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Alendronate to Prevent Loss of Bronchoprotection in Asthma (ALFA)

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ClinicalTrials.gov Identifier: NCT02230332
Recruitment Status : Completed
First Posted : September 3, 2014
Results First Posted : December 14, 2017
Last Update Posted : January 12, 2018
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
dave mauger, Milton S. Hershey Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Asthma Drug: Alendronate Drug: Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Proof of Concept Study of Alendronate for Asthma
Study Start Date : January 2015
Actual Primary Completion Date : September 2016
Actual Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: Alendronate
Alendronate in 10mg capsules taken once daily
Drug: Alendronate
Other Name: Fasomax

Placebo Comparator: Placebo
Placebo capsule taken once daily
Drug: Placebo

Primary Outcome Measures :
  1. Salmeterol Protected Methacholine Challenge PC20 [ Time Frame: 8 weeks after randomization ]
    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.

Secondary Outcome Measures :
  1. Peripheral Blood Mononuclear Cell ADRB2 Cell Surface Density [ Time Frame: 8 weeks after randomization ]
  2. Beta-2 Adrenergic Receptor Agonist-induced cAMP Production [ Time Frame: 8 weeks after randomization ]
    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.

Other Outcome Measures:
  1. Salivary Alpha Amylase Ratio (Post-Salmeterol / Pre-Salmeterol) [ Time Frame: 8 weeks after randomization ]
    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.

  2. Asthma Control Test (ACT) [ Time Frame: 8 weeks after randomization ]
    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.

  3. Fractional Exhaled Nitrix Oxide [ Time Frame: 8 weeks after randomization ]

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02230332

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United States, Arizona
University of Arizona College of Medicine
Tucson, Arizona, United States, 85724
United States, California
University of California - San Francisco
San Francisco, California, United States, 94143
United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
University of Chicago
Chicago, Illinois, United States, 60637
United States, Massachusetts
Brigham & Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53972
Sponsors and Collaborators
Milton S. Hershey Medical Center
National Heart, Lung, and Blood Institute (NHLBI)
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Study Director: Juan Carlos Cardet, MD Brigham and Women's Hospital
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: dave mauger, Professor of Public Health Sciences, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT02230332    
Other Study ID Numbers: AsthmaNet 009
U10HL098115 ( U.S. NIH Grant/Contract )
First Posted: September 3, 2014    Key Record Dates
Results First Posted: December 14, 2017
Last Update Posted: January 12, 2018
Last Verified: December 2017
Additional relevant MeSH terms:
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Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Bone Density Conservation Agents
Physiological Effects of Drugs