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

Localized Effects of Photobiomodulation and Exogenous Nitric Oxide on CREST Patients Calcinosis Cutis & Raynaud Phenomenon

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.

Study Overview

• Status: Unknown
• Conditions: Calcinosis Cutis; Raynaud Phenomenon; CREST Syndrome
• Intervention / Treatment: Drug: INOMAX

• Study Type: Observational
• Enrollment (Anticipated): 5

Contacts and Locations

• Study Contact: Name: Daniel Barolet, MD; Phone Number: 450-686-4744; Email: daniel.barolet@mcgill.ca
• Study Contact Backup: Name: Augustin Barolet, B.Eng; Phone Number: 450-686-4744; Email: augustin.barolet@mail.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Laval, Quebec, Canada, H7T0G3
      • Clinique Dr Daniel Barolet
      • Contact: Daniel Barolet, MD; Phone Number: 450-686-4744; Email: daniel.barolet@mcgill.ca
      • Contact: Augustin Barolet, B.Eng; Phone Number: 450-686-4744; Email: augustin.barolet@mail.mcgill.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

• Male or female
• 18-60 years of age
• CREST syndrome with calcinosis cutis.
• CREST syndrome without calcinosis cutis.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CREST with Calcinosis cutis	Drug: INOMAX; INOMAX + PBM
CREST without Calcinosis cutis	Drug: INOMAX; INOMAX + PBM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chemiluminescence detection	Sievers Nitric Oxide Analyzer NOA 280i detects [NO] in Ambient Air or Solution	15 minutes
Endothelial Measurement	VENDYS II	5 minutes

Collaborators and Investigators

• Sponsor: RoseLab Skin Optics Laboratory
• Collaborators: Mallinckrodt

Study record dates

Study Major Dates

• Study Start (Anticipated): June 20, 2019
• Primary Completion (Anticipated): July 1, 2019
• Study Completion (Anticipated): September 1, 2019

Study Registration Dates

• First Submitted: May 30, 2019
• First Submitted That Met QC Criteria: May 31, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Actual): June 3, 2019
• Last Update Submitted That Met QC Criteria: May 31, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: LLLT; Photobiomodulation; Nitric Oxide; Photomedicine
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Skin Diseases; Gastrointestinal Diseases; Connective Tissue Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Calcium Metabolism Disorders; Peripheral Vascular Diseases; Scleroderma, Systemic; Telangiectasis; Scleroderma, Limited; Calcinosis; Raynaud Disease; CREST Syndrome
• Other Study ID Numbers: NO-5420

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No