the PHENOSAR Trial: Use of Antibiotics in Treatment of Sarcoidosis

Sarcoidosis, Pulmonary Clinical Trial

Official title:

PHENOtype Based Therapy With Antibiotics in SARcoidosis Patients With and Without Presence of Cutibacterium Acnes in Granulomatous Tissue

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05291468
• Other study ID #: NL73729.100.21
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 1, 2023
• Est. completion date: June 30, 2023

Study information

• Verified date: December 2022
• Source: St. Antonius Hospital
• Contact: Marcel Veltkamp, Dr.
• Phone: +31883201425
• Email: m.veltkamp[@]antoniusziekenhuis.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: June 30, 2023
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sarcoidosis
• Sarcoidosis, Pulmonary

Intervention

Radiation:
• FDG-PET/CT
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.

Locations

Country	Name	City	State
Netherlands	St. Antonius Hospital	Nieuwegein	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
St. Antonius Hospital	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	serum biomarker: ACE	Determine whether treatment with azithromycin and doxycycline changes levels of serum biomarker Angiotensin Converting Enzyme (ACE) in U/I in sarcoidosis patients	2 weeks
Other	serum biomarker: IL-2R	Determine whether treatment with azithromycin and doxycycline changes levels of serum biomarker interleukin-2receptro (IL-2R) in pg/mL in sarcoidosis patients	2 weeks
Primary	SUVmax	Difference of standarized uptake value (SUVmax) uptake after treatment with antibiotics between patients with and without C. acnes in their granuloma	2 weeks
Secondary	lung function	Difference in FVC after treatment with antibiotics between patients with and without C. acnes in their granulomatous tissue	2 weeks
Secondary	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.	2 weeks