The Effectiveness of Montelukast on Atopic Dermatitis in Koreans

• ClinicalTrials.gov Identifier: NCT00903357
• Recruitment Status: Completed
• First Posted: May 18, 2009
• Results First Posted: September 13, 2012
• Last Update Posted: December 14, 2015
• Sponsor: Pyun BokYang
• Collaborator: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Pyun BokYang, Soonchunhyang University Hospital

Study Description

Brief Summary:

The purpose of this study is to assess the clinical effectiveness of Montelukast in children (2~6 years old) with atopic dermatitis and identify the pathophysiologic background of Montelukast on the role of modulating the atopic dermatitis measured by urinary Leukotriene 4 (LTE4) and Eosinophil protein X(EDN).

Condition or disease	Intervention/treatment	Phase
Atopic Dermatitis	Drug: Montelukast first, then placebo; Drug: Placebo first, then Montelukast	Not Applicable

Detailed Description:

Leukotriene B4 (LTB4) and the cysteinyl-leukotrienes LTC4, LTD4 and LTE4 are potent proinflammatory mediators derived from arachidonic acid through the 5- lipoxygenase pathway. They are secreted from eosinophils and other inflammatory cells such as mast cells and macrophages. The primary action of leukotrienes includes contraction of human airway muscle, chemotaxis, and increased vascular permeability, with secondary effects of inhibiting allergen-induced early and late responses. Several in vivo and in vitro studies suggest a role for cysteinyl leukotrienes in the pathogenesis of atopic dermatitis and there is a rationale for the use of pharmacological agents to antagonize their effects in the treatment of atopic dermatitis. Levels of LTE4 measured in urine (Urinary-LTE4) may be a useful measure of whole-body cysteinyl-leukotriene production in vivo, because that LTE4 is a stable urinary metabolite of LTC4 and LTD4. Urinary-LTE4 has been measured in individuals with atopic dermatitis, but in small-scale studies, and the results are conflicting.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double Blind, Randomized, Crossover Study to Compare the Effectiveness of Montelukast on Atopic Dermatitis in Koreans
• Study Start Date: August 2009
• Actual Primary Completion Date: August 2010
• Actual Study Completion Date: April 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Montelukast first, then placebo; The group received active medication (montelukast 4 mg or 5mg once daily) for 8 weeks followed by a crossover to 8 weeks of placebo after 2-weeks washout period.	Drug: Montelukast first, then placebo; Patients in "Montelukast first, then placebo" will receive 4 mg of montelukast under the age of 6 years (5 mg of montelukast at 6 years) once daily for 8 weeks. And after 2 weeks wash-out period, they will receive chewable ascorbic acid placebo for 8 weeks. Patients in "Placebo first, then Montelukast" are received chewable ascorbic acid placebo for 8 weeks. And after 2 weeks wash-out period, they will receive 4 mg of montelukast under the age of 6 years (5 mg of montelukast at 6 years) once daily for 8 weeks.; Other Name: SINGULAIR; Drug: Placebo first, then Montelukast; Patients in "Montelukast first, then placebo" will receive 4 mg of montelukast under the age of 6 years (5 mg of montelukast at 6 years) once daily for 8 weeks. And after 2 weeks wash-out period, they will receive chewable ascorbic acid placebo for 8 weeks. Patients in "Placebo first, then Montelukast" are received chewable ascorbic acid placebo for 8 weeks. And after 2 weeks wash-out period, they will receive 4 mg of montelukast under the age of 6 years (5 mg of montelukast at 6 years) once daily for 8 weeks.; Other Name: Ascorbic acid
Experimental: Placebo first, then Montelukast; The group received placebo medication (ascorbic acid) for 8 weeks followed by a crossover to 8 weeks of active medication (montelukast 4 mg or 5mg once daily) after 2-weeks washout period.	Drug: Montelukast first, then placebo; Patients in "Montelukast first, then placebo" will receive 4 mg of montelukast under the age of 6 years (5 mg of montelukast at 6 years) once daily for 8 weeks. And after 2 weeks wash-out period, they will receive chewable ascorbic acid placebo for 8 weeks. Patients in "Placebo first, then Montelukast" are received chewable ascorbic acid placebo for 8 weeks. And after 2 weeks wash-out period, they will receive 4 mg of montelukast under the age of 6 years (5 mg of montelukast at 6 years) once daily for 8 weeks.; Other Name: SINGULAIR; Drug: Placebo first, then Montelukast; Patients in "Montelukast first, then placebo" will receive 4 mg of montelukast under the age of 6 years (5 mg of montelukast at 6 years) once daily for 8 weeks. And after 2 weeks wash-out period, they will receive chewable ascorbic acid placebo for 8 weeks. Patients in "Placebo first, then Montelukast" are received chewable ascorbic acid placebo for 8 weeks. And after 2 weeks wash-out period, they will receive 4 mg of montelukast under the age of 6 years (5 mg of montelukast at 6 years) once daily for 8 weeks.; Other Name: Ascorbic acid

Outcome Measures

Primary Outcome Measures :

1. Changes in SCORAD Index [ Time Frame: 18 weeks after patient recruitment ]
   Changes of SCORAD(SCORing Atopic Dermatitis) index after taking Montelukast or placebo drug. SCORAD calculation: Extent(%)/5 + 7*Intensity/2 + subjective symptoms (minimum score 0, maximum score 103) (SCORAD index >40: severe, 15-40:moderate, <15: mild)
2. Changes in Urinary LTE4 [ Time Frame: 18 weeks after patient recruitment ]
   Changes of Urinary LTE4(Leukotrien E4) after taking Montelukast or placebo drug. Urinary LTE4 levels were measured using an enzyme-linked immunoassay (ELISA) (Cayman Chemical, Michigan, USA) and the intra-assay and inter-assay variations were 7.4 ± 2.1 and 12.4 ± 7.8, respectively. Minimum value : 0 Maximum vlaue: 1000 pg/ml.
3. Changes in Urinary EDN [ Time Frame: 18 weeks after participants recruitment ]
   Changes of Urinary EDN(Eosinophil Derived Neurotoxin) after taking Montelukast or placebo drug. Urinary EDN levels were measured using an ELISA (MBL, Woburn, MA, USA) and the intra-assay and inter-assay variations were 3.0 ± 0.5 and 7.7 ± 1.5, respectively. Minimum value: 0, Maximum value: 2040 ng/ml.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 6 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• The ages of 2 to 6 years old, 54 children with moderate to severe atopic dermatitis diagnosed by the criteria of Haniffin and Rajka were included in the study.
• Volunteer children with moderate to severe atopic dermatitis were recruited from the Pediatric Allergy and respiratory Center of the SoonChunHyang University Hospital (Seoul, Korea). At the time of recruitment, written consent was obtained. The ethical committee at the SoonChunHyang University Hospital approved the trial.
• Volunteers who agreed by their parents.
• The severity of their disease was assessed by modified SCORAD index.

Exclusion Criteria:

• Too severe atopic dermatitis defined as the sum of scores is 80 and above by SCORAD index.
• A history of liver disease; allergy to montelukast or cross-reacting medication; use of phenobarbital, phenytoin or rifampicin.
• Patients on systemic steroids, immune-suppression or Korean herbal medicine during the previous 6 weeks.

Contacts and Locations

Locations

Korea, Republic of

Pediatric Allergy & Respiratory Center, Department of Pediatrics, Soonchunhyang University Hospital

Seoul, Korea, Republic of, 140-743

Sponsors and Collaborators

Pyun BokYang

Merck Sharp & Dohme Corp.

Investigators

• Study Chair: Bok Yang Pyun, M.D., PhD.; Pediatric Allergy & Respiratory Center, Department of Pediatrics, Soonchunhyang University Hospital

More Information

• Responsible Party: Pyun BokYang, Professor, Soonchunhyang University Hospital
• ClinicalTrials.gov Identifier: NCT00903357
• Other Study ID Numbers: schallergy
• First Posted: May 18, 2009
• Results First Posted: September 13, 2012
• Last Update Posted: December 14, 2015
• Last Verified: November 2015

Keywords provided by Pyun BokYang, Soonchunhyang University Hospital:

Atopic dermatitis; Montelukast

Additional relevant MeSH terms:

Dermatitis, Atopic; Dermatitis; Eczema; Skin Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Ascorbic Acid; Montelukast; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Molecular Mechanisms of Pharmacological Action; Antioxidants; Protective Agents; Vitamins; Micronutrients