AsthmaPhase 2/3ALFANCT02230332
Alendronate to Prevent Loss of Bronchoprotection in Asthma
A Phase 2/3 study testing Alendronate in people with Asthma, run by Milton S. Hershey Medical Center at 10 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Asthma
- What is being tested?
- Alendronate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 10 sitesUnited States
- Study dates
- Jan 2015to Sep 2016
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Brigham & Women's Hospital
Boston, Massachusetts, 02115
Northwestern Memorial Hospital
Chicago, Illinois, 60611
University of Illinois at Chicago
Chicago, Illinois, 60612
University of Chicago
Chicago, Illinois, 60637
National Jewish Health
Denver, Colorado, 80206
University of Wisconsin
Madison, Wisconsin, 53972
University of California - San Francisco
San Francisco, California, 94143
Washington University
St Louis, Missouri, 63110
University of Arizona College of Medicine
Tucson, Arizona, 85724
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: 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.
- Conditions
- Asthma
- Being tested
- Alendronate, Placebo
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlendronateDrug
Also called Fasomax
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Alendronate | Experimental | Alendronate in 10mg capsules taken once daily Receives: Drug: Alendronate |
| Placebo | Placebo comparator | Placebo capsule taken once daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 weeks after randomization
Secondary outcomes (2)
Peripheral Blood Mononuclear Cell ADRB2 Cell Surface Density
Measured: 8 weeks after randomization
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.
Measured: 8 weeks after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2014 (estimated)
- Study startJan 2015
- Primary completionSep 2016
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, dave mauger, Milton S. Hershey Medical Center
- Investigators
- Juan Carlos Cardet, MD, Study director, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02230332
- Sponsor's protocol ID
- AsthmaNet 009
- Other IDs
- U10HL098115
- Acronym
- ALFA
- Status last verified
- Dec 2017
- First submitted
- 29 Aug 2014
- Last updated
- 12 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30872116
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proof of Concept Study of Alendronate for Asthma
- ClinicalTrials.gov ID
- NCT02230332
- Acronym / sponsor ID
- ALFA / AsthmaNet 009
- Conditions
- Asthma
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jan 2015
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 3 Sep 2014 (estimated)
- Results
- Posted 14 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alendronate | Experimental | Drug: AlendronateAlendronate in 10mg capsules taken once daily |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo capsule taken once daily |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlendronateAlso: Fasomax | Drug | Alendronate |
| Placebo | Drug | Placebo |
Primary outcome
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.
2 secondary outcomes
Peripheral Blood Mononuclear Cell ADRB2 Cell Surface Density
Time frame: 8 weeks after randomization
Beta-2 Adrenergic Receptor Agonist-induced cAMP Production
Time frame: 8 weeks after randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30872116Cardet 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.
- AsthmaNet home pageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan Carlos Cardet, MD study director
Brigham and Women's Hospital
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Alendronate in people with Asthma, run by Milton S. Hershey Medical Center at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Salmeterol Protected Methacholine Challenge PC20 (time frame: 8 weeks after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02230332, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2018; AzTrials last refreshed its copy on 7 Nov 2026.