AsthmaNet Proof of Concept Study of Alendronate for Asthma (ALFA) - Catalog

  • Name

    AsthmaNet Proof of Concept Study of Alendronate for Asthma (ALFA)

  • Accession Number

    HLB02222020a

  • Acronym

    AsthmaNet-ALFA

  • Related studies
  • BSI Study IDs

    AN1

  • Is public use dataset

    False

  • Keywords

    bisphosphonate; bronchoprotection; controller therapy; downregulation; loss of bronchoprotection; salmeterol; β(2)-Adrenergic receptor; β(2)-agonists

  • Ingestion Status
    Released
  • Has Study Datasets

    True

  • Has Specimens

    True

  • Specimen ID Type
    Coded
  • Study Website
  • The Framingham Heart Study Group requires that the requestor must obtain full or expedited IRB/Ethics Committee review and approval to obtain these data. Waivers or a determination that the research is exempt from ethical regulations do not suffice.

    False

  • Clinical Trial URLs
  • Study type
    Clinical Trial
  • Collection Type
    Open BioLINCC Study
  • Cohort type
    Adult
  • Interventions

    Drug: Alendronate

    Drug: Placebo

  • Study Open Date (Data)

    2020-04-01

  • Study Open Date (Specimens)

    2022-01-21

  • Date materials available

    2020-04-01

  • Last updated

    2022-01-21

  • Study period

    January 2015 – September 2016

  • Study Contacts
  • NHLBI Division

    DLD

  • Classification
    Lung
  • HIV study classification
    non-HIV
  • COVID study classification
    non-COVID
  • Pre-Website # of Specimens Shipped

    None

  • # of Returned Specimens

    None

  • Primary Publication URLs
  • Conditions
    Asthma
  • Objectives

    To determine whether alendronate can reduce long-acting β2-adrenergic receptor agonist-associated loss of bronchoprotection in inhaled corticosteroid–treated patients.

  • Background

    Long-acting β2-adrenergic receptor agonists (LABAs) can be used to supplement inhaled corticosteroids (ICSs) in asthma patients with inadequately controlled symptoms. However a significant portion of patients still do not obtain adequate control using this treatment strategy. This may be due to the loss of bronchoprotection (LOBP) that can occur with regular LABA use, meaning the treatment has diminished capacity to protect against airway narrowing in response to bronchoconstrictors. At the time of the ALFA study, the mechanism causing LOBP was unknown, but thought to be related to β2-adrenergic receptor (B2AR) downregulation through internalization, B2AR phosphorylation by G protein–coupled receptor (GPCR) kinases, and/or uncoupling from the adenylyl cyclase-mediated signaling pathway, among other mechanisms. Previous in vitro research has found that alendronate prevents both BA-induced internalization and loss of functional activation, and may preserve bronchoprotection against acetylcholine after long-term BA exposure. Therefore, the ALFA study hypothesized that alendronate would reduce LOBP occurrence in asthma patients treated with ICSs and regularly administered LABAs. The study also aimed to identify the mechanism responsible for LOBP, explore the role of exhaled nitric oxide in predicting LOBP, and investigate salivary α-amylase as a potential biomarker for B2AR dynamics.

  • Participants

    Adults with physician-diagnosed asthma were eligible to participate if they also met the following criteria: evidence of either bronchodilator reversibility (post-bronchodilator FEV1 ≥ 12%) or airway hyperresponsiveness (PC20 ≤ 8 mg/mL); FEV1 ≥ 50% of predicted and ≥ 1L; salmeterol-protected methacholine challenge (SPMCh) value < 16 mg/mL; and treated with stable ICS controller monotherapy for 4 or more weeks. 38 participants were enrolled in the alendronate treatment arm and 40 participants were enrolled in the placebo treatment arm.

  • Design

    ALFA was a 10-week, randomized, double-blind, placebo-controlled, parallel-arm trial. Eligible participants were treated with 250 μg of fluticasone propionate twice daily during a 2-week run-in period and then randomized to receive either 10 mg/d oral alendronate or placebo with 250 μg of fluticasone propionate and 50 μg of salmeterol in a combination Diskus device twice daily for 8 weeks during the treatment phase. Prior asthma treatments (including short-acting β2-adrenergic receptor agonists) were discontinued to prevent potential confounding on B2AR dynamics. Participants used 17 μg per puff of ipratropium as a primary rescue inhaler during the study. SPMCh was used to assess LOBP at randomization and after 8 weeks of treatment. The primary outcome was change in SPMCh PC20 value after 8 weeks of treatment expressed as logarithm base 2.

  • Conclusions

    This study did not find evidence that alendronate reduces LABA-associated LOBP. LOBP appears to be less common than presumed in concomitant ICS plus LABA-treated asthmatic patients.


    Cardet JC, Jiang X, Lu Q, et al. Loss of bronchoprotection with ICS plus LABA treatment, β-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.

  • Disease classification
  • Publications
  • Mat types
    DNA
    Plasma
  • Network
    AsthmaNet

The study population available in BioLINCC study data may be lower than total study enrollment due to Informed Consent restrictions and other factors.

  • Subjects

    78 subjects: 38 Alendronate/40 Placebo


    Last Modified: Jan. 26, 2022, 3:10 p.m.
  • Age
      Alendro Placebo All
    <20 . 2 2
    20-24 6 1 7
    25-29 7 9 16
    30-34 5 3 8
    35-39 4 7 11
    40-44 3 6 9
    45-49 6 4 10
    50-54 4 2 6
    55-59 . 2 2
    60-64 2 4 6
    65+ 1 . 1
     
     

    Last Modified: Jan. 26, 2022, 3:10 p.m.
  • Sex
      Alendro Placebo All
    Male 18 13 31
    Female 20 27 47
     

    Last Modified: Jan. 26, 2022, 3:10 p.m.
  • Race
      Alendro Placebo All
    Black 10 13 23
    White 24 21 45
    Hispanic/Latino 3 3 6
    Other 1 3 4
     

    Last Modified: Jan. 26, 2022, 3:10 p.m.

Please note that biospecimen availability is subject to review by the NHLBI, BioLINCC, and the NHLBI Biorepository. Certain biospecimens may not be made available for your request. PDF Section 3.0 of the BioLINCC Handbook describes the components of the review process.

  • Material Types

    Plasma
    DNA


    Last Modified: Jan. 26, 2022, 3:10 p.m.
  • General Freeze/Thaw Status

    100% of plasma samples have 0 thaws
    86% of DNA samples have 0 thaws


    Last Modified: Jan. 26, 2022, 3:10 p.m.
  • Visits (Vials)
      Plasma DNA Total
    Visit 2 371 331 702
    Visit 3 35 28 63
     

    Last Modified: Jan. 26, 2022, 3:10 p.m.
  • Visits (Subjects)
      Plasma
    Total number of subjects Average volume (ml) per subject
    Visit 2 54 10.56
    Visit 3 4 14.13

      DNA
    Total number of subjects Average mass (µg) per subject Average vials per subject
    Visit 2 48 143.87 6.90
    Visit 3 3 139.36 9.33

    Last Modified: Jan. 26, 2022, 3:11 p.m.