## Protocol Section
### Identification Module
**NCT ID:** NCT02183779

**Acronym:** REFRAIN

**Brief Title:** PORH and Response to Cold in Raynaud's Phenomenon.

**Official Title:** Rôle Des Acides Epoxy-eicosatriénoïques et du Monoxyde d'Azote Dans l'hyperhémie Post-occlusive cutanée Digitale et la réponse cutanée au Froid Dans le phénomène de Raynaud Primaire

#### Organization Study ID Info
**ID:** DCIC 14 02
#### Organization
**Class:** OTHER
**Full Name:** University Hospital, Grenoble
### Status Module
#### Completion Date
**Date:** 2017-06

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** RECRUITING
#### Last Update Post Date
**Date:** 2015-12-09

**Type:** ESTIMATED

**Last Update Submit Date:** 2015-12-08

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2016-10

**Type:** ESTIMATED

#### Start Date
**Date:** 2014-06

**Status Verified Date:** 2015-12

#### Study First Post Date
**Date:** 2014-07-08
**Type:** ESTIMATED
**Study First Submit Date:** 2014-07-01
**Study First Submit QC Date:** 2014-07-02
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University Hospital, Grenoble

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The main objective of the study is to determine if implication of epoxy-eicosatriénoïc acids (EETs) and NO during cutaneous post-occlusive hyperemia differs between patients with Raynaud phenomena and healthy volunteers, by studying hyperaemic postocclusive response after microinjection of fluconazole and L-NMMA at the dorsal side of the fingers.

**Detailed Description:** The main objective of the study is to determine if implication of epoxy-eicosatriénoïques acids (EETs) and NO during cutaneous post-occlusive hyperemia differs between patients with Raynaud phenomena and healthy volunteers, by studying hyperaemic postocclusive response after microinjection of fluconazole and L-NMMA at the dorsal side of the fingers.

Healthy controls and patients will undergo 3 visits

### Conditions Module

**Conditions:**

- Raynaud Disease

- Hyperemia

- Cold

**Keywords:**

- post-occlusive hyperaemia

- laser-speckle contrast imaging

- epoxyeicosatrienoic acid

- nitrous oxide

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** BASIC_SCIENCE

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** patients with reynaud phenomena

**Intervention Names:**

- Procedure: post-occlusive hyperemia

- Procedure: cooling box

- Drug: L-NMMA and Fluconazole dermic injection

**Label:** Reynaud

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Healthy volunteers

**Intervention Names:**

- Procedure: post-occlusive hyperemia

- Procedure: cooling box

- Drug: L-NMMA and Fluconazole dermic injection

**Label:** Healthy

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Healthy

- Reynaud

**Name:** post-occlusive hyperemia

**Type:** PROCEDURE

#### Intervention 2

**Arm Group Labels:**

- Healthy

- Reynaud

**Name:** cooling box

**Type:** PROCEDURE

#### Intervention 3

**Arm Group Labels:**

- Healthy

- Reynaud

**Name:** L-NMMA and Fluconazole dermic injection

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** post-occlusive hyperemia amplitude (maximal amplitude in % of maximal vasodilatation and AUC) in sites NaCl, fluconazole and L-NMMA (intradermal microinjection)

**Measure:** post occlusive hyperemia amplitude

**Time Frame:** day 1

#### Secondary Outcomes

**Description:** post-occlusive hyperemia amplitude (maximal amplitude in % of maximal vasodilatation and AUC) in sites NaCl, fluconazole and L-NMMA (intradermal microinjection) treated with anesthetic

**Measure:** post occlusive hyperemia amplitude with anesthetic treatment

**Time Frame:** day1

**Description:** cold-induced vasoconstriction amplitude (maximal amplitude in % of basal and AUC) in sites NaCl, fluconazole and L-NMMA (intradermal microinjection)

**Measure:** cold-induced vasoconstriction amplitude

**Time Frame:** day 2

**Description:** cold-induced vasoconstriction amplitude (maximal amplitude in % of basal and AUC) in sites NaCl, fluconazole and L-NMMA (intradermal microinjection) with anesthetic local treatment

**Measure:** cold-induced vasoconstriction amplitude with anesthetic treatment

**Time Frame:** day 2

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Neither raynaud's phenomenon or chronic disease for healthy volunteers
* Raynaud's phenomenon without connective tissue disease for patients in the group "Raynaud"

Exclusion Criteria:

* History of axillary dissection , trauma or surgery
* History of thromboembolic disease or thrombophilia
* Minor or law-protected major
* Exclusion period in another study
* No affiliation to medicare
* Pregnant, parturient or breasting woman
* Concomitant serious disease: progressive cancer, liver failure, history of myocardial infarction less than 5 years, angor
* Smoking in the 6 last months
* Person deprived of liberty by a legal or administrative decision, person under legal protection
* Maximal annual indemnification reached.

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** JLCracowski@chu-grenoble.fr

**Name:** Jean-Luc CRACOWSKI, MD-PhD

**Phone:** +33476769260

**Role:** CONTACT

**Contact 2:**

**Email:** MRoustit@chu-grenoble.fr

**Name:** Matthieu ROUSTIT, PharmD-PhD

**Phone:** +33476769260

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** GRENOBLE cedex9

**Contacts:**

***Contact 1:***

- **Email:** JLCracowski@chu-grenoble.fr

- **Name:** Jean-Luc CRACOWSKI, MD-PhD

- **Phone:** 33476769260

- **Role:** CONTACT

***Contact 2:***

- **Email:** AParis@chu-grenoble.fr

- **Name:** PARIS Adeline, PharmD-PhD

- **Phone:** 33476767383

- **Role:** CONTACT

***Contact 3:***

- **Name:** Jean-Luc CRACOWSKI, MD-PhD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** France

**Facility:** Centre d'investigation clinique CIC1406

**Status:** RECRUITING

**Zip:** 38043

#### Overall Officials

**Official 1:**

**Affiliation:** INSERM + University Hospital Grenoble

**Name:** Jean-Luc CRACOWSKI, MD-PhD

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000090122

- Term: Livedoid Vasculopathy

- ID: D000013927

- Term: Thrombosis

- ID: D000016769

- Term: Embolism and Thrombosis

- ID: D000016491

- Term: Peripheral Vascular Diseases

- ID: D000017445

- Term: Skin Diseases, Vascular

- ID: D000012871

- Term: Skin Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M14978

- Name: Respiratory Tract Infections

- Relevance: LOW

- As Found: Unknown

- ID: M9991

- Name: Hyperemia

- Relevance: HIGH

- As Found: Hyperemia

- ID: M14772

- Name: Raynaud Disease

- Relevance: HIGH

- As Found: Raynaud's Disease

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2750

- Name: Livedoid Vasculopathy

- Relevance: LOW

- As Found: Unknown

- ID: M16686

- Name: Thrombosis

- Relevance: LOW

- As Found: Unknown

- ID: M7784

- Name: Embolism

- Relevance: LOW

- As Found: Unknown

- ID: M19128

- Name: Embolism and Thrombosis

- Relevance: LOW

- As Found: Unknown

- ID: M29213

- Name: Peripheral Arterial Disease

- Relevance: LOW

- As Found: Unknown

- ID: M18894

- Name: Peripheral Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M19714

- Name: Skin Diseases, Vascular

- Relevance: LOW

- As Found: Unknown

- ID: T3486

- Name: Livedoid Vasculopathy

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000006940

- Term: Hyperemia

- ID: D000011928

- Term: Raynaud Disease

### Intervention Browse Module - Ancestors

- ID: D000000935

- Term: Antifungal Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000058888

- Term: 14-alpha Demethylase Inhibitors

- ID: D000065607

- Term: Cytochrome P-450 Enzyme Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000065088

- Term: Steroid Synthesis Inhibitors

- ID: D000006727

- Term: Hormone Antagonists

- ID: D000006730

- Term: Hormones, Hormone Substitutes, and Hormone Antagonists

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000065688

- Term: Cytochrome P-450 CYP2C9 Inhibitors

- ID: D000065689

- Term: Cytochrome P-450 CYP2C19 Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: Analg

- Name: Analgesics

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: VaDiAg

- Name: Vasodilator Agents

- Abbrev: Resp

- Name: Respiratory System Agents

### Intervention Browse Module - Browse Leaves

- ID: M12546

- Name: Nitrous Oxide

- Relevance: LOW

- As Found: Unknown

- ID: M18296

- Name: Fluconazole

- Relevance: HIGH

- As Found: Acute Lymphoblastic Leukemia

- ID: M12507

- Name: Nitric Oxide

- Relevance: LOW

- As Found: Unknown

- ID: M21301

- Name: omega-N-Methylarginine

- Relevance: LOW

- As Found: Unknown

- ID: M6252

- Name: Clotrimazole

- Relevance: LOW

- As Found: Unknown

- ID: M11796

- Name: Miconazole

- Relevance: LOW

- As Found: Unknown

- ID: M4254

- Name: Antifungal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M30537

- Name: Cytochrome P-450 Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: M9788

- Name: Hormone Antagonists

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000015725

- Term: Fluconazole

### Misc Info Module

- Version Holder: 2024-05-24
