Localized Effects of PBM and Exogenous NO on CREST Patients Calcinosis Cutis & Raynaud Phenomenon

NCT03972566 | Unknown

• 1 other identifier: NO-5420
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Background CREST is an acronym for the cardinal clinical features of the syndrome (Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia) and part of the heterogeneous group of sclerodermas. Calcinosis is the pathologic calcification of soft tissues. When symptomatic, they can be tender and painful, ulcerate, and drain a white chalky substance. With time, heterotopic bone formation may occur. Inflammatory reactions also intermittently occur at the site of calcinosis. It has been suggested that TGF-beta3 plays a major role in the pathogenesis of calcinosis. A variety of medical therapies have been used to try to alleviate patient symptoms. These include pharmacological approaches (e..g., warfarin), surgical curettage or excision, as well as carbon dioxide laser treatments. No consistently reliable pharmacological treatment seems to be available to prevent or eliminate calcinosis. Curettage and excision and carbon dioxide laser of localized painful large deposits can relieve symptoms but recurrence is common. In addition, aggressive curettage or excision can damage deeper neurovascular structures. While calcinosis is associated with significant morbidity its treatment remains a challenge. Photobiomodulation (PBM) has been shown to promote wound healing, suppress inflammatory reactions and regulate collagen synthesis in a number of in vitro and in vivo studies. Human skin contains photolabile nitric oxide (NO) derivatives which decompose after UVA irradiation and release vasoactive NO. However, aside from blue light, barely nothing has been reported about the effects of red and NIR wavelengths. Method A custom-built air tight sleeve which envelopes the forearm of a subject will be used to measure the NO emanating from the skin under photobiomodulation conditions (red \& NIR) and quantified by chemiluminescence detection. Simultaneously, CREST patient's hands exhibiting calcinosis and/or Raynaud phenomenon will be exposed to exogenous gaseous nitric oxide (INOMAX) to determine the vascular impact of this approach. This case series will assess Light Emitting Diode (LED) based PBM therapy as a treatment alternative for cutaneous calcinosis and the effects of gaseous NO on calcinosis and/or Raynaud phenomenon in CREST patients.

Conditions

CREST Syndrome; Calcinosis Cutis; Raynaud Phenomenon

Keywords

Nitric Oxide; Photobiomodulation; LLLT; Photomedicine

Outcome Measures

Primary Outcomes (2)

• Chemiluminescence detection

  Sievers Nitric Oxide Analyzer NOA 280i detects \[NO\] in Ambient Air or Solution

  15 minutes

• Endothelial Measurement

  VENDYS II

  5 minutes

Study Arms (2)

CREST with Calcinosis cutis

Drug: INOMAX

CREST without Calcinosis cutis

Drug: INOMAX

Interventions

INOMAX DRUG

INOMAX + PBM

CREST with Calcinosis cutis; CREST without Calcinosis cutis

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients suffering from CREST that have consulted in Dr. Barolet's Clinic of Dermatology

You may qualify if:

• Male or female
• years of age
• CREST syndrome with calcinosis cutis.
• CREST syndrome without calcinosis cutis.

You may not qualify if:

• Diabetes mellitus
• Acute inflammation
• Arrhythmia
• Acute malignancy
• Renal failure
• Active CVD
• Photodermatosis and/or photosensitivity including skin cancer-prone disease/syndrome (XP and Bloom Syndrome)
• Porphyria and/or hypersensitivity to porphyrins
• Congenital or acquired immunodeficiency.

Sponsors & Collaborators

• RoseLab Skin Optics Laboratory: lead
• Mallinckrodt: collaborator

Study Sites (1)

Clinique Dr Daniel Barolet

Laval, Quebec, H7T0G3, Canada

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Gaseous NO emanating from subject's arms, Digital Thermal Monitoring (DTM) to measure vascular reactivity

MeSH Terms

Conditions

CREST Syndrome; Calcinosis Cutis; Raynaud Disease

Interventions

Endothelium-Dependent Relaxing Factors

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Livedoid Vasculopathy; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Telangiectasis; Scleroderma, Limited; Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Skin Diseases, Vascular; Calcinosis; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Vasodilator Agents; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Daniel Barolet, MD

CONTACT

450-686-4744; daniel.barolet@mcgill.ca

Augustin Barolet, B.Eng

CONTACT

450-686-4744; augustin.barolet@mail.mcgill.ca

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: May 30, 2019
• First Posted: June 3, 2019
• Study Start: June 20, 2019
• Primary Completion: July 1, 2019
• Study Completion: September 1, 2019
• Last Updated: June 3, 2019

Record last verified: 2019-05

Locations

CA (1)