Clock Proteins as Prognostic Markers

NCT06302959 | Terminated

• 1 other identifier: 36-232 ex 23/24
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Severe Eosinophilic Asthma

Outcome Measures

Primary Outcomes (1)

• 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 \[mainly Forced expiratory volume 1 (FEV1) and FEV1/Forced vital capacity (FVC) ratio\].

  Up to three time points within 23 months.

Secondary Outcomes (1)

• Correlation between clock expression, symptoms and quality of life.

  Up to three time points within 23 months.

Study Arms (3)

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.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Graz: lead

Study Sites (1)

Medical University of Graz

Graz, Styria, 8010, Austria

Location

Related Publications (3)

• 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.

  PMID: 37314017 BACKGROUND

• Durrington 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.

  PMID: 23704227 BACKGROUND

• Carter 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.

  PMID: 26856993 BACKGROUND

MeSH Terms

Conditions

Pulmonary Eosinophilia

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Eva M Böhm, PhD

  Medical University of Graz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: March 12, 2024
• Study Start: May 1, 2024
• Primary Completion: September 9, 2025
• Study Completion: September 9, 2025
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)