In this study it is investigated whether treatment with azithromycin in combination with doxycycline reduces the bacterial load of C. acnes in granulomatous tissue of patients with sarcoidosis and subsequently decreases the inflammatory activation measured by FDG uptake and serum biomarkers.
Sarcoidosis is a multisystemic disease with unknown origin mostly affecting intrathoracic lymph nodes, lungs and skin. Sarcoidosis is characterized by the formation of non-caseating granulomas causing a variety of symptoms based on the organs involved. Although frequently described as a benign disease, mortality rate has been estimated to be around 11.0 per 1000 person-years in patients with sarcoidosis, with respiratory failure as the most common cause of death in the western world. The main treatment indication in sarcoidosis is risk of organ failure. In the literature the need for systemic treatment varies between 20-70%. Since there is no curative treatment for sarcoidosis, treatment is focused on suppression of the inflammation. This is usually done with the use of immunosuppressive drugs, such as prednisone and/or methotrexate, and in patients with severe refractory disease infliximab. It is well known that treatment with immunosuppressive drugs is associated with burdensome side effects for patients and impaired quality of life. Considerable research has been done on the possible role C. acnes in the pathogenesis of sarcoidosis. In a recent work of our own group it was shown that presence of C. acnes within granulomatous tissue can be detected in 41% of Dutch patients with sarcoidosis. Azithromycin has an inhibiting effect on several bacterial infections, such as C. acnes. Therefore, sarcoidosis patients with C. acnes in the granulomatous tissue might benefit from treatment with azithromycin. Given the fact that microbial resistance to azithromycin is relatively easy to develop, it is common practice to treat C. acnes with a combination of azithromycin and doxycycline.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
40
Patients will be randomized in a 1:1 ratio to either receive a combination of doxycycline and azithromycin or placebo during 3 months, after which the inflammatory state of disease is measured by FDG-PET/CT and serum biomarkers. If patients have cutaneous sarcoidosis, a skin biopsy will be performed at baseline and at the end of the study.
St. Antonius Hospital
Nieuwegein, Utrecht, Netherlands
SUVmax
Difference of standarized uptake value (SUVmax) uptake after treatment with antibiotics between patients with and without C. acnes in their granuloma
Time frame: 2 weeks
lung function
Difference in FVC after treatment with antibiotics between patients with and without C. acnes in their granulomatous tissue
Time frame: 2 weeks
quality of life according to questionnaire
Monitor quality of life for patients treated with antibiotics compared to patients receiving placebo, measured by King's Sarcoidosis Questionnaire that is taken at baseline and end of study. QOL is measured with the King's Sarcoidosis Questionnaire (KSQ), which is a validated questionnare on sarcoidosis with 5 scales and 29 items.
Time frame: 2 weeks
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