Raynaud Phenomenon
Conditions
Keywords
l-citrullin, beetroot juice, Raynaud's phenomenon
Brief 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. 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.
Interventions
DIETARY_SUPPLEMENTL-citrulline
L-citrulline 9g per day (capsule, per os) during 14 days;
DIETARY_SUPPLEMENTBeetroot juice
Concentrated 70 ml beetroot juice bottles containing 6.45 mmol of nitrates
DIETARY_SUPPLEMENTL-citrulline placebo
L-citrulline placebo (maltodextrin) 9g per day (capsule, per os) during 14 days
DIETARY_SUPPLEMENTDenitrated beetroot juice
Concentrated 70 ml nitrate-depleted beetroot juice
Sponsors
University Hospital, Rouen
University Hospital, Grenoble
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* BMI \> 18 * Active Raynaud's Phenomenon characterized by a clinical history of Raynaud's 1. Primary RP or secondary to limited (LSSc), limited or diffuse cutaneous scleroderma (lcSSc or dcSSc) according to the criteria of Leroy and Medsger. 2. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Raynaud Condition Score | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentration of L-arginine | first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7 | It will be quantified and compared under the 4 conditions. |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | first winter: week 2, 4, 5, 7, 13, 19; second winter: week 2, 4, 5, 7, 13, 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. It will be assessed through adverse events collected in the daily dairies cards. |
| Urinary GMPc | first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7 | It will be quantified and compared under the 4 conditions. |
| Plasma concentration of L-arginine/ADMA ratio | first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7 | It will be quantified and compared under the 4 conditions. |
| Plasma concentration of nitrites | first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7 | It will be quantified and compared under the 4 conditions. |
Countries
France
Contacts
Primary ContactCharles Khouri
Backup ContactAdeline Paris
Outcome results
None listed