Phase 3
N=78
Alendronate to Prevent Loss of Bronchoprotection in Asthma
Asthma
Bottom Line
View on ClinicalTrials.gov: NCT02230332 ↗Enrolled (actual)
78
Serious AEs
2.6%
Results posted
Dec 2017
Primary outcome: Primary: Salmeterol Protected Methacholine Challenge PC20 — 1.8; 1.7 mg/ml on log base 2 scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Alendronate (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Milton S. Hershey Medical Center
- Primary completion
- Sep 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Salmeterol Protected Methacholine Challenge PC20 |
1.8; 1.7 | — |
| SECONDARY Peripheral Blood Mononuclear Cell ADRB2 Cell Surface Density |
1680; 1863 | — |
| SECONDARY Beta-2 Adrenergic Receptor Agonist-induced cAMP Production |
5.9; 5.9 | — |
Summary
Beta-2-agonists are effective in reducing airway narrowing in asthma and protecting against stimuli that produce bronchoconstriction. The combination of long-acting beta agonists (LABA) and inhaled corticosteroids (ICS) has become the most commonly used asthma controller medication class in the United States, but unfortunately, even when LABAs are added to ICS and used regularly, 58-81% of patients with asthma fail to achieve total control. Regular use of beta-agonists, both short and long-acting, reduces the ability of these agents to protect against the airway narrowing that occurs in asthma in response to bronchoconstrictor stimuli. We refer to this reduced effect as loss of bronchoprotection. In this proof of concept trial we aim to determine if alendronate, which diminishes beta-2 adrenergic receptor internalization, can reduce the loss of bronchoprotection that occurs with regular use of LABAs, even when used in combination with ICS.
Eligibility Criteria
Inclusion Criteria
- Clinical history consistent with moderate asthma for >1 year
- Asthma is controlled with ICS, with an FP dose ≤ 1000mcg/day and >100mcg/day (or equivalent)
- Able to perform reproducible spirometry according to ATS criteria
- Baseline FEV1 ≥ 50% of predicted and ≥1L.
- If FEV1 500mcg or equivalent)
- Non-ICS controller medication or LABA use within 4 weeks of study entry.
- Contraindications to use of bisphosphonates: history of intolerance to bisphosphonates, history of esophageal ulcers, history of hematemesis, uncontrolled gastro-esophageal reflux disease, inability to stay erect for 30 minutes after oral drug, history of osteonecrosis of the jaw, dental extraction or root canal in prior 8 weeks, or anticipated during the study
- Calculated GFR of less than 35 mL/min
- History of smoking (cigarettes, cigars, pipes, marijuana or any other substances) within the past 1 year, or > 10 pack-years total if ≥ 18 years of age
- Systemic corticosteroid treatment for any condition within 4 weeks of enrollment at Visit 1, history of significant asthma exacerbation requiring systemic corticosteroids within 4 weeks of Visit 1 or more than five courses of systemic corticosteroids in the past year, history of a life-threatening asthma exacerbation requiring intubation, mechanical ventilation, or resulting in a hypoxic seizure within the last 2 years
- History of a respiratory tract infection within 4 weeks of Visit 1
- Receiving hyposensitization therapy other than an established maintenance regimen defined as a continuous regimen for ≥ 3 months prior to enrollment
Data sourced from ClinicalTrials.gov (NCT02230332). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.