An observational study in Severe Eosinophilic Asthma w/wo CRSwNP, sponsored by University of Crete. Recruiting at 2 sites in Greece. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-01-18.
Sponsored by University of Crete · Observational
Advances in understanding the pathophysiology of asthma development and severity have pointed towards a prominent role of the bronchial epithelium, especially in more chronic and severe disease. Studies suggest that airway eosinophilic inflammation in asthma is linked to epithelial injury and structural changes of the airways, co called airway wall remodeling. Together the chronic airway inflammation and remodeling are associated with bronchial hyperresponsiveness, fixed airflow obstruction or progressive loss of lung function and clinical severity of asthma. Chronic rhinosinusitis with nasal polyps (CRSwNP), is another respiratory inflammatory disease often co-existing with severe asthma, sharing similar pathophysiology. The investigators hypothesize that epithelial barrier integrity may play a role in the pathophysiology of severe eosinophilic asthma and nasal polyposis and in response to anti-IL5 therapy of severe asthmatics, and that shedding of epithelial barrier proteins may be used as biomarker in the management of severe asthma. In order to study that, the investigators will conduct a prospective cohort study of adult severe asthmatics with/out CRSwNP, who live on the island of Crete, Greece and who meet the criteria for entering anti-IL5 treatment, as assessed by pulmonologist. The participants will be recruited with a convenience sampling in a period of 2 years, under real life conditions, and will be followed up for 1 year after treatment initiation. A control group of subjects diagnosed with nasal polyposis without severe asthma will be used. Eligible subjects will undergo clinical assessment with radiological (CT) and endoscopic investigations. Samples of serum, sputum, nasal secretions, as well as nasal and bronchial biopsies will be obtain for assessing clinicopathological differences among the 3 groups but also response to anti-IL5 therapy in SEA w/o CRSwNP.
4,841 studies on the registry are indexed under Asthma; 600 are open to participants now.
This study's planned enrollment of 85 is below the median of 158 across 1,250 observational studies indexed under Asthma.
Browse Asthma studies →University of Crete is the lead sponsor of 23 studies on the registry; 6 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Adults with severe eosinophilic asthma, naive to anti-IL5/anti-IL5R treatment with or without CRSwNP who meet requirements for biologic therapy with anti-IL5 (Mepolizumab)
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Laboratory abnormality: No evidence of abnormality (other than those seen in SEA) in the haematological, biochemical or urinalysis screen at Visit 1, as judged by the investigator.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
control group; n\~20 of anti-IL5 naïve severe asthmatics
Drug: Mepolizumab 100 MG
n\~40 of anti-IL5 naïve severe asthmatics
Drug: Mepolizumab 100 MG
\~25;2nd control group
Patients with SEA eligible to receive anti-IL5 treatment, which is a biologic treatment for SEA
Differences in sputum columnar epithelial cells (CEPs) among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in sputum CEPs in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
We will employ flow cytometry on freshly isolated sputum cell suspensions from participants to measure CEPs proportion and count. Previously proposed cut-off value for normal range sputum CEP proportion (CEP % high = ≥11%) or number (CEP count high = ≥18.1 × 10\^4/mL) may be considered.
Time frame: Baseline and 1 year
Differences in E-cadherin protein level in sputum and nasal secretions among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in E-cadherin protein level in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
Soluble E-cadherin in sputum and nasal secretions measured with ELISA. Data will be expressed as nanograms per milliliter in original sputum/secretion. Cell surface expression of E-cadherin on columnar epithelial cells may be analyzed by flow cytometry.
Time frame: Baseline and 1 year
Differences in nasal and bronchial epithelial thickness among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in epithelial thickness in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
Epithelial thickness will be determined in biopsies by dividing the epithelial surface area by the basement membrane (BM) length
Time frame: Baseline and 1 year
Differences in nasal and bronchial epithelial integrity among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in epithelial integrity in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
Epithelial integrity will be assessed in biopsy sections and expressed as percentage (%) of BM covered with normal epithelium (a layer of basal and ciliated columnar epithelial cells without detachment from the BM)
Time frame: Baseline and 1 year
Differences in nasal and bronchial epithelial E-cadherin expression among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in protein expression in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
Epithelial E-cadherin expression in biopsies will be measure with immonohistochemistry and expressed as the percentage of BM covered with E-cadherin-positive intact epithelium and/or as strong, moderate and weak epithelial E-cadherin staining
Time frame: Baseline and 1 year
Differences in nasal and bronchial basement membrane thickness (BM) among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in Basement membrane thickness in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
BM thickness in biopsies will be expressed as BM surface area divided by BM length
Time frame: Baseline and 1 year
Differences in CT-assessed airway wall thickness (WT) among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in WT in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
We will use high resolution computer tomography of the chest to measureairway wall thickness (WT). Airway dimensions will be measured at on contiguous slices of the right apical segmental bronchus and right posterior basal segmental bronchus, from which tangential views of the bronchi can be obtained. The averaged values of the 2 bronchi will be used for analysis
Time frame: Baseline and 1 year
Differences in CRSwNP stage among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in CRSwNP stage in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
The Lund-Mackay score is widely used in radiological staging of chronic rhinosinusitis. Although there are many scoring systems in place for sinonasal computed tomography (CT) analysis, the Lund-Mackay system has the best inter- and intraob-server agreement. In LMK scoring, the sinuses (maxillary, anterior/posterior ethmoid, sphenoid, and frontal) are each scored on a scale of 0-2 opacification (0, normal; 1, partial opacification; 2, total opacification). The ostiomeatal complex is scored on a two-point scale of 0 and 2 (0, not occluded; 2, occluded). The scores on each side ranged from 0 (complete translucency of all sinuses) to 12 (complete opacity of all sinuses), leading to a total LMK score of 24 for both sides.Of note, an aplastic (absent) frontal sinus receives a score of 0.
Time frame: Baseline and 1 year
Differences in exacerbation rate among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in exacerbation rate in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
Number of exacerbation in the past 12 months. An exacerbation is defined as worsening of asthma requiring the use of systemic CS and/or emergency department visit, or hospitalisation. For subjects on maintenance oral corticosteroids, an exacerbation requiring oral CS is defined as the use of oral/systemic corticosteroids at least double the existing dose for at least 3 days
Time frame: Baseline and 1 year
Differences in lung function among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in lung function in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
FEV1 (liters and %predicted), FVC (liters and %predicted, FEV1/FVC (%) including pre and post bronchodilator test
Time frame: Baseline and 1 year
Differences in need for sinus surgery among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in need for sinus surgery in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
Number (%) of participants with a reduced need for sinus surgery at 1 year. Surgery will be deemed required with an ENP score of \>=3, or an ENP score of 2 and a TNSS score of \>7. Polyp (ENP) score: 0=No polyps,1=Small polyps in the middle meatus not reaching below the inferior border of the middle turbinate, 2=Polyps reaching below the lower border of the middle turbinate, 3=Large polyps reaching the lower border of the inferior turbinate or polyps medial to the middle turbinate, 4=Large polyps causing complete obstruction of the inferior nasal cavity. The higher of the two nostril scores will be derived and used for the analysis. With a VAS (0 to 10 cm) the severity of 4 nasal polyposis symptoms (one VAS for each symptom): rhinorrhea; mucus in the throat; nasal blockage; loss of smell, and for total nasal symptom score (TNSS). The left-hand side of the scale (0) represents "not troublesome," and the right-hand side of the scale (10) represents "worst possible troublesome.
Time frame: Baseline and 1 year
Differences in total IgE among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in total IgE in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
Total serum IgE (UI/ml)
Time frame: Baseline and 1 year
Differences in blood eosinophil count among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in blood eosninophil count in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
Blood eosinophil differential counts (number and percentage)
Time frame: Baseline and 1 year
Differences in sputum eosinophil count among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in sputum eosinophil count in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
Eosinophils count (number x10\^4/mL and %) in a differential cell count obtained from induced sputum
Time frame: Baseline and 1 year
Differences in FeNO among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in FeNO in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
Fractional Exhaled Nitric Oxide (FeNO in parts per billion)
Time frame: Baseline and 1 year
Differences in Asthma Control Test (ACT) among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in asthma control in1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
ACT includes 5 items, with 4-week recall (on symptoms and daily functioning). More specifically, ACT assesses the frequency of shortness of breath and general asthma symptoms, use of rescue medications, the effect of asthma on daily functioning, and overall self-assessment of asthma control. There is 5-point scale (for symptoms and activities: 1=all the time to 5= not at all; for asthma control rating: 1=not controlled at all to 5=completely controlled).The scores range from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control. An ACT score \>19 indicates well-controlled asthma.
Time frame: Baseline and 1 year
Differences in quality of life among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in quality of life in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
With the Asthma Quality of Life Questionnaire (AQLQ) we will assess quality of life and psychological morbidity. The Asthma Quality of Life Questionnaire (AQLQ) is a 32-item questionnaire used to assess the physical, occupational, emotional, and social qualities of adults aged 17 to 70 years with asthma (Juniper et al, 2005). The AQLQ has 4 domains: symptoms (12 items), activity limitation (6 generic and 5 patient-specific items), emotional function (5 items), and environmental stimuli (4 items). The AQLQ was developed for patients exhibiting mild to moderate asthma (Aburuz et al, 2007). The AQLQ items are each scored on a 7-point Likert scale, with 1 representing maximal impairment and 7 representing no impairment. The original AQLQ includes 5 patient-specific questions in the activity limitation domain. As part of the initial interview, the patient indicates 5 activity limitations due to asthma. These 5 activity limitations are used for the remaining follow-up visits.
Time frame: Baseline and 1 year
Differences in Asthma Control Questionnaire (ACQ) among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in asthma control in1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
ACQ has a multidimensional construct assessing symptoms (5 items--self-administred) and rescue inbronchodilator use (1 item-self-administered) with 1 week recall (for items on symptoms and rescue inhaler use), and FEV1% (1 item) completed by clinic staff. There is 7-point scale (0=no impairment, 6= maximum impairment for symptoms and rescue use; and 7 categories for FEV1%) and scores range between 0 (totally controlled) and 6 (severely uncontrolled). ACQ \>1.5 will be considered inadequately controlled asthma
Time frame: Baseline and 1 year
Differences in CT-assessed airway wall thickness percentage (WT%) among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in WT% in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
We will use high resolution computer tomography of the chest to measure the WT% calculated using the formula \[WT/outer dimaeter\] × 100), on contiguous slices of the right apical segmental bronchus and right posterior basal segmental bronchus, from which tangential views of the bronchi can be obtained. The averaged values of the 2 bronchi will be used for analysis
Time frame: Baseline and 1 year
Differences in CT-assessed percentage of wall area (WA%) among 3 groups (SEA w/o CRSwNP and CRSwNP with mild or no asthma) at baseline, and change in WA% in 1-year post anti-IL5 treatment initiation in SEA w/o CRSwNP
We will use high resolution computer tomography of the chest to measure the percentage of wall area (WA%) calculated using the formula \[airway wall area/outer area of the bronchus\] × 100), on contiguous slices of the right apical segmental bronchus and right posterior basal segmental bronchus, from which tangential views of the bronchi can be obtained. The averaged values of the 2 bronchi will be used for analysis
Time frame: Baseline and 1 year
Not enrolling at this site.
Plan to share: No
Started May 2022 (actual). Primary completion is estimated for May 2025, 36 months after the start.
Of 364 non-industry observational studies under Asthma, half reached primary completion within 38 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 97. This study's planned 36 months is close to that.
Counting every sponsor, half of 454 studies reached it within 36 months; a quarter within 18 and three quarters within 82.
How these figures are worked out, and which studies are left out of them.
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University of Crete