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

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ClinicalTrials.gov Identifier: NCT02134717
Recruitment Status : Terminated (Poor recruitment)
First Posted : May 9, 2014
Results First Posted : July 18, 2017
Last Update Posted : February 14, 2018
Sponsor:
Collaborator:
University of Pittsburgh
Information provided by (Responsible Party):
Kevin F. Gibson, University of Pittsburgh

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.

Condition or disease Intervention/treatment Phase
Sarcoidosis Drug: all subjects will receive maraviroc 300mg orally twice a day for 6 weeks Procedure: Bronchoscopy with bronchoalveolar lavage Procedure: venipunctures Procedure: Skin biopsy Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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 Start Date : January 2014
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sarcoidosis
Drug Information available for: Maraviroc

Arm Intervention/treatment
Experimental: 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.
Drug: all subjects will receive maraviroc 300mg orally twice a day for 6 weeks
Other Names:
  • maraviroc
  • selzentry

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.

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.

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




Primary Outcome Measures :
  1. Total Cell Count and Differentials in Blood and Bronchoalveolar Lavage Fluid Pre- and Post Maraviroc [ Time Frame: 6 weeks ]
    General indicators of inflammation following chemokine receptor 5 (CCR5) inhibition in blood and bronchoalveolar lavage


Secondary Outcome Measures :
  1. Mononuclear Cell (MNC) Activation and T-cell Differentiation [ Time Frame: 6 weeks ]
    MNC activation and T-cell differentiation before and after CCR5 inhibition.

  2. Chemokine Receptor 5 (CCR5) Expression Among These Immune Effector Cells [ Time Frame: 6 weeks ]
    CCR5 expression among these immune effector cells before and after CCR5 inhibition.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02134717


Locations
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United States, Pennsylvania
Dorothy P. and Richard P. Simmons center for Interstitial lung Disease at the University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Kevin F. Gibson
University of Pittsburgh
Investigators
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Principal Investigator: Kevin F Gibson, MD DorothyP. and Richard P. SImmons Center for Interstitial Lung Disease at the University of Pittsburgh
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Responsible Party: Kevin F. Gibson, MD, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02134717    
Other Study ID Numbers: U01HL112711 ( U.S. NIH Grant/Contract )
First Posted: May 9, 2014    Key Record Dates
Results First Posted: July 18, 2017
Last Update Posted: February 14, 2018
Last Verified: January 2018
Keywords provided by Kevin F. Gibson, University of Pittsburgh:
sarcoidosis
CCR5 inhibition
maraviroc
Additional relevant MeSH terms:
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Sarcoidosis
Lymphoproliferative Disorders
Lymphatic Diseases
Maraviroc
HIV Fusion Inhibitors
Viral Fusion Protein Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
CCR5 Receptor Antagonists