Alendronate to Prevent Loss of Bronchoprotection in Asthma

Asthma Clinical Trial

— ALFA  

Official title:

Proof of Concept Study of Alendronate for Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02230332
• Other study ID #: AsthmaNet 009
• Secondary ID: U10HL098115
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: August 29, 2014
• Last updated: December 13, 2017
• Start date: January 2015
• Est. completion date: September 2016

Study information

• Verified date: December 2017
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Alendronate

• Placebo

Locations

Country	Name	City	State
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	National Jewish Health	Denver	Colorado
United States	University of Wisconsin	Madison	Wisconsin
United States	Washington University	Saint Louis	Missouri
United States	University of California - San Francisco	San Francisco	California
United States	University of Arizona College of Medicine	Tucson	Arizona
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Salivary Alpha Amylase Ratio (Post-Salmeterol / Pre-Salmeterol)	Salivary Alpha Amylase (sAA) levels from saliva samples obtained through passive drooling, before and 1 hour after Salmeterol administration. The outcome is expressed as the ratio of the Post-Salmeterol to the Pre-Salmeterol sAA levels.	8 weeks after randomization
Other	Asthma Control Test (ACT)	Asthma Control Test : Score calculated as the sum total of a 5-item questionnaire. Each item ranges from 1 (poor control) to 5 (good control) so that the range of the total score is 5 to 25. Scores below 20 indicate that asthma is not well controlled.	8 weeks after randomization
Other	Fractional Exhaled Nitrix Oxide		8 weeks after randomization
Primary	Salmeterol Protected Methacholine Challenge PC20	Following administration of Salmeterol, the concentration of Methacholine required to produce a 20% drop in FEV1 - measured in mg/ml and reported on log base 2 scale.	8 weeks after randomization
Secondary	Peripheral Blood Mononuclear Cell ADRB2 Cell Surface Density		8 weeks after randomization
Secondary	Beta-2 Adrenergic Receptor Agonist-induced cAMP Production	Peripheral blood mononuclear cells cAMP concentrations measured using isoproterenol (ISO) as a beta-2 adrenergic receptor agonist, and using phosphate buffered saline (PBS) as a positive control. The outcome is expressed as the ratio of cAMP concentration using ISO relative to cAMP concentration using PBS.	8 weeks after randomization

External Links

•   AsthmaNet home page