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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

Tracking Information
First Submitted Date  ICMJE April 30, 2014
First Posted Date  ICMJE May 9, 2014
Results First Submitted Date  ICMJE August 8, 2016
Results First Posted Date  ICMJE July 18, 2017
Last Update Posted Date February 14, 2018
Study Start Date  ICMJE January 2014
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2017)
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
Original Primary Outcome Measures  ICMJE
 (submitted: May 7, 2014)
Total Cell Count and Differentials in Blood and Bronchoalveolar Lavage Fluid Pre- and Post Maraviroc [ Time Frame: 6 weeks ]
General indicators of inflammation following CCR5 inhibition in blood and bronchoalveolar lavage
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2018)
  • Mononuclear Cell (MNC) Activation and T-cell Differentiation [ Time Frame: 6 weeks ]
    MNC activation and T-cell differentiation before and after CCR5 inhibition.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2014)
  • Mononuclear cell activation and T-cell differentiation [ Time Frame: 6 weeks ]
    MNC activation and T-cell differentiation before and after CCR5 inhibition
  • CCRS expression among these immune effector cells [ Time Frame: 6 weeks ]
    CCRS expression among these immune effector cells before and after CCR5 inhibition
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Impact of Chemokine Receptor 5 (CCR5) Inhibition on Sarcoidosis Immunophenotypes
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Sarcoidosis
Intervention  ICMJE
  • 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.
Study Arms  ICMJE 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.
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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 6, 2016)
3
Original Estimated Enrollment  ICMJE
 (submitted: May 7, 2014)
10
Actual Study Completion Date  ICMJE May 2015
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02134717
Other Study ID Numbers  ICMJE U01HL112711( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kevin F. Gibson, University of Pittsburgh
Study Sponsor  ICMJE Kevin F. Gibson
Collaborators  ICMJE University of Pittsburgh
Investigators  ICMJE
Principal Investigator: Kevin F Gibson, MD DorothyP. and Richard P. SImmons Center for Interstitial Lung Disease at the University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP