COPD and asthma
Conditions
Interventions
Trade Name: Azithromycin
Product Name: Azithromycin
Product Code: J01FA10
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the place
Sponsors
Lungemedicinsk Forskningsenhed
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All subjects 1. Written informed consent. 2. Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from the time informed consent is obtained and must agree to continue using such precautions through Week 14 of the study; cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause). Asthma patients (n=40) 1. Diagnosis of asthma according to GINA, with confirmed variable airflow obstruction at screening visit or previously (52). 2. Age =18 through 75 years. 3. FEV1 value of = 50% predicted. 4. Maintenance treatment with ICS and = 1 second controller (LABA, LAMA, LTRA or Xanthines) for at least three months prior to Visit 1. 5. Non-smokers (6 months). 6. = 1 Systemic steroid treated exacerbation in the past one year despite maintenance treatment with inhaled corticosteroids. 7. Eosinophilic (n=20, blood eosinophils = 0.200x109/L) and non-eosinophilic (n=20, blood eosinophils 6 months) 3. Normal spirometry (FEV1, FVC, FEV1/FVC ratio: all >LLN) 4. FeNO 45-75 years) subjects. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1.Previous medical history or evidence of an uncontrolled intercurrent illness that in the opinion of the investigator may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject’s ability to participate in the study. Subjects with well-controlled comorbid disease (eg, hypertension, hyperlipidemia, gastroesophageal reflux disease) on a stable treatment regimen for 15 days prior to Visit 1 are eligible. 2.Any concomitant respiratory disease that in the opinion of the investigator and/or medical monitor will interfere with the evaluation of the investigational product or interpretation of subject safety or study results (e.g., cystic fibrosis, pulmonary fibrosis, moderate-severe bronchiectasis, allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, active tuberculosis). In addition for the different groups the following: a.Patient with asthma: concomitant COPD. b.Patients with COPD: concomitant asthma (former and current) c.Healthy subjects: COPD and asthma. 3.Any clinically relevant abnormal findings in hematology or clinical chemistry (laboratory results from Visit 1), physical examination, vital signs during the screening, which in the opinion of the investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject’s ability to participate in the study. 4.Evidence of active liver disease, including jaundice or aspartate transaminase, alanine transaminase, or alkaline phosphatase >1.5 times the upper limit of normal (laboratory results from Visit 1). 5.GFR 1 day during the conduct of the study. 14.Unwillingness or inability to follow the procedures outlined in the protocol. 15.Concurrent enrollment in another clinical study involving an investigational treatment. 16.Receipt of any live or attenuated vaccines within 15 days prior to Visit 1. 17.Long QTc interval on ECG (QTc >480msec). 18.History of the following cardiac comorbidities: a.Life-threatening arrhythmias b.Myocardial infarction (NSTEMI or STEMI) less than 6 months before start of the study c.Unstable angina d.History of severe heart failure 19.Documented severe hypokalemia (K <3.0 mmol/L) or hypomagnesemia (Mg <0.5 mmol/L). 20.Life expectancy <6 months. 21.Hearing im
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether 12-weeks low dose AZM treatment improves antiviral defence in patients with asthma and COPD.;Secondary Objective: To investigate whether 12-weeks low dose AZM treatment improves the level of immunoreactivity in patients with asthma and COPD. To investigate whether 12-weeks low dose AZM treatment reduces markers of neutrophilic and eosinophilic airways inflammation in patients with asthma and COPD. To investigate if AZM-induced anti-viral and anti-inflammatory changes differ between disease phenotypes (such as eosinophilic and non-eosinophilic). To investigate whether 12-weeks low dose AZM treatment changes the lung microbiome abundance and profile. To investigate the effect of low dose AZM on biomarkers of airway inflammation. To investigate whether 12-weeks low dose AZM treatment changes the gut microbiome abundance and profile, and it’s relation to the respiratory microbiome. To investigate gene expression in airway epithelium using an unbiased approach before and after treatment. To investigate gene expression in lung mucosal biopsies using an unbiased approach before and after treatment. ;Primary end point(s): Primary end point: Change in HBEC IFN gene and/or protein expression in response to in vitro RV infection and viral mimics. Supportive primary objective: Change in viral load (RV16vRNA and/or TCID50 assay) in response to in vitro RV infection. ;Timepoint(s) of evaluation of this end point: At baseline (visit 1) and End of treatment (visit4) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change in HBEC gene and/or protein expression in response to in vitro stimulation with viral triggers, allergens, scratching of epithelium, and smoke exposure (or a combination of these triggers). Changes in markers of eosinophilic and neutrophilic inflammation (e.g. number and percentage of eosinophils and neutrophils, cytokines expression) in bronchial biopsies, sputum, BAL and blood. Level of FeNO. • Change in bronchial epithelial gene and/or protein expression in response to in vitro stimulation with viral triggers, allergens, scratching of epithelium, and smoke exposure, in eosinophilic (blood eosinophils >0.2x109/L) compared to non-eosinophilic patients. • Changes in BAL, bronchial biopsy and induced sputum inflammatory markers in eosinophilic (blood eosinophils >0.2x109/L) compared to non-eosinophilic patients. Changes in bronchial brush, BAL and induced sputum microbiome abundance and composition as measured by gene sequencing. Gene and protein expression in airway mucosa, airway epithelium, sputum and BAL. Including markers such as (but not limited to): TSLP, IL-33, TLRs, RIG-I like receptors, TH1 and TH2 cytokines. Changes in fecal microbiome abundance and composition as measured by gene sequencing. RNA seq will be performed and analyzed for (including but not limited to): • Transcripts most changed by AZM • Changes in genes known to be involved in epithelial cell dysfunction and/or asthma and COPD • Differences in epithelial gene expression between clinical phenotypes of asthma and COPD (e.g. eosinophilic vs non-eosinophilic) RNA seq will be performed and analyzed for (including but not limited to): • Transcripts most changed by AZM • Differences in epithelial gene expression between clinical phenotypes of asthma and COPD (e.g. eosinophilic vs non-eosinophilic) RNA seq will be performed and analyzed for (including but not limited to): • Transcripts most changed by AZM • Differences in epithelial gene expression between clinical | — |
Countries
Denmark
Contacts
Public ContactClinical trial
Lungemedicinsk Forskningsenhed
Outcome results
None listed