Tiotropium vs. Inhaled Corticosteroids in Children With Nonatopic Asthma Pilot Study (TioNAAP)

NCT04990167 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 1753113-1
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Most children with asthma have concurrent atopy (allergic inflammation), which is associated with an improved response to ICS. However, the absence of an atopic phenotype is associated with a poorer ICS response, leaving clinicians with limited treatment options. The nonatopic asthma phenotype has been characterized as the absence of atopic diseases including allergic rhinitis, eczema, or food allergies, and a negative skin prick test to common aeroallergens. Children with mild asthma treated with ICS over 44 weeks without a positive allergen skin test are 3 times more likely to have an asthma exacerbation when compared with children with positive skin tests. Similarly, adolescents and adults with asthma with low blood eosinophils or low sputum eosinophils have no difference in exacerbation rate response to ICS compared with placebo. Due to poor ICS response in nonatopic children and the known adverse effects of ICS, the development of non-steroid treatments options is needed. Monotherapy with the long-acting muscarinic antagonist, tiotropium, was superior to placebo for treatment failure outcomes in adolescents and adults with low sputum eosinophil levels. Tiotropium is approved in children as an add on therapy to ICS in children ≥ 6 years with asthma. But, this combination of treatment would still expose children with nonatopic asthma to the risks (but potentially without the benefit) of ICS therapy. The objective of this study is to conduct a feasibility pilot safety study of 6-weeks treatment with tiotropium monotherapy vs. ICS in children ages 6 to 11 years old with nonatopic mild persistent asthma.

Conditions

Asthma in Children

Keywords

Nonatopic

Outcome Measures

Primary Outcomes (1)

• Change in c-ACT score between standard therapy (inhaled corticosteroids) and tiotropium

  The primary outcome is change in asthma control from baseline to the end of 6-weeks treatment with tiotropium versus ICS. Asthma control will be assessed by the Childhood Asthma Control Test (c-ACT) score. The c-ACT is well validated for assessing asthma control in children aged 4-11 years.41 The c-ACT ranges from 0 to 27; a score of 19 indicates inadequately controlled asthma.

  The c-ACT will be collected during visit #1 in day 1; visit #2 after 6 weeks at the end of the first arm; visit #3 after 8 weeks at the end of the "wash-out period"; and visit #4 after 14 weeks at the last visit.

Secondary Outcomes (4)

• Spirometry FEV1

  The Spirometry FEV1 will be collected during visit #1 in day 1; visit #2 after 6 weeks at the end of the first arm; visit #3 after 8 weeks at the end of the "wash-out period"; and visit #4 after 14

• Fractional Exhaled Nitric Oxide (FeNO)

  The Fractional Exhaled Nitric Oxide (FeNO) will be collecte on day #1 duringf the first visit.

• Complete Blood Count with Differential (CBC)

  The Complete Blood Count with Differential (CBC) will be collecte on day #1 duringf the first visit.

• Daily Digital Diary

  The subjects will answer the Daily Digital Diary every day from day 1 until the completion of the study at 14 weeks.

Study Arms (2)

Tiotropium arm

EXPERIMENTAL

Subjects on this arm will start the study on tiotropium for 6 weeks. Received prescribed asthma controller medication for 2 weeks " washout" and complete 6 week on the prescribed asthma controller medication.

Drug: Tiotropium Bromide

ICS arm

ACTIVE COMPARATOR

Subjects on this arm will start the study on the prescribed asthma medication for 6 weeks. Received prescribed asthma controller medication for 2 weeks " washout" and complete 6 week on Tiotropium.

Drug: Tiotropium Bromide

Interventions

Tiotropium Bromide DRUG

Using Tiotropium as a single agent asthma controller medication

ICS arm; Tiotropium arm

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children ages 6 to 11 years with controlled mild nonatopic persistent physician diagnosed asthma
• Non-atopic asthma: absence of a positive SPT to inhaled aeroallergens or negative specific IgE to a common regional allergen panel; historical serum IgE less than 200 IU/ml; historical serum eosinophils less than 350 cells per microliter (cells/mcL); no history of eczema; no history of allergic rhinitis; no history of food allergy
• Physician-diagnosed asthma: positive family history, recurrent asthma symptoms, bronchodilator responsiveness, and evidence of obstruction.
• Mild persistent asthma: current treatment with as-needed albuterol or low-dose ICS or daily montelukast (Step 2 therapy)
• Controlled asthma: Childhood Asthma Control Test score \>19
• Pre-bronchodilator FEV1 ≥ 80% of predicted

You may not qualify if:

• Oral corticosteroid use in the past 6 weeks
• Use of ICS in combination with long-acting beta agonist or montelukast
• History of life-threatening asthma requiring treatment with intubation or mechanical ventilation within the past 5 years
• Respiratory tract infection within the past 4 weeks
• Any other chronic diseases or medical conditions (other than asthma) that in the opinion of the investigator would prevent participation in a trial

Sponsors & Collaborators

• Nemours Children's Clinic: lead

Study Sites (1)

Nemours Specialty Care

Jacksonville, Florida, 32207, United States

Location

MeSH Terms

Interventions

Tiotropium Bromide

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• Gerardo A Vazquez Garcia, MD

  Nemours

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Faculty Physician

Model Details: This is a prospective, randomized, open-label crossover pilot feasibility trial.

Study Record Dates

• First Submitted: June 17, 2021
• First Posted: August 4, 2021
• Study Start: January 1, 2022
• Primary Completion: October 31, 2025
• Study Completion: October 31, 2025
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

US (1)