the PHENOSAR Trial: Use of Antibiotics in Treatment of Sarcoidosis

February 10, 2026 updated by: Marcel Veltkamp, MD,PhD, St. Antonius Hospital

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Utrecht
      • Nieuwegein, Utrecht, Netherlands, 3435 CM
        • St. Antonius Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: C Acnes present in granulomatous tissue, treatment with antibiotics
patients who are in this arm will receive azithromycin and doxycycline for 3 months
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.
Other Names:
  • serum biomarkers
  • additional skin biopsy
Placebo Comparator: C Acnes present in granulomatous tissue, treatment with placebo
patients who are in this arm will receive placebo for 3 months
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.
Other Names:
  • serum biomarkers
  • additional skin biopsy
Active Comparator: C Acnes NOT present in granulomatous tissue, treatment with antibiotics
patients who are in this arm will receive azithromycin and doxycycline for 3 months
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.
Other Names:
  • serum biomarkers
  • additional skin biopsy
Placebo Comparator: C. Acnes NOT present in granulomatous tissue, treatment with placebo
patients who are in this arm will receive placebo for 3 months
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.
Other Names:
  • serum biomarkers
  • additional skin biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SUVmax
Time Frame: 2 weeks
Difference of standarized uptake value (SUVmax) uptake after treatment with antibiotics between patients with and without C. acnes in their granuloma
2 weeks

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
serum biomarker: ACE
Time Frame: 2 weeks
Determine whether treatment with azithromycin and doxycycline changes levels of serum biomarker Angiotensin Converting Enzyme (ACE) in U/I in sarcoidosis patients
2 weeks
serum biomarker: IL-2R
Time Frame: 2 weeks
Determine whether treatment with azithromycin and doxycycline changes levels of serum biomarker interleukin-2receptro (IL-2R) in pg/mL in sarcoidosis patients
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Antonius Hospital

Collaborators

ZonMw: The Netherlands Organisation for Health Research and Development

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2023

Primary Completion (Estimated)

April 26, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

February 25, 2022

First Submitted That Met QC Criteria

March 12, 2022

First Posted (Actual)

March 22, 2022

Study Record Updates

Last Update Posted (Actual)

February 12, 2026

Last Update Submitted That Met QC Criteria

February 10, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL73729.100.21

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

data of patients will be coded and will not be traceable to a specific participant when used by other researchers

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sarcoidosis, Pulmonary

Clinical Trials on FDG-PET/CT

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Trinidad & Tobago

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe