the PHENOSAR Trial: Use of Antibiotics in Treatment of Sarcoidosis

Sponsor

St. Antonius Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05291468

Collaborator

ZonMw: The Netherlands Organisation for Health Research and Development (Other)

Enrollment

Location

Arms

14.9

Anticipated Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sarcoidosis, Pulmonary Sarcoidosis Skin	Radiation: FDG-PET/CT	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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 monthsThe 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

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Apr 1, 2022

Anticipated Primary Completion Date :

Apr 30, 2023

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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.

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Antonius Hospital	Nieuwegein	Utrecht	Netherlands	3435 CM

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Marcel Veltkamp, MD,PhD, Pulmonologist, Principle Investigator, member of staff ILD Center of Excllence, St. Antonius Hospital

ClinicalTrials.gov Identifier:

NCT05291468

Other Study ID Numbers:

NL73729.100.21

First Posted:

Mar 22, 2022

Last Update Posted:

Apr 8, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Marcel Veltkamp, MD,PhD, Pulmonologist, Principle Investigator, member of staff ILD Center of Excllence, St. Antonius Hospital

Additional relevant MeSH terms:

Sarcoidosis, Pulmonary

Sarcoidosis

Study Results

No Results Posted as of Apr 8, 2022