |
| Chronic intake | Active comparator | Evaluation before and after chronic intake of the food supplement. Receives: Dietary Supplement: Nitrate and L-Citrulline; Dietary Supplement: Placebo; Biological: Evaluation of post-ischemic vascular reactivity; Biological: Neuromuscular evaluations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neuromuscular evaluations
After the intake of the supplement. Measure the stretching force in the ankle (N)
Measured: 3 half days
Evaluation of post-ischemic vascular reactivity
After the intake of the supplement. Concentration of hemoglobin (g/mL) in the quadriceps with the device : NIRS system Oxymon, ARTINIS.
Measured: 3 half days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2016 (estimated)
- Study start9 May 2016
- Primary completionSep 2021
- Study completionSep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for PhysiologyStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stéphane Doutreleau, PhD, Principal investigator, University Hospital, Grenoble
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02850367
- Sponsor's protocol ID
- 38RC14.430
- Acronym
- NO-SUP
- Status last verified
- Dec 2025
- First submitted
- 18 May 2016
- Last updated
- 29 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Jones AM. Dietary nitrate supplementation and exercise performance. Sports Med. 2014 May;44 Suppl 1(Suppl 1):S35-45. doi: 10.1007/s40279-014-0149-y.
PubMed 24791915Kapil V, Weitzberg E, Lundberg JO, Ahluwalia A. Clinical evidence demonstrating the utility of inorganic nitrate in cardiovascular health. Nitric Oxide. 2014 Apr 30;38:45-57. doi: 10.1016/j.niox.2014.03.162. Epub 2014 Mar 18.
PubMed 24650698Kelly J, Vanhatalo A, Wilkerson DP, Wylie LJ, Jones AM. Effects of nitrate on the power-duration relationship for severe-intensity exercise. Med Sci Sports Exerc. 2013 Sep;45(9):1798-806. doi: 10.1249/MSS.0b013e31828e885c.
PubMed 23475164Lasker GF, Matt CJ, Badejo AM Jr, Casey DB, Dhaliwal JS, Murthy SN, Kadowitz PJ. Intracavernosal administration of sodium nitrite as an erectile pharmacotherapy. Can J Physiol Pharmacol. 2010 Jul;88(7):770-6. doi: 10.1139/y10-032.
PubMed 20651825Lee M, Gandevia SC, Carroll TJ. Cortical voluntary activation can be reliably measured in human wrist extensors using transcranial magnetic stimulation. Clin Neurophysiol. 2008 May;119(5):1130-8. doi: 10.1016/j.clinph.2007.12.018. Epub 2008 Mar 4.
PubMed 18308630Liu TH, Wu CL, Chiang CW, Lo YW, Tseng HF, Chang CK. No effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletes. J Nutr Biochem. 2009 Jun;20(6):462-8. doi: 10.1016/j.jnutbio.2008.05.005. Epub 2008 Aug 15.
PubMed 18708287Martin MJ, Jimenez MD, Motilva V. New issues about nitric oxide and its effects on the gastrointestinal tract. Curr Pharm Des. 2001 Jul;7(10):881-908. doi: 10.2174/1381612013397645.
PubMed 11472246Moinard C, Nicolis I, Neveux N, Darquy S, Benazeth S, Cynober L. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008 Apr;99(4):855-62. doi: 10.1017/S0007114507841110. Epub 2007 Oct 22.
PubMed 17953788Moncada S. The L-arginine: nitric oxide pathway, cellular transduction and immunological roles. Adv Second Messenger Phosphoprotein Res. 1993;28:97-9. No abstract available.
PubMed 8398422Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993 Dec 30;329(27):2002-12. doi: 10.1056/NEJM199312303292706. No abstract available.
PubMed 7504210Morris CR, Morris SM Jr, Hagar W, Van Warmerdam J, Claster S, Kepka-Lenhart D, Machado L, Kuypers FA, Vichinsky EP. Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med. 2003 Jul 1;168(1):63-9. doi: 10.1164/rccm.200208-967OC. Epub 2003 Mar 5.
PubMed 12626350Ochiai M, Hayashi T, Morita M, Ina K, Maeda M, Watanabe F, Morishita K. Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men. Int J Cardiol. 2012 Mar 8;155(2):257-61. doi: 10.1016/j.ijcard.2010.10.004. Epub 2010 Nov 9.
PubMed 21067832Park JW, Piknova B, Kurtz J, Seetharaman S, Wagner SJ, Schechter AN. Effect of storage on levels of nitric oxide metabolites in platelet preparations. Transfusion. 2013 Mar;53(3):637-44. doi: 10.1111/j.1537-2995.2012.03777.x. Epub 2012 Jul 15.
PubMed 22804724Pavy B, Iliou MC, Meurin P, Tabet JY, Corone S; Functional Evaluation and Cardiac Rehabilitation Working Group of the French Society of Cardiology. Safety of exercise training for cardiac patients: results of the French registry of complications during cardiac rehabilitation. Arch Intern Med. 2006 Nov 27;166(21):2329-34. doi: 10.1001/archinte.166.21.2329.
PubMed 17130385Peacock O, Tjonna AE, James P, Wisloff U, Welde B, Bohlke N, Smith A, Stokes K, Cook C, Sandbakk O. Dietary nitrate does not enhance running performance in elite cross-country skiers. Med Sci Sports Exerc. 2012 Nov;44(11):2213-9. doi: 10.1249/MSS.0b013e3182640f48.
PubMed 22874535
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of NO Precursors on Physiological Responses to Exercise
- ClinicalTrials.gov ID
- NCT02850367
- Acronym / sponsor ID
- NO-SUP / 38RC14.430
- Conditions
- Physiology
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- 9 May 2016 (actual)
- Primary completion
- Sep 2021 (actual)
- Study completion
- Sep 2021 (actual)
- First posted
- 1 Aug 2016 (estimated)
- 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.
NO is an ubiquitous molecule contributing to many physiological functions such as vasodilation, immune and oxidative stress responses. NO production can be supplemented either by providing substrate to the NO-synthase (L-Arginine and L-Citruline) or by providing nitrate which can lead to NO. In the present project the investigators evaluate the effect of various acute and chronic oral NO precursors supplementation on exercise performance and responses in healthy young and older subjects.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acute intake | Active comparator | Dietary Supplement: Nitrate, Dietary Supplement: Nitrate and L-Arginine, Dietary Supplement: Nitrate and L-Citrulline, Dietary Supplement: Placebo, Biological: Evaluation of post-ischemic vascular reactivity, Biological: Neuromuscular evaluationsEvaluation after acute intake of the food supplement. |
| Chronic intake | Active comparator | Dietary Supplement: Nitrate and L-Citrulline, Dietary Supplement: Placebo, Biological: Evaluation of post-ischemic vascular reactivity, Biological: Neuromuscular evaluationsEvaluation before and after chronic intake of the food supplement. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Sedentary subjects
- No cardiovascular, respiratory, metabolic and neurological disorders
Key exclusion criteria (5 listed)
- Body mass index > 28 kg.m-2
- Smoker
- Alcool intake > 10g/day
- Psychiatric diseases
- Subjects under treatment able to interfere with their cardiovascular, metabolic and neurological status
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 |
|---|---|---|
| NitrateSubjects will be supplemented orally either acutely or chronically (4-8 weeks) with NO precursors. | Dietary supplement | Acute intake |
| Nitrate and L-ArginineSubjects will be supplemented orally either acutely or chronically (4-8 weeks) with NO precursors. | Dietary supplement | Acute intake |
| Nitrate and L-CitrullineSubjects will be supplemented orally either acutely or chronically (4-8 weeks) with NO precursors. | Dietary supplement | Acute intake, Chronic intake |
| PlaceboSubjects will be supplemented orally either acutely or chronically (4-8 weeks) with a placebo. | Dietary supplement | Acute intake, Chronic intake |
| Evaluation of post-ischemic vascular reactivityAfter the intake of the supplement. Concentration of hemoglobin (g/mL) in the quadriceps with the device : NIRS system Oxymon, ARTINIS. | Biological | Acute intake, Chronic intake |
| Neuromuscular evaluationsAfter the intake of the supplement. Measure the stretching force in the ankle (N) | Biological | Acute intake, Chronic intake |
Primary outcome
Neuromuscular evaluations
Time frame: 3 half days
After the intake of the supplement. Measure the stretching force in the ankle (N)
Evaluation of post-ischemic vascular reactivity
Time frame: 3 half days
After the intake of the supplement. Concentration of hemoglobin (g/mL) in the quadriceps with the device : NIRS system Oxymon, ARTINIS.
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 29 Dec 2025.
- Background: PubMed 24791915Jones AM. Dietary nitrate supplementation and exercise performance. Sports Med. 2014 May;44 Suppl 1(Suppl 1):S35-45. doi: 10.1007/s40279-014-0149-y.
- Background: PubMed 24650698Kapil V, Weitzberg E, Lundberg JO, Ahluwalia A. Clinical evidence demonstrating the utility of inorganic nitrate in cardiovascular health. Nitric Oxide. 2014 Apr 30;38:45-57. doi: 10.1016/j.niox.2014.03.162. Epub 2014 Mar 18.
- Background: PubMed 23475164Kelly J, Vanhatalo A, Wilkerson DP, Wylie LJ, Jones AM. Effects of nitrate on the power-duration relationship for severe-intensity exercise. Med Sci Sports Exerc. 2013 Sep;45(9):1798-806. doi: 10.1249/MSS.0b013e31828e885c.
- Background: PubMed 20651825Lasker GF, Matt CJ, Badejo AM Jr, Casey DB, Dhaliwal JS, Murthy SN, Kadowitz PJ. Intracavernosal administration of sodium nitrite as an erectile pharmacotherapy. Can J Physiol Pharmacol. 2010 Jul;88(7):770-6. doi: 10.1139/y10-032.
- Background: PubMed 18308630Lee M, Gandevia SC, Carroll TJ. Cortical voluntary activation can be reliably measured in human wrist extensors using transcranial magnetic stimulation. Clin Neurophysiol. 2008 May;119(5):1130-8. doi: 10.1016/j.clinph.2007.12.018. Epub 2008 Mar 4.
- Background: PubMed 18708287Liu TH, Wu CL, Chiang CW, Lo YW, Tseng HF, Chang CK. No effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletes. J Nutr Biochem. 2009 Jun;20(6):462-8. doi: 10.1016/j.jnutbio.2008.05.005. Epub 2008 Aug 15.
- Background: PubMed 11472246Martin MJ, Jimenez MD, Motilva V. New issues about nitric oxide and its effects on the gastrointestinal tract. Curr Pharm Des. 2001 Jul;7(10):881-908. doi: 10.2174/1381612013397645.
- Background: PubMed 17953788Moinard C, Nicolis I, Neveux N, Darquy S, Benazeth S, Cynober L. Dose-ranging effects of citrulline administration on plasma amino acids and hormonal patterns in healthy subjects: the Citrudose pharmacokinetic study. Br J Nutr. 2008 Apr;99(4):855-62. doi: 10.1017/S0007114507841110. Epub 2007 Oct 22.
- Background: PubMed 8398422Moncada S. The L-arginine: nitric oxide pathway, cellular transduction and immunological roles. Adv Second Messenger Phosphoprotein Res. 1993;28:97-9. No abstract available.
- Background: PubMed 7504210Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993 Dec 30;329(27):2002-12. doi: 10.1056/NEJM199312303292706. No abstract available.
- Background: PubMed 12626350Morris CR, Morris SM Jr, Hagar W, Van Warmerdam J, Claster S, Kepka-Lenhart D, Machado L, Kuypers FA, Vichinsky EP. Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med. 2003 Jul 1;168(1):63-9. doi: 10.1164/rccm.200208-967OC. Epub 2003 Mar 5.
- Background: PubMed 21067832Ochiai M, Hayashi T, Morita M, Ina K, Maeda M, Watanabe F, Morishita K. Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men. Int J Cardiol. 2012 Mar 8;155(2):257-61. doi: 10.1016/j.ijcard.2010.10.004. Epub 2010 Nov 9.
- 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.
Stéphane Doutreleau, PhD principal investigator
University Hospital, Grenoble
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nitrate, Nitrate and L-Arginine and Nitrate and L-Citrulline in people with Physiology, run by University Hospital, Grenoble at 1 site in France.
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 2 inclusion and 5 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 Dec 2025. 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 France. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Neuromuscular evaluations (time frame: 3 half days). 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 NCT02850367, which also lists 37 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 Dec 2025.