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| Name | Class |
|---|---|
| University Hospital, Rouen | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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). |
|
| 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). |
|
| 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-citrulline | Dietary Supplement | L-citrulline 9g per day (capsule, per os) during 14 days; |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 | 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. | first winter: inclusion visit week 2, week 7, week 13, week 19; second winter: inclusion visit week 2,week 7, week 13, week 19 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | first winter: week 2, 4, 5, 7, 13, 19; second winter: week 2, 4, 5, 7, 13, 19 |
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Inclusion Criteria:
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
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Charles Khouri | Contact | +33 4 76 76 92 60 | ckhouri@chu-grenoble.fr | |
| Adeline Paris | Contact | +33 4 76 76 73 83 | AParis@chu-grenoble.fr |
| Name | Affiliation | Role |
|---|---|---|
| Jean-Luc Cracowski, MD | Grenoble University Hospital, Clinical Pharmacology Department | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Grenoble University Hospital | Recruiting | Grenoble | 38000 | France |
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| ID | Term |
|---|---|
| D011928 | Raynaud Disease |
| ID | Term |
|---|---|
| D000090122 | Livedoid Vasculopathy |
| D013927 | Thrombosis |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D002956 | Citrulline |
| ID | Term |
|---|---|
| D000599 | Amino Acids, Diamino |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Beetroot juice |
| Dietary Supplement |
Concentrated 70 ml beetroot juice bottles containing 6.45 mmol of nitrates |
|
| L-citrulline placebo | Dietary Supplement | L-citrulline placebo (maltodextrin) 9g per day (capsule, per os) during 14 days |
|
| Denitrated beetroot juice | Dietary Supplement | Concentrated 70 ml nitrate-depleted beetroot juice |
|
| Plasma concentration of L-arginine/ADMA ratio | It will be quantified and compared under the 4 conditions. | 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. | 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. | 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. | first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7 |
| D002318 |
| Cardiovascular Diseases |
| D016491 | Peripheral Vascular Diseases |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |