the PHENOSAR Trial: Use of Antibiotics in Treatment of Sarcoidosis

NCT ID: NCT05291468

Last Updated: 2022-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-01

Study Completion Date

2023-06-30

Brief Summary

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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

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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.

Conditions

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Sarcoidosis, Pulmonary Sarcoidosis Skin

Keywords

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Cutibacterium acnes antibiotics azithromycin doxycycline

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 months
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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C Acnes present in granulomatous tissue, treatment with antibiotics

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

Group Type ACTIVE_COMPARATOR

FDG-PET/CT

Intervention Type RADIATION

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.

C Acnes present in granulomatous tissue, treatment with placebo

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

Group Type PLACEBO_COMPARATOR

FDG-PET/CT

Intervention Type RADIATION

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.

C Acnes NOT present in granulomatous tissue, treatment with antibiotics

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

Group Type ACTIVE_COMPARATOR

FDG-PET/CT

Intervention Type RADIATION

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.

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

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

Group Type PLACEBO_COMPARATOR

FDG-PET/CT

Intervention Type RADIATION

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.

Interventions

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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.

Intervention Type RADIATION

Other Intervention Names

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serum biomarkers additional skin biopsy

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role collaborator

St. Antonius Hospital

OTHER

Sponsor Role lead

Responsible Party

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Marcel Veltkamp, MD,PhD

Pulmonologist, Principle Investigator, member of staff ILD Center of Excllence

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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St. Antonius Hospital

Nieuwegein, Utrecht, Netherlands

Site Status

Countries

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Netherlands

Central Contacts

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Marcel Veltkamp, Dr.

Role: CONTACT

Phone: +31883201425

Email: [email protected]

Raisa Kraaijvanger, Msc.

Role: CONTACT

Phone: +31883201576

Email: [email protected]

Facility Contacts

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Marcel Veltkamp, Dr.

Role: primary

Raisa Kraaijvanger, MSc

Role: backup

Other Identifiers

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NL73729.100.21

Identifier Type: -

Identifier Source: org_study_id