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

Sarcoidosis Clinical Trial

— GRADS  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02134717
• Other study ID #: U01HL112711
• Status: Terminated
• Phase: N/A
• First received: April 30, 2014
• Last updated: January 17, 2018
• Start date: January 2014
• Est. completion date: May 2015

Study information

• Verified date: January 2018
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Sarcoidosis

Intervention

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

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

Locations

Country	Name	City	State
United States	Dorothy P. and Richard P. Simmons center for Interstitial lung Disease at the University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Kevin F. Gibson	University of Pittsburgh

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Cell Count and Differentials in Blood and Bronchoalveolar Lavage Fluid Pre- and Post Maraviroc	General indicators of inflammation following chemokine receptor 5 (CCR5) inhibition in blood and bronchoalveolar lavage	6 weeks
Secondary	Mononuclear Cell (MNC) Activation and T-cell Differentiation	MNC activation and T-cell differentiation before and after CCR5 inhibition.	6 weeks
Secondary	Chemokine Receptor 5 (CCR5) Expression Among These Immune Effector Cells	CCR5 expression among these immune effector cells before and after CCR5 inhibition.	6 weeks