Immunological Mechanisms in Sarcoidosis

Official title

Immunologiska Mekanismer Vid Sarkoidos

Overview

There is no cure for the inflammatory disease sarcoidosis. Virtually any part of the body can be affected but most often the lungs and lymph nodes. Outcomes after diagnosis vary widely among sarcoidosis patients, with some experiencing resolving disease and others developing chronic disease and lung fibrosis. Cardiac sarcoidosis can lead to life threatening arrythmias and calcium metabolism disturbances can lead to renal impairment. Treatment with different forms of immunosuppressants are usually tried to dampen symptoms but are not effective in all patients. Furthermore, the disease usually flares up after cessation of treatment. The variability in diseae course and treatment response is thought, at least to some degree, to be explained by individual differences in genetics, immune cells and signaling pathways. But existing evidence is limited. In other inflammatory diseases the gut microbiome is of importance for disease course but its role in sarcoidosis has not been clarified. In this prospective project the investigators will study genes, inflammatory cells and signaling molecules in the lung, upper airways and blood, and to some extent microbes, also in faeces. Healthy volunteers will be included for comparative studies. Most samples will be taken during normal diagnostic work-up and follow-up of patients with/with suspected sarcoidosis. The findings will be correlated to disease course and effects of different treatments. By linking to national health data and demographic registries, comorbidities and environmental factors will be correlated to data. By this, the investigators hope to improve understanding of which genes, cells and signaling molecules that are of importance for resolving vs non-resolving disease and why some patients respond to a certain treatment and others don´t. The overall goal is to assess and predict sarcoidosis outcomes. We hypothesize that blood-based biomarkers including those taken during routine care as well as novel cell, signaling molecules and genetic markers, in combination with clinical characteristics can be used to predict outcomes, also treatment response, in sarcoidosis. The results can lead to tailored treatment and individual follow-up for each patient with sarcoidosis.

Interventions

• Procedure peripheral blood sampling, bronchoscopy, upper airway and faeces sampling
  1. Repeated peripheral blood sampling at diagnostic and follow-up visits, in total a maximum of 400 ml/year but never more than 100 ml/ month. 2. Upper airway sampling wih swab, aspirate and curettage, maximum 3 times/year. 3. Faeces sampling, the patients do this themselves and leave it to the research unit, maximum 3 times/year. 4. Bronchoscopy with lavage and a maximum of 6 mucosal biopsies before and after 6-12 months treatment.

Primary outcome measures

• Disease activity [Time frame: 3 months and 12 months]
• Number of participants with resolving vs non-resolving disease [Time frame: 2 and 5 years from baseline]
• Number of participants with immunosuppressive treatment [Time frame: 5 years]
• Number of participants with more than 10% change from enrollment in percent of predicted Forced Expiratory Volume in one second (L/s) at 5 years [Time frame: Baseline and 5 years]
• Change from enrollment in Immunoglobulin G (g/L) at 5 years [Time frame: Baseline and 5 years]
• Change from enrollment in fatigue at 5 years [Time frame: Baseline and 5 years]
• Change from enrollment of radiographic findings at 5 years [Time frame: Baseline and 5 years]
• Change from enrollment of angiotensin converting enzyme (E/L) at 5 years [Time frame: Baseline and 5 years]
• Change from enrollment of soluble Interleukin Receptor 2 (U/ml) at 5 years [Time frame: Baseline and 5 years]
• Change from enrollment of complete blood cell count (/10x9 L) at 5 years [Time frame: Baseline and 5 years]

Eligibility criteria

Inclusion criteria

• Suspicion of sarcoidosis
• Swedish speaking
• Able to understand and approve of study protocol
• No contraindications for planned interventions
• For inclusion of healthy controls they need to be healthy and the same criteria as listed above for patients.

Exclusion criteria

• No suspicion of sarcoidosis
• Not Swedish-speaking
• Not able to understand study protocol
• Not approving of study protocol
• Contraindications for planned interventions

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

Sweden · 1 center

• Karolinska University Hospital — Stockholm

Identifiers

NCT: NCT06576505 · K2024-5925

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗