A Histamine Pharmacodynamic Biomarker to Guide Treatment in Pediatric Asthma (HAS3)

NCT ID: NCT04699604

Last Updated: 2025-04-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-28
• Study Completion Date: 2026-05-01

Brief Summary

This is a randomized, double-blind, placebo-controlled, crossover study comparing asthma control post treatment in African American/Black and Caucasian/White children in both hyper and hypo responsive HILD (Histamine Lontophoresis with Laser Doppler monitoring) phenotypes with uncontrolled persistent allergic asthma using Levocetirizine (LTZ) vs placebo.

Detailed Description

The investigator hypothesizes that children with a hyper-responsive HILD (Histamine Lontophoresis with Laser Doppler monitoring) response type are more likely to have improved asthma control after the addition of the antihistamine LTZ (Levocetirizine) to standard asthma regimen in comparison to children with hypo-responsive HILD type. This study will provide a model for a functional biomarker to inform decision making for therapeutics in children. This work is novel in testing and validating a biomarker accurately and predicting response to asthma treatment in children. This work is significant because it has the potential to alter the current treatment paradigms for children with asthma where response to treatment is predicted a priority. The proposed research will be immediately relevant by expanding knowledge in the field of asthma therapeutics by linking biologically and mechanistically based approaches to an effective and inexpensive treatment for asthma. The primary objective is to determine HILD prediction of therapeutic response in males and females 6-17 years old who identify as African American/Black and Caucasian/White to an antihistamine among children with allergic asthma, and the secondary objective is to develop a robust predictive model of therapeutic response to an antihistamine among children with allergic asthma. There will be 300 participants for approximately 17 weeks.

The primary outcome measure of therapeutic response to antihistamine will be determined by change in asthma control as guidelines recognize asthma control as a major goal of therapy. Asthma control will be determined based on the Asthma Control Test (ACT®) (children ≥ 12 years of age) or the Child-Asthma Control Test (C-ACT®) (children <12 years of age), validated measures to assess asthma control in children. Children with an ACT or C-ACT score <19 will be classified as having uncontrolled asthma. Assessments will occur at screening, visit 2, 3 and 4 (6 weeks after the participant is started on drug/placebo.) The secondary measures will include assessment of asthma impairment, risk, and quality of life. These assessments will occur at baseline/pre-dose, 6 weeks after starting drug/placebo, and 6 weeks after drug/placebo for both the LTZ and placebo arms.

The study team is utilizing HILD a surrogate marker of histamine response and will determine if HILD can predict which participants have improvement in asthma control after treatment with Levocetirizine.

Conditions

Allergic Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Levocetirizine (LTZ)

Participants will take Levocetirizine dihydrochloride/ Xyzal® (UCB, Inc.) immediate release oral solution 2.5mg/5ml (2.5mg in children 6-11 years of age; 5mg in children \>11 years per recommended doses) in addition to their current asthma regimen.

Group Type: ACTIVE_COMPARATOR

Levocetirizine Dihydrochloride

Intervention Type: DRUG

At the end of the HILD assessment participants will be randomized to Levocetirizine Dihydrochloride or placebo. Children will be randomized by an investigational pharmacist to add-on either Levocetirizine dihydrochloride/ Xyzal® (UCB, Inc.) immediate release oral solution 2.5mg/5ml (2.5mg in children 6-11 years of age; 5mg in children \>11 years per recommended doses) or placebo to their current asthma regimen.

Placebo

Participants will take a placebo solution previously developed by the Children's Mercy Investigational Pharmacy to match the color, flavor, and consistency of the active drug in addition to their current asthma regimen.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Levocetirizine Dihydrochloride

At the end of the HILD assessment participants will be randomized to Levocetirizine Dihydrochloride or placebo. Children will be randomized by an investigational pharmacist to add-on either Levocetirizine dihydrochloride/ Xyzal® (UCB, Inc.) immediate release oral solution 2.5mg/5ml (2.5mg in children 6-11 years of age; 5mg in children \>11 years per recommended doses) or placebo to their current asthma regimen.

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Xyzal

Eligibility Criteria

Inclusion Criteria

1. A diagnosis of asthma based on physician diagnosis

2. A diagnosis of uncontrolled asthma based on Asthma Control Test (ACT) score within the last 3 months or at screening

3. Evidence of allergic sensitization based on allergy skin test or allergy blood test results

4. Individuals who are currently being treated with asthma guideline-based therapy

5. Males and females 6 through 17 years of age at time of enrollment

6. Willing to provide written permission/assent to participate

7. Children who self-identify as African American/black (identify both 1st degree (parents) and 2nd degree relatives (grandparents) as African American) or Caucasian/white (self-report of 1st and 2nd degree relatives as Caucasian)

Exclusion Criteria

1. For females, positive pregnancy test (by urinary hCG) or lactation at the time of the study

2. Any other chronic disease states such as history of premature lung disease, bronchiectasis, cystic fibrosis, or any chronic lung disease other than asthma.

3. Chronic abnormal conditions of the liver or kidney, immunologic/hematologic, or neoplastic disease as determined by the PI (the following questions will be asked at initial screening to identify children with potential abnormal kidney function:

Have you ever been diagnosed with chronic kidney disease?; Have you ever had to be on dialysis or take medications for chronic kidney disease?)

4. Inability or unwillingness to have blood drawn as described in the protocol schedule of events and consent, or inability or unwillingness to cooperate with study procedures.

5. Clinically significant abnormal safety laboratory values as determined by study physician

6. Previous history of adverse drug reaction to Levocetirizine (LTZ)

7. Unwillingness or inability to washout of medications that affect histamine response

8. Active eczema at the site where histamine laser doppler probe will be place(forearm) on the day of histamine laser doppler iontophoresis

9. Age 18 years or older at the time of enrollment.

10. Those whom are pregnant, prisoners, and/or wards of the state.

11. Currently on or has been on Tricyclic Antidepresants in past 30 days

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Bridgette Jones

OTHER

Sponsor Role: lead

Responsible Party

Bridgette Jones

Medical Director and Associate Professor of Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Darlene Brenson-Hughes, CCRC

Role: CONTACT

dbrensonhughes@cmh.edu

816-731-8376

Susan Flack, RN CCRC

Role: CONTACT

sflack@cmh.edu

816-960-8904

Facility Contacts

Darlene Brenson-Hughes

Role: primary

dbrensonhughes@cmh.edu

816.731.7386

Bridgette Jones, MD

Role: backup

bljones@cmh.edu

816-731-7072

Other Identifiers

5R01HD100545-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00001262

Identifier Type: -

Identifier Source: org_study_id