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

NCT03749577 | Unknown

• 1 other identifier: 38RC17.270
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Raynaud Phenomenon

Keywords

l-citrullin; beetroot juice; Raynaud's phenomenon

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (5)

• 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

• Plasma concentration of L-arginine/ADMA ratio

  first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7

• Plasma concentration of nitrites

  first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7

• Plasma concentration of L-arginine

  first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7

• Urinary GMPc

  first winter: week 2, 4, 5, 7; second winter: week 2, 4, 5, 7

Study Arms (4)

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).

Dietary Supplement: L-citrulline

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).

Dietary Supplement: Beetroot juice

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).

Dietary Supplement: L-citrulline placebo

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).

Dietary Supplement: Denitrated beetroot juice

Interventions

L-citrulline DIETARY_SUPPLEMENT

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

L-citrulline

Beetroot juice DIETARY_SUPPLEMENT

Concentrated 70 ml beetroot juice bottles containing 6.45 mmol of nitrates

Beetroot juice

L-citrulline placebo DIETARY_SUPPLEMENT

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

L-citrulline placebo

Denitrated beetroot juice DIETARY_SUPPLEMENT

Concentrated 70 ml nitrate-depleted beetroot juice

Denitrated beetroot juice

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI \> 18
• Active Raynaud's Phenomenon characterized by a clinical history of Raynaud's
• Primary RP or secondary to limited (LSSc), limited or diffuse cutaneous scleroderma (lcSSc or dcSSc) according to the criteria of Leroy and Medsger.
• 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

You may not qualify if:

• Uncontrolled hypertension, uncontrolled diabetes mellitus, uncontrolled angina
• Haemodynamic instability
• Pregnancy (or considering pregnancy in next 4 months) or breast feeding
• Subject under administrative or judicial supervision
• Subject not able to be contacted in case of emergency

Sponsors & Collaborators

• University Hospital, Grenoble: lead
• University Hospital, Rouen: collaborator

Study Sites (1)

Grenoble University Hospital

Grenoble, 38000, France

RECRUITING

MeSH Terms

Conditions

Raynaud Disease

Interventions

Citrulline

Condition Hierarchy (Ancestors)

Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Jean-Luc Cracowski, MD

  Grenoble University Hospital, Clinical Pharmacology Department

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2018
• First Posted: November 21, 2018
• Study Start: October 1, 2020
• Primary Completion: April 30, 2022
• Study Completion: June 30, 2022
• Last Updated: May 14, 2021

Record last verified: 2021-05

Locations

FR (1)