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

Kevin F. Gibson

Status: Terminated

Conditions: Sarcoidosis

Treatments: Procedure: Bronchoscopy with bronchoalveolar lavage; Drug: all subjects will receive maraviroc 300mg orally twice a day for 6 weeks; Procedure: venipunctures; Procedure: Skin biopsy

Study type: Interventional

Funder types: Other

Identifiers

NCT02134717

U01HL112711

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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3 participants in 1 patient group

sarcoidosis stage II

Experimental group

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.

Treatment:

Procedure: Skin biopsy

Procedure: venipunctures

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

Procedure: Bronchoscopy with bronchoalveolar lavage