The PHENOSAR trial: Antibiotic treatment of biopsy confirmed phenotypes in sarcoidosis: a proof of concept clinical trial

Sarcoidosis is a multisystemic disease of unknown origin, characterized by the
formation of non-caseating granulomas. Sarcoidosis can be formed in every
organ, but most often the lungs and lymph nodes are affected. There is no
curative treatment for sarcoidosis, treatment is given to minimize risk of
organ failure and to suppress inflammation. The first-choice treatment for
sarcoidosis is prednisone, which is associated with numerous severe
side-effects. Also the second and third-choice medication for sarcoidosis are
associated with burdensome side effects. Recently, it was shown that the
intracellular signaling pathway mTOR plays a role in the pathogenesis of
sarcoidosis. Instead of inaccurate suppression of immune cells with
immunosuppressive, specific inhibition of this mTOR pathway showed to be
beneficial for some sarcoidosis patients. Inhibition of this pathway can be
done by antibiotics with immunomodulatory properties, such as azithromycin,
which comes with fewer side-effects compared to prednisone and methotrexate.
Furthermore, this antibiotic also has an inhibiting effect on a largely studied
trigger of sarcoidosis, the C. acnes bacterium. Already considerable research
has been done to the role of C. acnes in sarcoidosis pathogenesis and presence
of this bacterium has been associated with a more progressive disease.
Treatment of patients in whom C. acnes is present in and around the granuloma
may benefit from treatment with azithromycin, which may possibly also decrease
the possibility of a more progressive form later in life.

This study has been transitioned to CTIS with ID 2024-513534-38-00 check the CTIS register for the current data.

Investigate whether treatment with azithromycin has an inhibitory effect on the
mTOR pathway and/or C. acnes, causing a reduction of the inflammatory activity
which is found in sarcoidosis patients measured by blood biomarkers ACE and
sIL-2R and by FDG-PET/CT

Prospective cohort study.

The study population will be divided into two groups receiving either
Doxycycline and Azithromycin or placebo for 3 months. Both groups will contain
an equal amount of patient in which C. acnes can be detected in the tissue

Risk: Adverse effects of study treatment.
Burden:
FDGPET-scan: at start and end of study.
Blood tests: at start and end of study; 40 mL per occasion