Clinical trial NCT02134717: Impact of Chemokine Receptor 5 (CCR5) Inhibition on Sarcoidosis Immunophenotypes
Official title: An Interventional Study of the Effect of CCR5 Inhibition With Maraviroc on Immune Cells in the the Lung and in Peripheral Blood of Patients With Sarcoidosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Sarcoidosis
Keywords: sarcoidosis
CCR5 inhibition
maraviroc
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh
First posted: 2014-05-09
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: Total Cell Count and Differentials in Blood and Bronchoalveolar Lavage Fluid Pre- and Post Maraviroc
timeFrame: 6 weeks
Secondary outcomes:
measure: Mononuclear Cell (MNC) Activation and T-cell Differentiation
timeFrame: 6 weeks
measure: Chemokine Receptor 5 (CCR5) Expression Among These Immune Effector Cells
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Dorothy P. and Richard P. Simmons center for Interstitial lung Disease at the University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: DorothyP. and Richard P. SImmons Center for Interstitial Lung Disease at the University of Pittsburgh
name: Kevin F Gibson, MD
role: PRINCIPAL_INVESTIGATOR
References: