Alendronate to Prevent Loss of Bronchoprotection in Asthma

Status:	Completed
Conditions:	Asthma
Therapuetic Areas:	Pulmonary / Respiratory Diseases
Healthy:	No
Age Range:	18 - 80
Updated:	1/14/2018
Start Date:	January 2015
End Date:	September 2016

Proof of Concept Study of Alendronate for Asthma

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.

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 <80%, a minimum 12% increase in FEV1 post-bronchodilator or a MCh PC20 ≤ 8
mg/mL

- If FEV1 ≥80%, a MCh PC20 ≤ 8 mg/mL

- Salmeterol protected MCh ≤ 16 mg/mL

Exclusion Criteria:

- Uncontrolled asthma, as suggested by an ACT score <18 while on high-dose ICS (FP daily
dose >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

We found this trial at

sites

Wake Forest University Health Sciences

1 Medical Center Blvd
Winston-Salem, North Carolina 27157

336-716-2011