Raynaud PhenomenonNivOSeNCT03749577
Nutritional Strategies to Increase Nitric Oxide Signaling in Raynaud's Phenomenon
A study testing L-citrulline, Beetroot juice and Denitrated beetroot juice in people with Raynaud Phenomenon, run by University Hospital, Grenoble at 1 site in France.
Trial summary
The investigators aim at comparing the efficacy of a 2 weeks supplementation by L-citrulline or beetroot juice to L-citrulline placebo or denitrated beetroot juice respectively on Raynaud's phenomenon severity. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Raynaud Phenomenon
- What is being tested?
- L-citrulline, Beetroot juice and Denitrated beetroot juice
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 1 Oct 2020to 30 Jun 2022
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- BMI > 18
- Active Raynaud's Phenomenon characterized by a clinical history of Raynaud's
- Primary RP or secondary to limited (LSSc), limited or diffuse cutaneous scleroderma (lcSSc or dcSSc) according to the criteria of Leroy and Medsger.
- At least 1 RP attacks per week and a specific finger patient picture in RP attack (assessed over the 2 weeks preceding inclusion)
- Stable disease over the previous two months (i.e. recent diagnosis of SSc will be excluded)
- Patients insured by a social security scheme or beneficiaries of such a scheme
- Patients who have dated and signed the informed consent form
Who cannot join
- Uncontrolled hypertension, uncontrolled diabetes mellitus, uncontrolled angina
- Haemodynamic instability
- Pregnancy (or considering pregnancy in next 4 months) or breast feeding
- Subject in an exclusion period from another study,
- Subject under administrative or judicial supervision
- Subject not able to be contacted in case of emergency
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Grenoble University Hospital
Grenoble, 38000
Charles Khouri, PharmD, PhD, ckhouri@chu-grenoble.fr
About this study
The investigators aim at comparing the efficacy of a 2 weeks supplementation by L-citrulline or beetroot juice to L-citrulline placebo or denitrated beetroot juice respectively on Raynaud's phenomenon severity. Raynaud's phenomenon severity will be assessed through the Raynaud Condition Score, daily frequency of attacks or cumulative attack duration (expressed as min) daily collected by patients in a diary. Each Volunteer will choose his own main outcome among these 3 criteria.
Read the detailed description
Raynaud's phenomenon (RP) is a clinical condition that follows an exaggerated vasoconstriction of extremities in response to a cold or emotional stress. Microvascular dysfunction and alteration of the endothelial NO-dependent vasodilatation pathway through NO synthases (NOS) represents one of the main mechanisms.
A pharmacological treatment in RP is proposed to patients when conservative measures are not efficient enough to control the symptoms: calcium channel blockers remains the first line, phosphodiesterase type 5 inhibitors as a second line treatment, while intravenous iloprost remains restricted to patients with digital ischaemia. Vasodilator therapies are commonly associated with side effects due to the non-specific systemic vasodilation that often result in permanent discontinuation. Many patients prefer complementary and alternative therapies, but none has proven its efficacy. Therefore, there is still room for improvement in the treatment of RP, and research is needed in this area.
- Conditions
- Raynaud Phenomenon
- Being tested
- L-citrulline, Beetroot juice, L-citrulline placebo, Denitrated beetroot juice
- Keywords
- l-citrullin, beetroot juice, Raynaud's phenomenon
- Medical subject headings
- Raynaud Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-citrullineDietary supplement
L-citrulline 9g per day (capsule, per os) during 14 days;
Beetroot juiceDietary supplement
Concentrated 70 ml beetroot juice bottles containing 6.45 mmol of nitrates
L-citrulline placeboDietary supplement
L-citrulline placebo (maltodextrin) 9g per day (capsule, per os) during 14 days
Denitrated beetroot juiceDietary supplement
Concentrated 70 ml nitrate-depleted beetroot juice
| Study group | Role | What they receive |
|---|---|---|
| L-citrulline | Experimental | Six cycles will be conducted over two consecutive winters. One cycle will consist of two 2-week supplementation periods.
A 7 days wash-out period will be imposed between treatment periods (placebo and treatment). Receives: Dietary Supplement: L-citrulline |
| Beetroot juice | Experimental | Six cycles will be conducted over two consecutive winters. One cycle will consist of two 2-week supplementation periods.
A 7 days wash-out period will be imposed between treatment periods (placebo and treatment). Receives: Dietary Supplement: Beetroot juice |
| L-citrulline placebo | Placebo comparator | Six cycles will be conducted over two consecutive winters. One cycle will consist of two 2-week supplementation periods.
A 7 days wash-out period will be imposed between treatment periods (placebo and treatment). Receives: Dietary Supplement: L-citrulline placebo |
| Denitrated beetroot juice | Placebo comparator | Six cycles will be conducted over two consecutive winters. One cycle will consist of two 2-week supplementation periods.
A 7 days wash-out period will be imposed between treatment periods (placebo and treatment). Receives: Dietary Supplement: Denitrated beetroot juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Raynaud Condition Score
Change from baseline in the Raynaud's Condition score (RCS). RCS is participant's rating of difficulty considering number of attacks, duration, amount of pain, numbness, or other symptoms caused in the fingers (including painful sores) due to the Raynaud's phenomenon every day and impact of Raynaud's alone on use of hands every day. An 11 point Likert scale is used to rate the difficulty caused by the condition each day with 0 = no difficulty and 10 = extreme difficulty.
Measured: first winter: inclusion visit week 2, week 7, week 13, week 19; second winter: inclusion visit week 2,week 7, week 13, week 19
Frequency of RP
number of RP attacks during treatment, as compared to placebo
Measured: 7 days (An attack is defined as an episode of pallor or cyanosis (with or without pain,tingling or numbness). The number of attacks is self-reported every day and averaged over 7-day periods)
Change in cumulative attack duration
Mean duration of Raynaud's attacks for a time period was calculated as sum of recorded durations of attacks in the time period divided by total number of attacks in the time period where duration was recorded.
Measured: first winter: inclusion visit week 2, week 7, week 13, week 19; second winter: inclusion visit week 2,week 7, week 13, week 19
Secondary outcomes (5)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Mean duration of Raynaud's attacks for a time period was calculated as sum of recorded durations of attacks in the time period divided by total number of attacks in the time period where duration was recorded.
It will be assessed through adverse events collected in the daily dairies cards.
Measured: first winter: week 2, 4, 5, 7, 13, 19; second winter: week 2, 4, 5, 7, 13, 19
Plasma concentration of L-arginine/ADMA ratio
It will be quantified and compared under the 4 conditions.
Measured: first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7
Plasma concentration of nitrites
It will be quantified and compared under the 4 conditions.
Measured: first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7
Plasma concentration of L-arginine
It will be quantified and compared under the 4 conditions.
Measured: first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7
Urinary GMPc
It will be quantified and compared under the 4 conditions.
Measured: first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2018
- Study start1 Oct 2020
- Primary completion30 Apr 2022 (estimated)
- Study completion30 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Raynaud PhenomenonStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Rouen
- Responsible party
- Sponsor
- Investigators
- Jean-Luc Cracowski, MD, Principal investigator, Grenoble University Hospital, Clinical Pharmacology Department
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03749577
- Sponsor's protocol ID
- 38RC17.270
- Acronym
- NivOSe
- Status last verified
- May 2021
- First submitted
- 3 Jul 2018
- Last updated
- 14 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nutritional Strategies to Increase Nitric Oxide Signaling in Raynaud's Phenomenon
- ClinicalTrials.gov ID
- NCT03749577
- Acronym / sponsor ID
- NivOSe / 38RC17.270
- Conditions
- Raynaud Phenomenon
- Keywords
- l-citrullin, beetroot juice, Raynaud's phenomenon
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Collaborators
- University Hospital, Rouen
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 30 Apr 2022 (estimated)
- Study completion
- 30 Jun 2022 (estimated)
- First posted
- 21 Nov 2018 (actual)
- 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.
The investigators aim at comparing the efficacy of a 2 weeks supplementation by L-citrulline or beetroot juice to L-citrulline placebo or denitrated beetroot juice respectively on Raynaud's phenomenon severity. Raynaud's phenomenon severity will be assessed through the Raynaud Condition Score, daily frequency of attacks or cumulative attack duration (expressed as min) daily collected by patients in a diary. Each Volunteer will choose his own main outcome among these 3 criteria.
Detailed description
Raynaud's phenomenon (RP) is a clinical condition that follows an exaggerated vasoconstriction of extremities in response to a cold or emotional stress. Microvascular dysfunction and alteration of the endothelial NO-dependent vasodilatation pathway through NO synthases (NOS) represents one of the main mechanisms.
A pharmacological treatment in RP is proposed to patients when conservative measures are not efficient enough to control the symptoms: calcium channel blockers remains the first line, phosphodiesterase type 5 inhibitors as a second line treatment, while intravenous iloprost remains restricted to patients with digital ischaemia. Vasodilator therapies are commonly associated with side effects due to the non-specific systemic vasodilation that often result in permanent discontinuation. Many patients prefer complementary and alternative therapies, but none has proven its efficacy. Therefore, there is still room for improvement in the treatment of RP, and research is needed in this area.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| L-citrulline | Experimental | Dietary Supplement: L-citrullineSix cycles will be conducted over two consecutive winters. One cycle will consist of two 2-week supplementation periods. A 7 days wash-out period will be imposed between treatment periods (placebo and treatment). |
| Beetroot juice | Experimental | Dietary Supplement: Beetroot juiceSix cycles will be conducted over two consecutive winters. One cycle will consist of two 2-week supplementation periods. A 7 days wash-out period will be imposed between treatment periods (placebo and treatment). |
| L-citrulline placebo | Placebo comparator | Dietary Supplement: L-citrulline placeboSix cycles will be conducted over two consecutive winters. One cycle will consist of two 2-week supplementation periods. A 7 days wash-out period will be imposed between treatment periods (placebo and treatment). |
| Denitrated beetroot juice | Placebo comparator | Dietary Supplement: Denitrated beetroot juiceSix cycles will be conducted over two consecutive winters. One cycle will consist of two 2-week supplementation periods. A 7 days wash-out period will be imposed between treatment periods (placebo and treatment). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- BMI > 18
- Active Raynaud's Phenomenon characterized by a clinical history of Raynaud's
- Stable disease over the previous two months (i.e. recent diagnosis of SSc will be excluded)
- Patients insured by a social security scheme or beneficiaries of such a scheme
- Patients who have dated and signed the informed consent form
Key exclusion criteria (6 listed)
- Uncontrolled hypertension, uncontrolled diabetes mellitus, uncontrolled angina
- Haemodynamic instability
- Pregnancy (or considering pregnancy in next 4 months) or breast feeding
- Subject in an exclusion period from another study,
- Subject under administrative or judicial supervision
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 |
|---|---|---|
| L-citrullineL-citrulline 9g per day (capsule, per os) during 14 days; | Dietary supplement | L-citrulline |
| Beetroot juiceConcentrated 70 ml beetroot juice bottles containing 6.45 mmol of nitrates | Dietary supplement | Beetroot juice |
| L-citrulline placeboL-citrulline placebo (maltodextrin) 9g per day (capsule, per os) during 14 days | Dietary supplement | L-citrulline placebo |
| Denitrated beetroot juiceConcentrated 70 ml nitrate-depleted beetroot juice | Dietary supplement | Denitrated beetroot juice |
Primary outcome
Change in Raynaud Condition Score
Time frame: first winter: inclusion visit week 2, week 7, week 13, week 19; second winter: inclusion visit week 2,week 7, week 13, week 19
Change from baseline in the Raynaud's Condition score (RCS). RCS is participant's rating of difficulty considering number of attacks, duration, amount of pain, numbness, or other symptoms caused in the fingers (including painful sores) due to the Raynaud's phenomenon every day and impact of Raynaud's alone on use of hands every day. An 11 point Likert scale is used to rate the difficulty caused by the condition each day with 0 = no difficulty and 10 = extreme difficulty.
Frequency of RP
Time frame: 7 days (An attack is defined as an episode of pallor or cyanosis (with or without pain,tingling or numbness). The number of attacks is self-reported every day and averaged over 7-day periods)
number of RP attacks during treatment, as compared to placebo
Change in cumulative attack duration
Time frame: first winter: inclusion visit week 2, week 7, week 13, week 19; second winter: inclusion visit week 2,week 7, week 13, week 19
Mean duration of Raynaud's attacks for a time period was calculated as sum of recorded durations of attacks in the time period divided by total number of attacks in the time period where duration was recorded.
5 secondary outcomes
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: first winter: week 2, 4, 5, 7, 13, 19; second winter: week 2, 4, 5, 7, 13, 19
Plasma concentration of L-arginine/ADMA ratio
Time frame: first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7
Plasma concentration of nitrites
Time frame: first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7
Plasma concentration of L-arginine
Time frame: first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7
Urinary GMPc
Time frame: first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2021.
Related trials for Raynaud Phenomenon
Not yet recruitingPhase 2
A Study of LIQ861 (Inhaled Treprostinil) in Adults With Systemic Sclerosis Who Have Symptomatic Raynaud's Phenomenon Attacks
Raynaud's Phenomenon Secondary to Systemic Sclerosis
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.
Jean-Luc Cracowski, MD principal investigator
Grenoble University Hospital, Clinical Pharmacology Department
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-citrulline, Beetroot juice and Denitrated beetroot juice in people with Raynaud Phenomenon, 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 7 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 14 May 2021. 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. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Charles Khouri (+33 4 76 76 92 60, ckhouri@chu-grenoble.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Raynaud Condition Score (time frame: first winter: inclusion visit week 2, week 7, week 13, week 19; second winter: inclusion visit week 2,week 7, week 13, week 19). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 May 2021; AzTrials last refreshed its copy on 8 Nov 2026.