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
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Total Cell Count and Differentials in Blood and Bronchoalveolar Lavage Fluid Pre- and Post Maraviroc
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven sarcoidosis from any site (noncaseating granulomas without other causes).
- •Diagnosis of active sarcoidosis (Sec. 5.5.4.t) clinical stage II by Chest X-ray (CXR).
- •Forced Vital Capacity (FVC) >45% and Diffusing Capacity for Carbon Monoxide (DLCO) >50% of predicted values.
- •Evidence of active sarcoidosis (see criteria above)
- •Able and willing to complete all study procedures (e.g., bronchoscopy, post-drug surveillance)
- •Age: 18+ years old (prevalence greatest in young adults; pediatric maraviroc safety not established).
- •Not on immunosuppression for sarcoidosis at the time of recruitment, (e.g., steroids, tumor necrosis factor alpha (TNF-a) blockade)
- •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.
- •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).
- •Negative HIV and HBsAg tests
排除标准
- •Diagnosis of infection based upon clinical evaluation and/or microbial testing.
- •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.
- •Medications that will either inhibit or induce CYP3A4 (including St John's Wort)
研究组 & 干预措施
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.
干预措施: all subjects will receive maraviroc 300mg orally twice a day for 6 weeks (Drug)
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.
干预措施: Bronchoscopy with bronchoalveolar lavage (Procedure)
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.
干预措施: venipunctures (Procedure)
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.
干预措施: Skin biopsy (Procedure)
结局指标
主要结局
Total Cell Count and Differentials in Blood and Bronchoalveolar Lavage Fluid Pre- and Post Maraviroc
时间窗: 6 weeks
General indicators of inflammation following chemokine receptor 5 (CCR5) inhibition in blood and bronchoalveolar lavage
次要结局
- Mononuclear Cell (MNC) Activation and T-cell Differentiation(6 weeks)
- Chemokine Receptor 5 (CCR5) Expression Among These Immune Effector Cells(6 weeks)
研究者
Kevin F. Gibson
MD
University of Pittsburgh