Characterization of the Role of Histamine in Children With Asthma

• Sponsor: Children's Mercy Hospital Kansas City (Other)
• Overall Status: Completed
• CT.gov ID: NCT01392859
• Collaborator: (none)
• Enrollment: 211
• Location: 1
• Arms: 2
• Duration (Months): 45.9
• Patients Per Site Per Month: 4.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma; Allergic Asthma; Non-allergic Asthma	Drug: Levocetirizine 0.5 Mg/mL Oral Solution	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 211 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Diagnostic
• Official Title: Characterization of the Role of Histamine in Children With Asthma
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Mar 29, 2015
• Actual Study Completion Date: Mar 29, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Initial Treatment: Levocetirizine(LCT) Group 1 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.	Drug: 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.
Experimental: Initial Treatment: Placebo Group 2 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.	Drug: 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.

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Mercy Hospital and Clinics	Kansas City	Missouri	United States	64131

Sponsors and Collaborators

• Children's Mercy Hospital Kansas City

Investigators

• Principal Investigator: Bridgette L. Jones, MD, Children's Mercy Hospital and Clinics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Children's Mercy Hospital Kansas City
• ClinicalTrials.gov Identifier: NCT01392859
• Other Study ID Numbers: 105783-01
• First Posted: Jul 13, 2011
• Last Update Posted: Aug 30, 2021
• Last Verified: Aug 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Asthma; Levocetirizine

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Initial Treatment: Levocetirizine First, Then Placebo	Initial Treatment: Placebo First, Then Levocetirizine	Laser Doppler Portion Only
Arm/Group Description	Only a small sub-set of the overall study participants were included in this analysis. Group 1 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. These participants also went through the laser doppler portion prior to the crossover portion of the study. 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.	Only a small sub-set of the overall study participants were included in this analysis. Group 2 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. These participants also went through the laser doppler portion prior to the crossover portion of the study. 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.	Participants who completed Only Laser Doppler portion of the study.
Period Title: Overall Study
STARTED	15	13	183
Wash Out 3-7 Days	15	13	0
COMPLETED	13	13	183
NOT COMPLETED	2	0	0

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	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.
Overall Participants	211
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	12.1 (3.1)
Sex: Female, Male (Count of Participants)
Female	90 42.7%
Male	121 57.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.5%
Asian	1 0.5%
Native Hawaiian or Other Pacific Islander	2 0.9%
Black or African American	74 35.1%
White	115 54.5%
More than one race	17 8.1%
Unknown or Not Reported	1 0.5%
Region of Enrollment (participants) [Number]
United States	211 100%

Outcome Measures

1. Primary Outcome

Title	Characterize Contribution of Histamine in Children With Asthma
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Overall Study
Arm/Group Description	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.
Measure Participants	211
Hyper-Reactive-	11253.24 (4271.17)
Normo-Reactive	6464.20 (1048.63)
Hypo-Reactive	3539.67 (1239.95)

Adverse Events

Arm/Group Title	Initial Treatment: Levocetirizine First, Then Placebo		Initial Treatment: Placebo First, Then Levocetirizine		Laser Doppler Portion Only
Arm/Group Description	Only a small sub-set of the overall study participants were included in this analysis. Group 1 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. These participants also went through the laser doppler portion prior to the crossover portion of the study. Note: Adverse Events (AE) were recorded by arm therefore AE's cannot be provided for each intervention separately. This data is no longer available to retrospectively separate AE's out by intervention.		Only a small sub-set of the overall study participants were included in this analysis. Group 2 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. These participants also went through the laser doppler portion prior to the crossover portion of the study. Note: Adverse Events (AE) were recorded by arm therefore AE's cannot be provided for each intervention separately. This data is no longer available to retrospectively separate AE's out by intervention.		Participants who completed Only Laser Doppler portion of the study.
All Cause Mortality
	Initial Treatment: Levocetirizine First, Then Placebo		Initial Treatment: Placebo First, Then Levocetirizine		Laser Doppler Portion Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/13 (0%)		0/183 (0%)
Serious Adverse Events
	Initial Treatment: Levocetirizine First, Then Placebo		Initial Treatment: Placebo First, Then Levocetirizine		Laser Doppler Portion Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/13 (0%)		0/183 (0%)
Other (Not Including Serious) Adverse Events
	Initial Treatment: Levocetirizine First, Then Placebo		Initial Treatment: Placebo First, Then Levocetirizine		Laser Doppler Portion Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/15 (60%)		6/13 (46.2%)		0/183 (0%)
Cardiac disorders
Chest Pain	1/15 (6.7%)	1	0/13 (0%)	0	0/183 (0%)	0
Gastrointestinal disorders
Nausea	3/15 (20%)	3	2/13 (15.4%)	2	0/183 (0%)	0
Diarrhea	1/15 (6.7%)	1	1/13 (7.7%)	1	0/183 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	1/15 (6.7%)	1	0/13 (0%)	0	0/183 (0%)	0
Nervous system disorders
Syncope	2/15 (13.3%)	2	1/13 (7.7%)	1	0/183 (0%)	0
Headache	1/15 (6.7%)	1	2/13 (15.4%)	2	0/183 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.