Alendronate to Prevent Loss of Bronchoprotection in Asthma

NCT ID: NCT02230332

Last Updated: 2018-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2016-09-30

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Alendronate

Alendronate in 10mg capsules taken once daily

Group Type: EXPERIMENTAL

Alendronate

Intervention Type: DRUG

Placebo

Placebo capsule taken once daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Alendronate

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Fasomax

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 <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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Milton S. Hershey Medical Center

OTHER

Sponsor Role: lead

Responsible Party

dave mauger

Professor of Public Health Sciences

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Juan Carlos Cardet, MD

Role: STUDY_DIRECTOR

Brigham and Women's Hospital

Locations

University of Arizona College of Medicine

Tucson, Arizona, United States

University of California - San Francisco

San Francisco, California, United States

National Jewish Health

Denver, Colorado, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

University of Illinois at Chicago

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

Cardet JC, Jiang X, Lu Q, Gerard N, McIntire K, Boushey HA, Castro M, Chinchilli VM, Codispoti CD, Dyer AM, Holguin F, Kraft M, Lazarus S, Lemanske RF, Lugogo N, Mauger D, Moore WC, Moy J, Ortega VE, Peters SP, Smith LJ, Solway J, Sorkness CA, Sumino K, Wechsler ME, Wenzel S, Israel E; AsthmaNet Investigators. Loss of bronchoprotection with ICS plus LABA treatment, beta-receptor dynamics, and the effect of alendronate. J Allergy Clin Immunol. 2019 Aug;144(2):416-425.e7. doi: 10.1016/j.jaci.2019.01.049. Epub 2019 Mar 11.

Reference Type: DERIVED

PMID: 30872116 (View on PubMed)

Related Links

http://asthmanetresearch.org/

AsthmaNet home page

Other Identifiers

U10HL098115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AsthmaNet 009

Identifier Type: -

Identifier Source: org_study_id