Tiotropium for Childhood Asthma

(TioNAAP Trial)

Overseen By Jennifer Gafford, RN

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Nemours Children's Clinic

Must not be taking: Oral corticosteroids, ICS with LABA

Disqualifiers: Life-threatening asthma, Respiratory infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for children with nonatopic asthma, a type of asthma not involving common allergies. Researchers compare tiotropium, a bronchodilator typically added to other asthma treatments, to standard steroid treatments to determine its effectiveness as a standalone option. The goal is to identify safer and more effective treatments for children with mild asthma unresponsive to steroids. Children aged 6 to 11 with mild nonatopic asthma and no history of eczema, allergic rhinitis, or food allergies may qualify for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot have used oral corticosteroids in the past 6 weeks or be using ICS with long-acting beta agonists or montelukast. You can continue using as-needed albuterol or low-dose ICS or daily montelukast.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that tiotropium is usually well-tolerated by children with asthma. Studies have found that it can help improve lung function and asthma control in kids and teens. Some children have experienced mild side effects like dry mouth or constipation, which are common with this type of medication.

Tiotropium is already approved for children aged 6 and older to use alongside other asthma treatments, indicating a level of safety. However, the current study examines its use as the sole treatment, which might lead to different results. Overall, past research suggests that tiotropium is safe enough to consider for children with asthma, but consulting a healthcare provider is always best. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for asthma?

Tiotropium is unique because it offers a new approach for treating childhood asthma by targeting the bronchial muscles to help them relax, which can lead to easier breathing. Unlike the standard inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs) that primarily address inflammation, tiotropium acts as a long-acting anticholinergic agent, providing an additional option for asthma management. Researchers are excited about tiotropium because it has the potential to improve lung function and reduce asthma symptoms in children who might not fully respond to existing treatments.

What evidence suggests that tiotropium might be an effective treatment for nonatopic asthma in children?

Research has shown that tiotropium can improve lung function and control asthma in children and teenagers. Studies have found that it reduces the frequency and severity of asthma attacks. Tiotropium is particularly beneficial for those with low levels of certain cells in their mucus, common in non-allergic asthma. It relaxes the muscles around the airways, easing breathing. This trial will compare tiotropium with standard inhaled corticosteroid (ICS) treatments. Tiotropium offers a promising non-steroid option for managing asthma in children, especially for those who do not respond well to inhaled steroid treatments and need alternative options. ^{1 4 5 6 7}

Who Is on the Research Team?

Gerardo A Vazquez Garcia, MD

Principal Investigator

Nemours

Are You a Good Fit for This Trial?

This trial is for children aged 6 to 11 with mild, controlled nonatopic asthma—meaning they don't have allergies like hay fever, eczema or food allergies and their blood tests show low levels of certain immune cells and antibodies. They should be currently treated with as-needed albuterol, low-dose inhaled steroids or daily montelukast.

Inclusion Criteria

My asthma is under control.

You do not have allergies or asthma triggered by specific allergens, and you do not have a history of eczema or food allergies. Your blood test results for allergy-related markers are also within specific ranges.

I manage my mild asthma with daily medication or as-needed inhaler.

Exclusion Criteria

I use a combination inhaler or montelukast for my asthma.

Any other chronic diseases or medical conditions (other than asthma) that in the opinion of the investigator would prevent participation in a trial

I have had severe asthma needing a breathing tube or machine in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Phase 1

Participants receive 6 weeks of treatment with either tiotropium or ICS

6 weeks

2 visits (in-person)

Washout

Participants undergo a 2-week washout period between treatments

2 weeks

1 visit (in-person)

Treatment Phase 2

Participants receive 6 weeks of treatment with the alternate therapy (tiotropium or ICS)

6 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Tiotropium Bromide

Trial Overview

The study compares tiotropium monotherapy—a long-acting inhaler medication—with inhaled corticosteroids (ICS) over a period of six weeks. It aims to see if tiotropium alone can manage asthma symptoms without the need for ICS in children who don't respond well to steroids due to lack of allergies.

How Is the Trial Designed?

Group I: Tiotropium arm Experimental Treatment 1 Intervention

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.

Group II: ICS arm Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Nemours Children's Clinic

Lead Sponsor

Trials

128

Recruited

18,000+

Published Research Related to This Trial

Tiotropium bromide is a safe and effective add-on treatment for children and adolescents aged 6-17 with moderate to severe asthma, even when they are already using inhaled corticosteroids.

Clinical trials have shown that once-daily tiotropium significantly helps manage asthma symptoms and reduces the risk of severe exacerbations in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium in the management of paediatric and adolescent asthma: Systematic review. Sunther, M., Marchon, K., Gupta, A.[2021]

In a study of 34 children aged 1-17 with severe asthma, tiotropium bromide was primarily used as a substitute therapy rather than an additional treatment, showing significant benefits in controlling symptoms like coughing and difficulty breathing.

Most physicians and parents reported improvements in asthma control and lung function, particularly in children with chronic symptoms, although some expressed concerns about potential adherence issues due to the need for an additional inhaler.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium bromide as adjunct therapy in children with asthma: a clinical experience. Ridha, Z., Bédard, MA., Smyrnova, A., et al.[2021]

In a pooled analysis of five studies involving 1691 pediatric patients aged 1-17 years, tiotropium (5 or 2.5 µg) was found to have a low incidence of adverse events (AEs), comparable to placebo, indicating it is a well-tolerated option for asthma management.

Tiotropium 5 µg significantly reduced asthma-related AEs and exacerbations compared to placebo, especially during peak seasons, suggesting it may provide effective symptom control in children with not fully controlled asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium add-on therapy is safe and reduces seasonal worsening in paediatric asthma patients. Vogelberg, C., Szefler, SJ., Vrijlandt, EJLE., et al.[2020]

In a study of 80 children with moderate persistent asthma, adding tiotropium to fluticasone propionate significantly improved lung function compared to fluticasone alone over 12 weeks.

Tiotropium also reduced the frequency of short-acting beta2-adrenoceptor agonist use and nighttime awakenings, with no severe adverse reactions reported, indicating it is a safe and effective option for managing asthma in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of tiotropium in children with asthma. Huang, J., Chen, Y., Long, Z., et al.[2022]

Tiotropium bromide (Spiriva® Respimat®) is the only long-acting muscarinic antagonist (LAMA) approved for use in children and adolescents with asthma, showing a bronchodilator effect that improves lung function compared to placebo.

Current evidence supports the efficacy of tiotropium in asthma management, but more well-designed studies are needed to establish a stepwise treatment approach and identify specific patient phenotypes that may benefit most from its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium Bromide in Children and Adolescents with Asthma. Raissy, HH., Kelly, HW.[2018]

Tiotropium Respimat® significantly improved lung function in children aged 6-11 with moderate-to-severe asthma, showing a peak FEV1 increase of 102 mL and a trough FEV1 increase of 82 mL compared to placebo, based on data from over 900 patients across three studies.

The treatment also led to a higher rate of asthma control (82.2% responders) and reduced the number of asthma exacerbations (29.1% vs. 39.8% with placebo), indicating its efficacy as an add-on therapy without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tiotropium in school-age children with moderate-to-severe symptomatic asthma: A systematic review. Rodrigo, GJ., Neffen, H.[2018]

In a 48-week phase III trial involving 398 adolescents aged 12 to 17, once-daily tiotropium significantly improved lung function, as measured by peak FEV1, compared to placebo, with the 5-μg dose showing greater improvement (174 mL) than the 2.5-μg dose (134 mL).

Tiotropium was found to be safe and well tolerated when used as an add-on treatment to inhaled corticosteroids, indicating its potential as an effective therapy for managing moderate symptomatic asthma in adolescents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial. Hamelmann, E., Bateman, ED., Vogelberg, C., et al.[2022]

Tiotropium bromide is a safe and effective long-acting muscarinic antagonist (LAMA) for treating uncontrolled asthma in children aged 6 to 17, even when they are already using inhaled corticosteroids.

There is a lack of research on the effects of tiotropium bromide in preschool children with asthma, highlighting a need for further studies in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Long-Acting Anticholinergics in Children and Adolescents With Difficult and Severe Asthma. Santamaria, F., Ziello, C., Lorello, P., et al.[2022]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5829125/

Efficacy and Safety of Tiotropium in Children ...

Findings from pooled analyses of phase III clinical trials in adolescents and children have shown improved lung function and asthma control where tiotropium ...

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1526054220301196

Review Tiotropium in the management of paediatric and ...

Recent clinical trials have demonstrated that once-daily tiotropium is safe and efficacious in 6–17 year-olds with symptomatic asthma despite treatment with ...

3.

aacijournal.biomedcentral.com

aacijournal.biomedcentral.com/articles/10.1186/s13223-021-00632-4

Tiotropium bromide as adjunct therapy in children with asthma

It appeared particularly effective in decreasing the severity and frequency of asthma exacerbations as well as diminishing chronic symptoms, ...

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annallergy.org

annallergy.org/article/S1081-1206(19)31460-7/fulltext

Tiotropium in children and adolescents with asthma

Once-daily tiotropium (5, 2.5, or 1.25 μg) improved lung function parameters, including peak and trough forced expiratory volume in 1 second, vs placebo.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT01383499

A Study to Evaluate Efficacy and Safety of Tiotropium in ...

A randomised dose-ranging study of tiotropium Respimat(R) in children with symptomatic asthma despite inhaled corticosteroids. Respir Res. 2015 Feb 7;16(1): ...

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/29361462/

Safety and efficacy of tiotropium in children aged 1-5 years ...

Our small study is the first to assess the safety and efficacy of tiotropium in children aged 1-5 years with persistent asthmatic symptoms.

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fda.gov

fda.gov/files/drugs/published/88_21936-tiotropium-clinical-prea.pdf

Clinical Review Tiotropium Clinical Review

efficacy and safety study in children ages 6 to 11 years with asthma who are symptomatic despite maintenance therapy with a stable medium-dose. ICS either ...