the PHENOSAR Trial: Use of Antibiotics in Treatment of Sarcoidosis

St. Antonius Hospital

Status: Not yet enrolling

Conditions: Sarcoidosis Skin; Sarcoidosis, Pulmonary

Treatments: Radiation: FDG-PET/CT

Study type: Interventional

Funder types: Other

Identifiers

NCT05291468

NL73729.100.21

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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40 participants in 4 patient groups, including a placebo group

C Acnes present in granulomatous tissue, treatment with antibiotics

Active Comparator group

Description:

patients who are in this arm will receive azithromycin and doxycycline for 3 months

Treatment:

Radiation: FDG-PET/CT

C Acnes present in granulomatous tissue, treatment with placebo

Placebo Comparator group

Description:

patients who are in this arm will receive placebo for 3 months

Treatment:

Radiation: FDG-PET/CT

C Acnes NOT present in granulomatous tissue, treatment with antibiotics

Active Comparator group

Description:

patients who are in this arm will receive azithromycin and doxycycline for 3 months

Treatment:

Radiation: FDG-PET/CT

C. Acnes NOT present in granulomatous tissue, treatment with placebo

Placebo Comparator group

Description:

patients who are in this arm will receive placebo for 3 months

Treatment:

Radiation: FDG-PET/CT