Impact of Chemokine Receptor 5 (CCR5) Inhibition on Sarcoidosis Immunophenotypes

NCT ID: NCT02134717

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2015-05-31

Brief Summary

The study hypothesizes that inhibition of the receptor CCR5 by maraviroc will diminish inflammation in patients with sarcoidosis. Subjects with active sarcoidosis will first undergo bronchoscopy with bronchoalveolar lavage to recover lung immune cells for baseline analysis. They will then receive the drug maraviroc for 6 weeks duration. They will then undergo a repeat bronchoscopy with bronchoalveolar lavage to recover lung immune cells for analysis following maraviroc treatment.

Detailed Description

The investigators hypothesize that inhibition of CCR5 by maraviroc may have a beneficial immunomodulatory effect on the granulomatous inflammation of pulmonary sarcoidosis. The specific aim of this proposal is the investigate the effect of CCR5 inhibition on the trafficking of mononuclear cells to the lung, skin, peripheral blood in subjects with active sarcoidosis exposed to the CCR5 inhibitor, maraviroc. A second aim will be to isolate by cell sorting cluster of differentiation 4 (CD4)+CCR5+ T cells for amplified gene expression profiling before and after CCR5 inhibition, experiments the investigators believe will elucidate genes associated with downstream activation and inhibition of CCR5 receptor function.

Conditions

Sarcoidosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

sarcoidosis stage II

All subjects with active stage II sarcoidosis with or without skin disease will receive the drug maraviroc 300mg to be taken orally twice a day for 6 weeks duration.

Group Type: EXPERIMENTAL

all subjects will receive maraviroc 300mg orally twice a day for 6 weeks

Intervention Type: DRUG

Bronchoscopy with bronchoalveolar lavage

Intervention Type: PROCEDURE

Bronchoscopy employs a flexible instrument that is inserted into the trachea and proximal airways after topical anesthesia. Bronchoalveolar lavage involves the instillation of saline solution through the bronchoscope into the airways followed by recovery under suction to collects lung fluid containing cells and proteins.

venipunctures

Intervention Type: PROCEDURE

Venipunctures will be performed at study entry, after two weeks, and at the end of the study to collect blood for research studies and safety laboratories.

Skin biopsy

Intervention Type: PROCEDURE

For subjects with sarcoidosis skin lesions, an optional skin biopsy specimen may be collected for research studies.

Interventions

all subjects will receive maraviroc 300mg orally twice a day for 6 weeks

Intervention Type: DRUG

Bronchoscopy with bronchoalveolar lavage

Bronchoscopy employs a flexible instrument that is inserted into the trachea and proximal airways after topical anesthesia. Bronchoalveolar lavage involves the instillation of saline solution through the bronchoscope into the airways followed by recovery under suction to collects lung fluid containing cells and proteins.

Intervention Type: PROCEDURE

venipunctures

Venipunctures will be performed at study entry, after two weeks, and at the end of the study to collect blood for research studies and safety laboratories.

Intervention Type: PROCEDURE

Skin biopsy

For subjects with sarcoidosis skin lesions, an optional skin biopsy specimen may be collected for research studies.

Intervention Type: PROCEDURE

Other Intervention Names

maraviroc; selzentry

Eligibility Criteria

Inclusion Criteria

1. Histologically proven sarcoidosis from any site (noncaseating granulomas without other causes).

2. Diagnosis of active sarcoidosis (Sec. 5.5.4.t) clinical stage II by Chest X-ray (CXR).

3. Forced Vital Capacity (FVC) >45% and Diffusing Capacity for Carbon Monoxide (DLCO) >50% of predicted values.

4. Evidence of active sarcoidosis (see criteria above)

5. Able and willing to complete all study procedures (e.g., bronchoscopy, post-drug surveillance)

6. Age: 18+ years old (prevalence greatest in young adults; pediatric maraviroc safety not established).

7. Not on immunosuppression for sarcoidosis at the time of recruitment, (e.g., steroids, tumor necrosis factor alpha (TNF-a) blockade)

8. Liver function (transaminases, bilirubin), coagulation (International Normalized Ratio (INR), partial thromboplastin time (PTT), platelet count), blood urea nitrogen (BUN), creatinine, and white blood count (WBC) within normal limits.

9. If female: negative pregnancy test, agreement to use reliable contraception if of childbearing potential 30 days prior and for 30 days after study completion (drug safety during pregnancy not established).

10. Negative HIV and HBsAg tests

Exclusion Criteria

1. Diagnosis of infection based upon clinical evaluation and/or microbial testing.

2. The diagnosis of any disease involving the heart, lungs, liver (HVC), kidney, hematologic, endocrine, or Gl systems which, in the judgment of the PI, would pose an undue risk to the subject if they participated in this study. This includes but is not limited to diabetes, uncontrolled hypertension, liver disease (HVC), or history of malignancy.

3. Medications that will either inhibit or induce CYP3A4 (including St John's Wort)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pittsburgh

OTHER

Sponsor Role: collaborator

Kevin F. Gibson

OTHER

Sponsor Role: lead

Responsible Party

Kevin F. Gibson

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kevin F Gibson, MD

Role: PRINCIPAL_INVESTIGATOR

DorothyP. and Richard P. SImmons Center for Interstitial Lung Disease at the University of Pittsburgh

Locations

Dorothy P. and Richard P. Simmons center for Interstitial lung Disease at the University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

U01HL112711

Identifier Type: NIH

Identifier Source: org_study_id

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