Clinical trial NCT05291468: the PHENOSAR Trial: Use of Antibiotics in Treatment of Sarcoidosis
Official title: PHENOtype Based Therapy With Antibiotics in SARcoidosis Patients With and Without Presence of Cutibacterium Acnes in Granulomatous Tissue
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sarcoidosis, Pulmonary
Sarcoidosis Skin
Keywords: Cutibacterium acnes
antibiotics
azithromycin
doxycycline
Lead sponsor: St. Antonius Hospital
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2022-03-22
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study population will be divided in 4 groups Group A consists of patients with C. Acnes present in their tissue Group B consists of patients without C. Acnes present in their tissue 50% of patients in each group will be treated with antibiotics and 50% with placebo.

Study duration is 4 months
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Biopsy proven sarcoidosis.
* No treatment indication for the sarcoidosis
* Inflammatory activity according to FDG-PET scan at baseline
* SUVmax above 3 in the lung and/or above 5 in mediastinum/hili

Exclusion Criteria:

* Increased duration of QT interval (\>440ms for men and \>450ms for women) on ECG
* Hearing deficits, as this is a possible side effect of azithromycin
* Being pregnant or breastfeeding at time of inclusion

Primary outcomes:
measure: SUVmax
timeFrame: 2 weeks
Secondary outcomes:
measure: lung function
timeFrame: 2 weeks
measure: quality of life according to questionnaire
timeFrame: 2 weeks
Other outcomes:
measure: serum biomarker: ACE
timeFrame: 2 weeks
measure: serum biomarker: IL-2R
timeFrame: 2 weeks
Locations:
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
state: Utrecht
Study officials:
References: