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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
30
L-citrulline 9g per day (capsule, per os) during 14 days;
Concentrated 70 ml beetroot juice bottles containing 6.45 mmol of nitrates
L-citrulline placebo (maltodextrin) 9g per day (capsule, per os) during 14 days
Grenoble University Hospital
Grenoble, France
RECRUITINGChange 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.
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
Frequency of RP
number of RP attacks during treatment, as compared to placebo
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)
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.
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
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.
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
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Concentrated 70 ml nitrate-depleted beetroot juice
It will be quantified and compared under the 4 conditions.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7