Nutritional Strategies to Increase Nitric Oxide Signaling in Raynaud's Phenomenon

  • End date
    Jun 30, 2022
  • participants needed
  • sponsor
    University Hospital, Grenoble
Updated on 23 May 2021
nitric oxide
beetroot juice
raynaud's phenomenon


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.


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.

Condition Raynaud's Disease, Peripheral vascular disease, raynaud's phenomenon, raynaud phenomenon
Treatment Beetroot juice, L-citrulline, L-citrulline placebo, Denitrated beetroot juice
Clinical Study IdentifierNCT03749577
SponsorUniversity Hospital, Grenoble
Last Modified on23 May 2021


Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

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
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