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

Raynaud Phenomenon Clinical Trial

— NivOSe  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03749577
• Other study ID #: 38RC17.270
• Status: Recruiting
• Phase: N/A
• Start date: October 1, 2020
• Est. completion date: June 30, 2022

Study information

• Verified date: May 2021
• Source: University Hospital, Grenoble
• Contact: Charles Khouri
• Phone: +33 4 76 76 92 60
• Email: ckhouri[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 30, 2022
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Raynaud Disease
• Raynaud Phenomenon

Intervention

Dietary Supplement:
• L-citrulline
L-citrulline 9g per day (capsule, per os) during 14 days;
• Beetroot juice
Concentrated 70 ml beetroot juice bottles containing 6.45 mmol of nitrates
• L-citrulline placebo
L-citrulline placebo (maltodextrin) 9g per day (capsule, per os) during 14 days
• Denitrated beetroot juice
Concentrated 70 ml nitrate-depleted beetroot juice

Locations

Country	Name	City	State
France	Grenoble University Hospital	Grenoble

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Grenoble	University Hospital, Rouen

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Primary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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