Clinical trial NCT06576505: Immunological Mechanisms in Sarcoidosis
Official title: Immunologiska Mekanismer Vid Sarkoidos
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Sarcoidosis
Lead sponsor: Region Stockholm
Sponsor class: OTHER_GOV
Collaborators: name: Karolinska Institutet
First posted: 2024-08-28
Enrollment: 5000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with/with a suspicion of sarcoidosis referred to Department of Respiratory Medicine, Karolinska University Hospital, Stockholm, Sweden. A total of 4600 patients are planned to be included during 10 years (460/year).

Healthy volunteers will be recruited through advertisments (web based platforms within Karolinska Institutet, magazines, notice-boards). A total of 400 are planned to be included during 10 years (40/year).

Brief summary: 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.


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

Primary outcomes:
measure: Disease activity
timeFrame: 3 months and 12 months
measure: Number of participants with resolving vs non-resolving disease
timeFrame: 2 and 5 years from baseline
measure: Number of participants with immunosuppressive treatment
timeFrame: 5 years
measure: 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
timeFrame: Baseline and 5 years
measure: Change from enrollment in Immunoglobulin G (g/L) at 5 years
timeFrame: Baseline and 5 years
measure: Change from enrollment in fatigue at 5 years
timeFrame: Baseline and 5 years
measure: Change from enrollment of radiographic findings at 5 years
timeFrame: Baseline and 5 years
measure: Change from enrollment of angiotensin converting enzyme (E/L) at 5 years
timeFrame: Baseline and 5 years
measure: Change from enrollment of soluble Interleukin Receptor 2 (U/ml) at 5 years
timeFrame: Baseline and 5 years
measure: Change from enrollment of complete blood cell count (/10x9 L) at 5 years
timeFrame: Baseline and 5 years
measure: Change from enrollment of creatinine levels (micromol/L) at 5 years
timeFrame: Baseline and 5 years
measure: Change from enrollment of C-reactive protein (mg/L) at 5 years
timeFrame: Baseline and 5 years
measure: Number of patients with more than 10% change from enrollment in percent of predicted Diffusing capacity of the Lungs for Carbon Monoxide (%) at 5 years
timeFrame: Baseline and 5 years
measure: Number of participants with more than 10% change from enrollment in percent of predicted Forced Vital Capacity (L) at 5 years
timeFrame: Baseline and 5 years
measure: Change from enrollment of calcium levels (mmol/L) at 5 years
timeFrame: Baseline and 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Karolinska University Hospital
name: Susanna M Kullberg, MD
role: PRINCIPAL_INVESTIGATOR
References: