Atopic Dermatitis
Conditions
Keywords
Atopic dermatitis, Montelukast
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).
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.
Interventions
DRUGMontelukast 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.
DRUGPlacebo 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.
Sponsors
Merck Sharp & Dohme LLC
Pyun BokYang
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
2 Years to 6 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in SCORAD Index | 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) |
| Changes in Urinary LTE4 | 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. |
| Changes in Urinary EDN | 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. |
Countries
South Korea
Participant flow
Recruitment details
Childrens(2\ 6 years old) with moderate to severe atopic dermatitis recruited from the Pediatric Allergy and respiratory Center of the SoonChunHyang University Hospital (Seoul, Korea).
Pre-assignment details
54 participants recruited.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes groups randomized to receive Montelukast first and placebo first. | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Flu | 0 | 1 |
| First Intervention | Withdrawal by Subject | 5 | 3 |
| Second Intervention | Lost to Follow-up | 1 | 0 |
| Wash Out Period of 2 Weeks | Flu | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 46.0 months STANDARD_DEVIATION 16.1 |
| Severity of atopic dermatitis moderate | 26 participants |
| Severity of atopic dermatitis severe | 28 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 43 | 0 / 43 |
| serious Total, serious adverse events | 0 / 43 | 0 / 43 |
Outcome results
Primary
Changes in SCORAD Index
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)
Time frame: 18 weeks after patient recruitment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Montelukast Sodium | Changes in SCORAD Index | -3.0 units on a scale | Standard Deviation 11.2 |
| Placebo Drug | Changes in SCORAD Index | -5.7 units on a scale | Standard Deviation 11.3 |
Primary
Changes in Urinary EDN
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.
Time frame: 18 weeks after participants recruitment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Montelukast Sodium | Changes in Urinary EDN | 37.0 Urine EDN (ng/ml) | Standard Deviation 1008.6 |
| Placebo Drug | Changes in Urinary EDN | -195.8 Urine EDN (ng/ml) | Standard Deviation 916.7 |
Primary
Changes in Urinary LTE4
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.
Time frame: 18 weeks after patient recruitment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Montelukast Sodium | Changes in Urinary LTE4 | -65.9 Urinary LTE4 (pg/ml) | Standard Deviation 556.2 |
| Placebo Drug | Changes in Urinary LTE4 | 87.7 Urinary LTE4 (pg/ml) | Standard Deviation 618.3 |