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

NCT ID: NCT03749577

Last Updated: 2021-05-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2022-06-30

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.

Conditions

Raynaud Phenomenon

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

L-citrulline

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).

Group Type: EXPERIMENTAL

L-citrulline

Intervention Type: DIETARY_SUPPLEMENT

L-citrulline 9g per day (capsule, per os) during 14 days;

Beetroot juice

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).

Group Type: EXPERIMENTAL

Beetroot juice

Intervention Type: DIETARY_SUPPLEMENT

Concentrated 70 ml beetroot juice bottles containing 6.45 mmol of nitrates

L-citrulline placebo

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).

Group Type: PLACEBO_COMPARATOR

L-citrulline placebo

Intervention Type: DIETARY_SUPPLEMENT

L-citrulline placebo (maltodextrin) 9g per day (capsule, per os) during 14 days

Denitrated beetroot juice

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).

Group Type: PLACEBO_COMPARATOR

Denitrated beetroot juice

Intervention Type: DIETARY_SUPPLEMENT

Concentrated 70 ml nitrate-depleted beetroot juice

Interventions

L-citrulline

L-citrulline 9g per day (capsule, per os) during 14 days;

Intervention Type: DIETARY_SUPPLEMENT

Beetroot juice

Concentrated 70 ml beetroot juice bottles containing 6.45 mmol of nitrates

Intervention Type: DIETARY_SUPPLEMENT

L-citrulline placebo

L-citrulline placebo (maltodextrin) 9g per day (capsule, per os) during 14 days

Intervention Type: DIETARY_SUPPLEMENT

Denitrated beetroot juice

Concentrated 70 ml nitrate-depleted beetroot juice

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Rouen

OTHER

Sponsor Role: collaborator

University Hospital, Grenoble

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Luc Cracowski, MD

Role: PRINCIPAL_INVESTIGATOR

Grenoble University Hospital, Clinical Pharmacology Department

Locations

Grenoble University Hospital

Grenoble, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Charles Khouri

Role: CONTACT

ckhouri@chu-grenoble.fr

+33 4 76 76 92 60

Adeline Paris

Role: CONTACT

AParis@chu-grenoble.fr

+33 4 76 76 73 83

Facility Contacts

Charles Khouri, PharmD, PhD

Role: primary

ckhouri@chu-grenoble.fr

Other Identifiers

38RC17.270

Identifier Type: -

Identifier Source: org_study_id