Severe Eosinophilic AsthmaCLOCK-PMNCT06302959
Clock Proteins as Prognostic Markers
An observational study of Severe Eosinophilic Asthma, run by Medical University of Graz at 1 site in Austria.
Trial summary
Asthma is a chronic inflammatory disease of the airways that follows a strong circadian rhythm: Signs of inflammation and symptoms worsen especially in the early morning hours. The molecular circadian clock, which is a complex machinery of transcriptional and translational feedback loops, seems to reflect the… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Severe Eosinophilic Asthma
- How many people
- 50 participants
- Where
- 1 siteAustria
- Study dates
- 1 May 2024to 9 Sep 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with mild-to-moderate or severe eosinophilic asthma and healthy controls will be recruited for this study. Three individual groups within an age-range of 18 to 65 years and a male:female ratio of 2:3 will be studied: 1. 20 age and gender matched healthy controls (1 visit) 2. 20 patients with mild-to-moderate asthma (1 visit) 3. 20-60 patients with SEA * before mepolizumab treatment (visit 1) * under mepolizumab treatment for 4 months (visit 2) * after reaching remission under mepolizumab treatment (visit 3)
Who may be able to join
- Written consent of the participant after being informed
- Age 18-65
- Both sexes (male:female ratio of 2:3)
- Mild-to-moderate asthma, severe eosinophilic asthma according to the "Global Initiative for Asthma" (GINA) guidelines and healthy controls
Who cannot join
- Respiratory tract infections during the last 2 months
- severe comorbidities
- oral corticosteroids during the last month
- Shift workers
- Subjects with sleep disorders and/or receiving sleep medication
- Pregnant or breast-feeding women
- Control subjects with atopy and/or allergies
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clock Proteins as a Prognostic Marker for Disease Progression
Asthma is a chronic inflammatory disease of the airways that follows a strong circadian rhythm: Signs of inflammation and symptoms worsen especially in the early morning hours. The molecular circadian clock, which is a complex machinery of transcriptional and translational feedback loops, seems to reflect the inflammatory environment of peripheral blood leukocytes. Therefore, in this observational study the investigators will monitor the molecular circadian clock in patients with severe eosinophilic asthma before and during mepolizumab treatment. Our major goal is to evaluate the potential of the molecular circadian clock to serve as a prognostic marker for disease progression, treatment response or remission in patients with severe eosinophilic asthma. The molecular circadian clock will be monitored in blood and sputum leukocytes from patients with severe eosinophilic asthma before mepolizumab treatment, after 4 month of mepolizumab therapy, and once they reach remission under mepolizumab treatment. Effects will be compared to healthy controls and patients with mild-moderate asthma without mepolizumab treatment.
Read the detailed description
Asthma is a heterogenous disease usually characterized by chronic airway inflammation that follows a strong circadian rhythm: Signs of inflammation and symptoms worsen especially in the early morning hours. Sudden death due to severe asthma attacks also tends to occur more frequently at night. Circadian rhythms are autonomous, self-sustained oscillations in biologic processes that follow a 24h-cycle and are entrained to environmental cues, the most important being light. At the cellular level, the circadian oscillator originates from a transcriptional/translational feedback loop comprised of several transcription factors and nuclear receptors.
Preliminary results indicate that the molecular circadian clock reflects the inflammatory environment of peripheral blood leukocytes. Thus, monitoring the molecular circadian clock will contribute to our understanding of asthma pathogenesis and treatment response and serve as a sensitive prognostic marker for disease progression and remission.
The primary objective of this observational study is to evaluate the potential of the molecular circadian clock to serve as a prognostic marker for disease progression, treatment response or remission. Therefore, the investigators will characterize the expression and activation of the molecular circadian clock components on the protein (flow cytometry) and messenger ribonucleic acid (mRNA) (quantitative polymerase chain reaction, qPCR) level in peripheral blood and sputum leukocyte subsets of healthy subjects, patients with mild-to-moderate asthma, patients with severe eosinophilic asthma (i) before and (ii) after 4 months of mepolizumab treatment, as well as (iii) after reaching remission under mepolizumab treatment. Results will be correlated with exacerbation rates and lung function parameters. As a secondary objective, the investigators will elucidate how the molecular circadian clock is regulated by the inflammatory environment and if anti-asthmatic drugs or therapeutic application of synthetic clock ligands may reverse the dysbalanced clock in asthma patients. Further, the investigators will assess the correlation between the expression and activation of the molecular circadian clock and the inflammatory state of the patients. Therefore, results will be correlated with patient's symptoms, quality of life and cytokine levels.
- Conditions
- Severe Eosinophilic Asthma
- Medical subject headings
- Pulmonary Eosinophilia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| healthy controls | For healthy controls, participation in this study lasts only one day. The following samples will be collected at three time-points on the same day (4 am, 12 pm, 8 pm): Blood sampling: 80 mL citrated whole blood and 10 mL serum will be collected. Collection of spontaneous sputum: at least 5 ml of sputum are collected. Saliva collection: Saliva is also collected at all three time-points. | |
| mild-to-moderate asthma | For patients with mild-to-moderate asthma, participation in this study lasts only one day. The following samples will be collected at three time-points on the same day (4 am, 12 pm, 8 pm): Blood sampling: 80 mL citrated whole blood and 10 mL serum will be collected. Collection of spontaneous sputum: at least 5 ml of sputum are collected. Saliva collection: Saliva is also collected at all three time-points. | |
| severe eosinophilic asthma | Patients with severe eosinophilic asthma, will be monitored (i) before mepolizumab treatment, (ii) after 4 months of mepolizumab treatment, (iii) once they reach remission under mepolizumab treatment. Mepolizumab is already approved for the treatment of severe eosinophilic asthma and is not administered for study purposes but as a standard treatment. On the day of participation, the following samples will be collected at three time-points (4 am, 12 pm, 8 pm): Blood sampling: 80 mL citrated whole blood and 10 mL serum will be collected. Collection of spontaneous sputum: at least 5 ml of sputum are collected. Saliva collection: Saliva is also collected at all three time-points. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between clock expression, exacerbation rate and lung function.
Expression and activation data from the molecular circadian clock will be corelated with the number of exacerbations within the last year and lung function parameters of the subjects [mainly Forced expiratory volume 1 (FEV1) and FEV1/Forced vital capacity (FVC) ratio].
Measured: Up to three time points within 23 months.
Secondary outcomes (1)
Correlation between clock expression, symptoms and quality of life.
Expression and activation data from the molecular circadian clock will be correlated with self-reported symptoms and quality of life. Quality of life will be assessed and scored by using a standardized Asthma Quality of life Questionnaire (AQLQ(S)), a 32-item questionnaire used to assess the physical, occupational, emotional, and social qualities of adults aged 17 to 70 years with asthma. Items are scored by a 7-point Likert scale (7 = not impaired at all; 1 = severely impaired). Thus, the AQLQ(S) has a minimum value of 32 (severely impaired) and a maximum value of 224 (not impaired).
Measured: Up to three time points within 23 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start1 May 2024
- Primary completion9 Sep 2025
- Study completion9 Sep 2025
Why it stopped: Recruitment failure
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Severe Eosinophilic AsthmaStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Graz
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eva M Böhm, PhD, Principal investigator, Medical University of Graz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06302959
- Sponsor's protocol ID
- 36-232 ex 23/24
- Acronym
- CLOCK-PM
- Status last verified
- Sep 2025
- First submitted
- 4 Mar 2024
- Last updated
- 3 Oct 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cunningham PS, Jackson C, Chakraborty A, Cain J, Durrington HJ, Blaikley JF. Circadian regulation of pulmonary disease: the importance of timing. Clin Sci (Lond). 2023 Jun 14;137(11):895-912. doi: 10.1042/CS20220061.
PubMed 37314017Durrington HJ, Farrow SN, Loudon AS, Ray DW. The circadian clock and asthma. Thorax. 2014 Jan;69(1):90-2. doi: 10.1136/thoraxjnl-2013-203482. Epub 2013 May 23.
PubMed 23704227Carter SJ, Durrington HJ, Gibbs JE, Blaikley J, Loudon AS, Ray DW, Sabroe I. A matter of time: study of circadian clocks and their role in inflammation. J Leukoc Biol. 2016 Apr;99(4):549-60. doi: 10.1189/jlb.3RU1015-451R. Epub 2016 Feb 8.
PubMed 26856993
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clock Proteins as a Prognostic Marker for Disease Progression
- ClinicalTrials.gov ID
- NCT06302959
- Acronym / sponsor ID
- CLOCK-PM / 36-232 ex 23/24
- Conditions
- Severe Eosinophilic Asthma
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Recruitment failure
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Medical University of GrazUniversity, hospital or other
- Study start
- 1 May 2024 (actual)
- Primary completion
- 9 Sep 2025 (actual)
- Study completion
- 9 Sep 2025 (actual)
- First posted
- 12 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Asthma is a chronic inflammatory disease of the airways that follows a strong circadian rhythm: Signs of inflammation and symptoms worsen especially in the early morning hours. The molecular circadian clock, which is a complex machinery of transcriptional and translational feedback loops, seems to reflect the inflammatory environment of peripheral blood leukocytes. Therefore, in this observational study the investigators will monitor the molecular circadian clock in patients with severe eosinophilic asthma before and during mepolizumab treatment. Our major goal is to evaluate the potential of the molecular circadian clock to serve as a prognostic marker for disease progression, treatment response or remission in patients with severe eosinophilic asthma. The molecular circadian clock will be monitored in blood and sputum leukocytes from patients with severe eosinophilic asthma before mepolizumab treatment, after 4 month of mepolizumab therapy, and once they reach remission under mepolizumab treatment. Effects will be compared to healthy controls and patients with mild-moderate asthma without mepolizumab treatment.
Detailed description
Asthma is a heterogenous disease usually characterized by chronic airway inflammation that follows a strong circadian rhythm: Signs of inflammation and symptoms worsen especially in the early morning hours. Sudden death due to severe asthma attacks also tends to occur more frequently at night. Circadian rhythms are autonomous, self-sustained oscillations in biologic processes that follow a 24h-cycle and are entrained to environmental cues, the most important being light. At the cellular level, the circadian oscillator originates from a transcriptional/translational feedback loop comprised of several transcription factors and nuclear receptors.
Preliminary results indicate that the molecular circadian clock reflects the inflammatory environment of peripheral blood leukocytes. Thus, monitoring the molecular circadian clock will contribute to our understanding of asthma pathogenesis and treatment response and serve as a sensitive prognostic marker for disease progression and remission.
The primary objective of this observational study is to evaluate the potential of the molecular circadian clock to serve as a prognostic marker for disease progression, treatment response or remission. Therefore, the investigators will characterize the expression and activation of the molecular circadian clock components on the protein (flow cytometry) and messenger ribonucleic acid (mRNA) (quantitative polymerase chain reaction, qPCR) level in peripheral blood and sputum leukocyte subsets of healthy subjects, patients with mild-to-moderate asthma, patients with severe eosinophilic asthma (i) before and (ii) after 4 months of mepolizumab treatment, as well as (iii) after reaching remission under mepolizumab treatment. Results will be correlated with exacerbation rates and lung function parameters. As a secondary objective, the investigators will elucidate how the molecular circadian clock is regulated by the inflammatory environment and if anti-asthmatic drugs or therapeutic application of synthetic clock ligands may reverse the dysbalanced clock in asthma patients. Further, the investigators will assess the correlation between the expression and activation of the molecular circadian clock and the inflammatory state of the patients. Therefore, results will be correlated with patient's symptoms, quality of life and cytokine levels.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| healthy controls | – | –For healthy controls, participation in this study lasts only one day. The following samples will be collected at three time-points on the same day (4 am, 12 pm, 8 pm): Blood sampling: 80 mL citrated whole blood and 10 mL serum will be collected. Collection of spontaneous sputum: at least 5 ml of sputum are collected. Saliva collection: Saliva is also collected at all three time-points. |
| mild-to-moderate asthma | – | –For patients with mild-to-moderate asthma, participation in this study lasts only one day. The following samples will be collected at three time-points on the same day (4 am, 12 pm, 8 pm): Blood sampling: 80 mL citrated whole blood and 10 mL serum will be collected. Collection of spontaneous sputum: at least 5 ml of sputum are collected. Saliva collection: Saliva is also collected at all three time-points. |
| severe eosinophilic asthma | – | –Patients with severe eosinophilic asthma, will be monitored (i) before mepolizumab treatment, (ii) after 4 months of mepolizumab treatment, (iii) once they reach remission under mepolizumab treatment. Mepolizumab is already approved for the treatment of severe eosinophilic asthma and is not administered for study purposes but as a standard treatment. On the day of participation, the following samples will be collected at three time-points (4 am, 12 pm, 8 pm): Blood sampling: 80 mL citrated whole blood and 10 mL serum will be collected. Collection of spontaneous sputum: at least 5 ml of sputum are collected. Saliva collection: Saliva is also collected at all three time-points. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with mild-to-moderate or severe eosinophilic asthma and healthy controls will be recruited for this study. Three individual groups within an age-range of 18 to 65 years and a male:female ratio of 2:3 will be studied: 1. 20 age and gender matched healthy controls (1 visit) 2. 20 patients with mild-to-moderate asthma (1 visit) 3. 20-60 patients with SEA * before mepolizumab treatment (visit 1) * under mepolizumab treatment for 4 months (visit 2) * after reaching remission under mepolizumab treatment (visit 3)
Key inclusion criteria (4 listed)
- Written consent of the participant after being informed
- Age 18-65
- Both sexes (male:female ratio of 2:3)
- Mild-to-moderate asthma, severe eosinophilic asthma according to the "Global Initiative for Asthma" (GINA) guidelines and healthy controls
Key exclusion criteria (7 listed)
- Respiratory tract infections during the last 2 months
- severe comorbidities
- oral corticosteroids during the last month
- Shift workers
- Subjects with sleep disorders and/or receiving sleep medication
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Correlation between clock expression, exacerbation rate and lung function.
Time frame: Up to three time points within 23 months.
Expression and activation data from the molecular circadian clock will be corelated with the number of exacerbations within the last year and lung function parameters of the subjects [mainly Forced expiratory volume 1 (FEV1) and FEV1/Forced vital capacity (FVC) ratio].
1 secondary outcome
Correlation between clock expression, symptoms and quality of life.
Time frame: Up to three time points within 23 months.
Results and safety
The study was stopped early (reason given: Recruitment failure). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2025.
- Background: PubMed 37314017Cunningham PS, Jackson C, Chakraborty A, Cain J, Durrington HJ, Blaikley JF. Circadian regulation of pulmonary disease: the importance of timing. Clin Sci (Lond). 2023 Jun 14;137(11):895-912. doi: 10.1042/CS20220061.
- Background: PubMed 23704227Durrington HJ, Farrow SN, Loudon AS, Ray DW. The circadian clock and asthma. Thorax. 2014 Jan;69(1):90-2. doi: 10.1136/thoraxjnl-2013-203482. Epub 2013 May 23.
- Background: PubMed 26856993Carter SJ, Durrington HJ, Gibbs JE, Blaikley J, Loudon AS, Ray DW, Sabroe I. A matter of time: study of circadian clocks and their role in inflammation. J Leukoc Biol. 2016 Apr;99(4):549-60. doi: 10.1189/jlb.3RU1015-451R. Epub 2016 Feb 8.
- Individual participant dataSharing planned: No
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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.
Eva M Böhm, PhD principal investigator
Medical University of Graz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Severe Eosinophilic Asthma, run by Medical University of Graz at 1 site in Austria.
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 4 inclusion and 7 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: stopped early, as of the sponsor's last update on 3 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Recruitment failure). Results are not available in the source record.
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?
Correlation between clock expression, exacerbation rate and lung function. (time frame: Up to three time points within 23 months.). 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 NCT06302959, which also lists 3 linked publications.
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 3 Oct 2025.