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

Primary Purpose

Sarcoidosis

Status

Terminated

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

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

Bronchoscopy with bronchoalveolar lavage

venipunctures

Skin biopsy

About this trial

This is an interventional basic science trial for Sarcoidosis focused on measuring sarcoidosis, CCR5 inhibition, maraviroc

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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)

Sites / Locations

Dorothy P. and Richard P. Simmons center for Interstitial lung Disease at the University of Pittsburgh

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

sarcoidosis stage II

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Mononuclear Cell (MNC) Activation and T-cell Differentiation

MNC activation and T-cell differentiation before and after CCR5 inhibition.

Chemokine Receptor 5 (CCR5) Expression Among These Immune Effector Cells

CCR5 expression among these immune effector cells before and after CCR5 inhibition.

Full Information

NCT ID

NCT02134717

First Posted

April 30, 2014

Last Updated

January 17, 2018

Sponsor

Kevin F. Gibson

Collaborators

University of Pittsburgh

1. Study Identification

Unique Protocol Identification Number

NCT02134717

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2018

Overall Recruitment Status

Terminated

Why Stopped

Poor recruitment

Study Start Date

January 2014 (undefined)

Primary Completion Date

May 2015 (Actual)

Study Completion Date

May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Kevin F. Gibson

Collaborators

University of Pittsburgh

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sarcoidosis

Keywords

sarcoidosis, CCR5 inhibition, maraviroc

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

sarcoidosis stage II

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

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

Other Intervention Name(s)

maraviroc, selzentry

Intervention Type

Procedure

Intervention Name(s)

Bronchoscopy with bronchoalveolar lavage

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

venipunctures

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Skin biopsy

Intervention Description

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

Primary Outcome Measure Information:

Title

Total Cell Count and Differentials in Blood and Bronchoalveolar Lavage Fluid Pre- and Post Maraviroc

Description

General indicators of inflammation following chemokine receptor 5 (CCR5) inhibition in blood and bronchoalveolar lavage

Time Frame

6 weeks

Secondary Outcome Measure Information:

Title

Mononuclear Cell (MNC) Activation and T-cell Differentiation

Description

MNC activation and T-cell differentiation before and after CCR5 inhibition.

Time Frame

6 weeks

Title

Chemokine Receptor 5 (CCR5) Expression Among These Immune Effector Cells

Description

CCR5 expression among these immune effector cells before and after CCR5 inhibition.

Time Frame

6 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kevin F Gibson, MD

Organizational Affiliation

DorothyP. and Richard P. SImmons Center for Interstitial Lung Disease at the University of Pittsburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dorothy P. and Richard P. Simmons center for Interstitial lung Disease at the University of Pittsburgh

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

12. IPD Sharing Statement

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

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