the PHENOSAR Trial: Use of Antibiotics in Treatment of Sarcoidosis

Not Applicable

Not yet recruiting

• Conditions: Sarcoidosis Skin; Sarcoidosis, Pulmonary
• Interventions: Radiation: FDG-PET/CT

• Registration Number: NCT05291468
• Lead Sponsor: St. Antonius Hospital

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.

Study Timeline

• Study First Submitted: 2022-02-25
• Study First Submitted QC: 2022-03-12
• Study First Posted: 2022-03-22
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-11
• Last Update Posted: 2022-12-13
• Study Start: 2023-01-01
• Primary Completion: 2023-04-30
• Study Completion: 2023-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
C Acnes present in granulomatous tissue, treatment with antibiotics	FDG-PET/CT	patients who are in this arm will receive azithromycin and doxycycline for 3 months
C Acnes NOT present in granulomatous tissue, treatment with antibiotics	FDG-PET/CT	patients who are in this arm will receive azithromycin and doxycycline for 3 months
C. Acnes NOT present in granulomatous tissue, treatment with placebo	FDG-PET/CT	patients who are in this arm will receive placebo for 3 months
C Acnes present in granulomatous tissue, treatment with placebo	FDG-PET/CT	patients who are in this arm will receive placebo for 3 months

Primary Outcome Measures

Name	Time	Method
SUVmax	2 weeks	Difference of standarized uptake value (SUVmax) uptake after treatment with antibiotics between patients with and without C. acnes in their granuloma

Secondary Outcome Measures

Name	Time	Method
lung function	2 weeks	Difference in FVC after treatment with antibiotics between patients with and without C. acnes in their granulomatous tissue
quality of life according to questionnaire	2 weeks	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.

Trial Locations

Locations (1)

St. Antonius Hospital; 🇳🇱 Nieuwegein, Utrecht, Netherlands