Allergic Asthma, Asthma, Non-allergic Asthma
Conditions
Brief summary
Asthma, a chronic disease which produces significant morbidity and mortality in children, is a significant health problem to a large segment of society. Despite considerable advances in the diagnosis and treatment of asthma over the past several years, a sizeable portion of patients do not respond to the core treatments. The investigators are now learning that the underlying pathophysiology of disease is different among patients with asthma therefore; treatments which are beneficial in some patient groups may be not achieve affect in other groups. Antihistamines have been studied in the past for the treatment of asthma. These studies have shown that there may be a beneficial effect of antihistamines in patients with allergic asthma where histamine likely plays a large role in disease and treatment response. However, there is not enough evidence to include these drugs in the standard treatment of asthma. The investigators hypothesize that histamine plays a definable, significant role in disease pathogenesis and treatment response in children with allergic asthma. The investigators plan to test this overall hypothesis through two specific aims. The first aim will characterize the relative contribution of histamine in allergic vs. non-allergic asthma. This aim will be accomplished by comparison of the microvasculature response to histamine in children with allergic asthma and children with non-allergic asthma, measured by histamine iontophoresis with laser Doppler (HILD) monitoring, to determine potential phenotype-associated differences in the pharmacodynamic response to histamine.
Interventions
DRUGLevocetirizine 0.5 Mg/mL Oral Solution
Subjects in two arms, will be enrolled in a classical, randomized, double blind, crossover, placebo controlled trial of Levocetirizine(LCT) with determination of the PD response to LCT as determined by suppression of histamine microvasculature response via HILD.
Sponsors
Children's Mercy Hospital Kansas City
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* children age 7-17 years old * with the diagnosis of allergic asthma or non-allergic asthma (n=102
Exclusion criteria
* history of immunodeficiency, mastocytosis * chronic abnormal conditions of the skin, liver or kidney * neoplastic disease * movement or neurologic disorders * active eczema on the forearms at the time of study * history of a previous anaphylactic episode * evidence of pregnancy (by urinary hCG) or lactation at the time of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterize Contribution of Histamine in Children With Asthma | one year | The investigators will compare the response to histamine via histamine iontophoresis with laser doppler monitoring (measured in flux units on a continuous scale)between subjects with allergic asthma compared to subjects with non-allergic asthma. |
Countries
United States
Participant flow
Pre-assignment details
211 total participants enrolled in the study including the laser doppler testing. Only a small sub-set (n=28) of these participants were included in the sub-study including Levocetirizine.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study 211 participants enrolled in overall study including laser doppler testing. Only 28 participants continued to subgroups below:
Group 1: Initial Treatment: Levocetirizine(LCT) will begin with active Levocetirizine(LCT) 0.5 mg/ml oral solution for 5-8 days. This arm will then undergo a 3-7 day washout period at which point crossover will occur and placebo will be provided for 5-8 days.
Levocetirizine 0.5 Mg/mL Oral Solution: Subjects in two arms, will be enrolled in a classical, randomized, double blind, crossover, placebo controlled trial of Levocetirizine(LCT) with determination of the PD response to LCT as determined by suppression of histamine microvasculature response via HILD.
Group 2: Initial Treatment: Placebo will begin with placebo oral solution for 5-8 days. This arm will then undergo a 3-7 day washout period at which point crossover will occur and active Levocetirizine(LCT) 0.5 mg/ml will be provided for 5-8 days.
Levocetirizine 0.5 Mg/mL Oral Solution: Subjects in two arms, will be enrolled in a classical, randomized, double blind, crossover, placebo controlled trial of Levocetirizine(LCT) with determination of the PD response to LCT as determined by suppression of histamine microvasculature response via HILD. | 211 |
| Total | 211 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 12.1 Years STANDARD_DEVIATION 3.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 74 Participants |
| Race (NIH/OMB) More than one race | 17 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 115 Participants |
| Region of Enrollment United States | 211 participants |
| Sex: Female, Male Female | 90 Participants |
| Sex: Female, Male Male | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 13 | 0 / 183 |
| other Total, other adverse events | 9 / 15 | 6 / 13 | 0 / 183 |
| serious Total, serious adverse events | 0 / 15 | 0 / 13 | 0 / 183 |
Outcome results
Primary
Characterize Contribution of Histamine in Children With Asthma
The investigators will compare the response to histamine via histamine iontophoresis with laser doppler monitoring (measured in flux units on a continuous scale)between subjects with allergic asthma compared to subjects with non-allergic asthma.
Time frame: one year
Population: Participants have been stratified based on their reactivity (i.e., participants with hyper-, normo-, or hypo-reactivity) and therefore the Number Analyzed for each Row differs from the Overall Number of Participants Analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study | Characterize Contribution of Histamine in Children With Asthma | Normo-Reactive | 6464.20 flux units on a continuous scale | Standard Deviation 1048.63 |
| Overall Study | Characterize Contribution of Histamine in Children With Asthma | Hypo-Reactive | 3539.67 flux units on a continuous scale | Standard Deviation 1239.95 |
| Overall Study | Characterize Contribution of Histamine in Children With Asthma | Hyper-Reactive- | 11253.24 flux units on a continuous scale | Standard Deviation 4271.17 |