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

Not Applicable

Terminated

• Conditions: Sarcoidosis
• Interventions: Drug: all subjects will receive maraviroc 300mg orally twice a day for 6 weeks; Procedure: Bronchoscopy with bronchoalveolar lavage; Procedure: venipunctures; Procedure: Skin biopsy

• Registration Number: NCT02134717
• Lead Sponsor: Kevin F. Gibson

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.

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2014-04-30
• Study First Submitted QC: 2014-05-07
• Study First Posted: 2014-05-09
• Primary Completion: 2015-05
• Study Completion: 2015-05
• Results First Submitted: 2016-08-08
• Results First Submitted QC: 2017-06-20
• Results First Posted: 2017-07-18
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-17
• Last Update Posted: 2018-02-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
sarcoidosis stage II	all subjects will receive maraviroc 300mg orally twice a day for 6 weeks	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.
sarcoidosis stage II	Bronchoscopy with bronchoalveolar lavage	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.
sarcoidosis stage II	venipunctures	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.
sarcoidosis stage II	Skin biopsy	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.

Primary Outcome Measures

Name	Time	Method
Total Cell Count and Differentials in Blood and Bronchoalveolar Lavage Fluid Pre- and Post Maraviroc	6 weeks	General indicators of inflammation following chemokine receptor 5 (CCR5) inhibition in blood and bronchoalveolar lavage

Secondary Outcome Measures

Name	Time	Method
Mononuclear Cell (MNC) Activation and T-cell Differentiation	6 weeks	MNC activation and T-cell differentiation before and after CCR5 inhibition.
Chemokine Receptor 5 (CCR5) Expression Among These Immune Effector Cells	6 weeks	CCR5 expression among these immune effector cells before and after CCR5 inhibition.

Trial Locations

Locations (1)

Dorothy P. and Richard P. Simmons center for Interstitial lung Disease at the University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States