An Analysis of the Effect of Topical Cromolyn Sodium on Rosacea-associated Erythema

• ClinicalTrials.gov Identifier: NCT01933464
• Recruitment Status: Completed
• First Posted: September 2, 2013
• Results First Posted: July 30, 2019
• Last Update Posted: August 7, 2019
• Sponsor: University of California, San Diego
• Information provided by (Responsible Party): Anna Di Nardo, MD, PhD, University of California, San Diego

Study Description

Brief Summary:

This study is designed to investigate whether topical application of a cromolyn sodium solution is able to decrease the facial redness seen in patients with papulopustular rosacea. Previous work in the lab of Dr. Di Nardo on mice has suggested that cromolyn may be able to have this effect. The study will enroll a total of 10 patients. 5 will randomly be assigned to receive the cromolyn sodium solution, and the other 5 will be randomly assigned to receive the placebo solution. All participants will be instructed to apply their assigned solution twice daily to their face. Patients will return to the clinic 3, 6, and 8 weeks after the distribution of the solutions to measure the efficacy of their assigned solution.

Condition or disease	Intervention/treatment	Phase
Papulopustular Rosacea	Drug: Cromolyn Sodium; Drug: Normal Saline	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Analysis of the Effect of Topical Cromolyn Sodium on Rosacea-associated Erythema
• Actual Study Start Date: August 2013
• Actual Primary Completion Date: February 2014
• Actual Study Completion Date: April 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cromolyn; Subjects in this arm will be asked to apply their assigned medication twice daily to their entire face. The medication they will be receiving is cromolyn sodium ophthalmic solution, 4%.	Drug: Cromolyn Sodium; Other Name: Crolom
Placebo Comparator: Vehicle; Participants in this group will be assigned a solution consisting of only the inactive ingredients in cromolyn sodium ophthalmic solution to apply to their entire face twice daily.	Drug: Normal Saline; Other Names: 0.9% sodium chloride; NaCl

Outcome Measures

Primary Outcome Measures :

1. Facial Erythema [ Time Frame: Baseline ]
   Facial erythema will be measured using the Clinician's Erythema Assessment(CEA) applied to 5 areas of the subject's face (chin, nose, glabella, left cheek, right cheek), as well as using measurements from a colorimeter applied to each of the 5 locations previous mentioned. Each area is rated from 0-4, where 4 represents the most facial erythema (worst outcome). The scores for the 5 locations are summed with a CEA total score scale of 0-20.
2. Change in Facial Erythema [ Time Frame: Baseline and 8 weeks ]
   We will measure participants' change in facial erythema over the course of the study. The change in facial erythema is measured as a difference between the final (8 weeks after baseline) and baseline visit of the sum of the CEA scores determined from the 5 designated locations (nose, glabella, left cheek, right cheek, and chin). The scale range from -20 to 20. A negative score indicates improvement of facial erythema from baseline to 8 weeks after baseline. A positive score indicates worsening of facial erythema from baseline to 8 weeks after baseline.

Secondary Outcome Measures :

1. Matrix Metalloproteinase Activity Levels [ Time Frame: Baseline ]
   Tape stripping methods were used to isolate matrix metalloproteinase(MMP). Total-MMP activity was determined with total-MMP fluorogenic substrate (5 μM; Enzo Life Sciences), in protein extracts, and subsequently measuring activity (Vmax/sec) at a fluorescence excitation wavelength 328 nm and an emission wavelength of 400 nm in a fluorescence plate reader (Gemini EM microplate spectrofluorometer).
2. Change in Matrix Metalloproteinase Activity [ Time Frame: Baseline and 8 weeks ]
   We will compare subjects' matrix metalloproteinase activity levels at the beginning of the study (baseline) to those at the end of the study (8 weeks after baseline). Tape stripping methods were used to isolate matrix metalloproteinase(MMP). Total-MMP activity was determined with total-MMP fluorogenic substrate (5 μM; Enzo Life Sciences), in protein extracts, and subsequently measuring activity (Vmax/sec) at a fluorescence excitation wavelength 328 nm and an emission wavelength of 400 nm in a fluorescence plate reader (Gemini EM microplate spectrofluorometer).

Other Outcome Measures:

1. Adverse Events [ Time Frame: Baseline, and then 3, 6 and 8 weeks after beginning study intervention ]
   Adverse events will be recorded at each visit and their likelihood to the study interventions will be recorded

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subject is male or non-pregnant female, 18 - 80 years of age.
• Subjects willing and able to give informed consent.
• Subjects willing and able to comply with the requirements of the study.
• Subject has the clinical diagnosis of at least mild erythema.
• Subject has been on a stable dose for greater than 3 months of medications for treatment of concurrent medical condition (including oral contraceptive pills, vasodilators, adrenergic blocking agents) OR the investigator has determined that the medications are unlikely to affect the patient's rosacea and/or treatment during the study
• Subject is in general good health in the opinion of the investigator.

Exclusion Criteria:

• Subject has a diagnosis of Steroid Rosacea or Pyoderma Faciale (rosacea fulminans)
• Subject has a history of Carcinoid, Pheochromocytoma, Serotonin Syndrome or other systemic flushing causes.

Subject has used facial topical therapies (OTC drug products or prescription products) for any reason within the prior 28 days

• Subject has used systemic corticosteroid or systemic antibiotics (especially doxycycline, minocycline, tetracycline, metronidazole) within the prior 28 days.
• Subject has had laser or light-based treatment for rosacea within the prior 3 months.
• Subject has had systemic retinoids and retinoid derivatives over the past 6 months
• Subject has any history of renal or hepatic insufficiency.
• Subject has a known hypersensitivity or allergy to Cromolyn sodium or components of the vehicle.
• Subject is pregnant or lactating or planning a pregnancy during the duration of the study
• Subject has been treated with another investigational device or drug within 28 days prior to study enrollment or intends to participate in a clinical trial concurrent with this study
• Subject has clinically significant findings, medical history or conditions (other than rosacea), which in the opinion of the Investigator may compromise the study, treatment protocol, or safety of the patient or treatment allocation.

Subject has a known hypersensitivity or allergy to tape or other adhesive materials

Contacts and Locations

Locations

United States, California

UCSD Division of Dermatology

San Diego, California, United States, 92122

Sponsors and Collaborators

University of California, San Diego

More Information

• Responsible Party: Anna Di Nardo, MD, PhD, MD, PhD (Associate Professor of Medicine), University of California, San Diego
• ClinicalTrials.gov Identifier: NCT01933464
• Other Study ID Numbers: 130199
• First Posted: September 2, 2013
• Results First Posted: July 30, 2019
• Last Update Posted: August 7, 2019
• Last Verified: July 2019

Keywords provided by Anna Di Nardo, MD, PhD, University of California, San Diego:

Rosacea; Cromolyn sodium

Additional relevant MeSH terms:

Rosacea; Erythema; Skin Diseases; Skin Manifestations; Cromolyn Sodium; Mast Cell Stabilizers; Immunologic Factors; Physiological Effects of Drugs; Anti-Inflammatory Agents; Anti-Asthmatic Agents; Respiratory System Agents