SNPMiner Trials by Shray Alag


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Report for Clinical Trial NCT02025829

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

The Role of IL-17 Neutrophils in CF Lung Inflammation

The purpose of this study is to determine whether IL-17 polymorphonuclear leukocytes (PMNs) are central to the disease pathology in CF. This will be determined by demonstrating that IL-17 PMNs are present in the CF airway, correlate with lung function measures, and decrease in patients being treated with IV antibiotics for a pulmonary exacerbation.

NCT02025829 Cystic Fibrosis
MeSH: Cystic Fibrosis Pneumonia Fibrosis Inflammation
HPO: Pneumonia


Primary Outcomes

Description: In the Exacerbation/IV Antibiotics Cohort--Subjects will serve as their own controls. The percentage of neutrophils (in sputum) positive for IL-17 was determined by flow cytometry for each subject at the beginning and end of treatment for a pulmonary exacerbation. Sputum IL-17 neutrophil counts will be compared to the change in lung function (FEV1) as determined by spirometry (American Thoracic Society standards).

Measure: Change in Sputum IL-17 Neutrophils

Time: End of Treatment, two weeks. Samples will be obtained from each study volunteer at the beginning of IV antibiotic treatment and at the completion of antibiotic treatment for a pulmonary exacerbation

Secondary Outcomes

Description: In the Clinically Stable Cohort--Measurement of sputum inflammatory mediators: IL-1β, IL-6, IL-8, IL-17A, TGF-β, TNF-α, and neutrophil elastase

Measure: Sputum Inflammatory Mediators: IL-1β, IL-6, IL-8, IL-17A, TGF-β, TNF-α, and Neutrophil Elastase

Time: Samples will be obtained at one outpatient clinic visit during the next calendar year

Description: In the Exacerbation/IV Antibiotics Cohort--Measurement of sputum inflammatory mediators by multiplex assay for IL-1β, IL-6, IL-8, and IL-17A. Neutrophil elastase determined by colorimetric assay. Measurements at the beginning of IV antibiotic treatment and after 2 weeks antibiotic treatment for a pulmonary exacerbation

Measure: Sputum Inflammatory Mediators: IL-1β, IL-6, IL-8, IL-17A, and Neutrophil Elastase

Time: End of Treatment, two weeks. Samples will be obtained from each study volunteer at the beginning of IV antibiotic treatment and at the completion of antibiotic treatment for a pulmonary exacerbation

Time Perspective: Prospective

Case-Only


There is one SNP

SNPs


1 G551D

Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Cystic Fibrosis Cystic Fibrosis Pneumonia Fibrosis Inflammation This study consists of two parts which will be conducted in parallel. --- G551D ---

Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Cystic Fibrosis Cystic Fibrosis Pneumonia Fibrosis Inflammation This study consists of two parts which will be conducted in parallel. --- G551D --- --- G551D ---

Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Cystic Fibrosis Cystic Fibrosis Pneumonia Fibrosis Inflammation This study consists of two parts which will be conducted in parallel. --- G551D --- --- G551D --- --- G551D ---

Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Inclusion Criteria: - For Both Cohorts: ≥ 18 < 50 years of age - For Both Cohorts: Must have a documented diagnosis of CF (positive sweat chloride ≥60 milliequivalents (mEq)/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype - For Both Cohorts: Chronically infected with P. aeruginosa defined by 2 positive cultures in the past year or 3 in the last two years - For Both Cohorts: Ability to expectorate mucus - For Both Cohorts: Ability to provide written informed consent - For Clinically Stable Cohort: 4 subjects with one copy of G551D - For Clinically Stable Cohort: 10 subjects who do not have G551D, they must have one copy of F508del - For Clinically Stable Cohort: CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) - For Clinically Stable Cohort: Clinically stable: free of any acute illness for >14 days - For Clinically Stable Cohort: Must have performed spirometry for clinical purposes at that clinical visit - For Clinically Stable Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes at the time of the study visit - For Clinically Stable Cohort: Have not been prescribed any new systemic antibiotics for the 14 days prior to enrollment - For Exacerbation/IV Antibiotics Cohort: One copy of F508del - For Exacerbation/IV Antibiotics Cohort: Must have a doctor defined pulmonary exacerbation requiring treatment with IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have performed spirometry for clinical purposes within 72 hours of initiating IV antibiotics and within 72 hours of completing IV antibiotics - For Exacerbation/IV Antibiotics Cohort: Must have a sputum culture sent to the clinical lab for clinical purposes within 72 hours of admission Exclusion Criteria: - For Both Cohorts: Pregnancy (based on self-report) - For Both Cohorts: Co-infection with Burkholderia cepacia complex organisms - For Both Cohorts: Any condition that in the opinion of the subject or the subject's managing physician that would compromise that individuals ability to participate in these studies - For Both Cohorts: Inability to tolerate the study procedures Cystic Fibrosis Cystic Fibrosis Pneumonia Fibrosis Inflammation This study consists of two parts which will be conducted in parallel. --- G551D --- --- G551D --- --- G551D --- --- G551D ---



HPO Nodes


HPO:
Pneumonia
Genes 208
TIMM8A DNAH9 GAS8 DNAH11 TNFRSF11A TBC1D24 SPAG1 MS4A1 GAS2L2 CCDC151 NIPBL BTK LIG4 NFKB2 TCIRG1 IGLL1 RNF168 STAT3 TAF1 RSPH4A CFTR NME8 DNAAF4 LEP CCDC65 NADK2 CD55 COL11A2 NHLRC1 PEPD CFAP300 LTBP3 WAS DNAI1 TBCD IL2RG GFI1 NBN RSPH1 CCDC39 PMM2 ICOS TNFSF12 IFNGR1 CARD11 SFTPC DNAL1 OFD1 ZMYND10 IL21R FMO3 SLC35A1 PLOD1 ORC6 RAG2 CACNA1C GAS8 RYR1 CFAP298 GNPTAB TNFRSF13B KDM6A PANK2 RANBP2 CYBA USB1 UBB DOCK8 ADA DNAAF2 KMT2D SAMD9 MUC5B IL7R DNAAF1 ICOS RAG2 CARD11 PTPRC ALMS1 NOTCH3 NSMCE3 DNAI1 TNFRSF13C GRHL3 EGFR IL2RG DNAAF6 PNP DNAH5 SETBP1 CR2 CD3E ADA MASP2 SFTPA2 ACTA1 RAC1 TTC25 FCGR2A ZAP70 SPEF2 IGHM DNAAF5 NBN CD247 DDR2 CD19 ACADVL KIAA0586 TK2 BLNK ARMC4 SGCG RAG1 CXCR4 NCF1 SRP54 FOXP3 IRF8 CFAP221 RNU4ATAC KCNJ6 LRBA CD3D P4HTM SELENON CCDC114 TNFRSF13B PLG DCLRE1C SLC25A24 DCLRE1C ICOS IL7R FOXJ1 JAK3 IL2RG CASP8 RAG1 OSTM1 CFAP410 CCNO NCF2 UNC119 TNFRSF13C JAK3 RNF125 STK36 POLA1 CD19 CR2 DNAH1 RSPH3 RSPH9 CYBB DRC1 DCLRE1C CCDC103 DNAAF3 LRRC56 PIGN LRRC6 SP110 PRKCD ACP5 CCDC40 SLC35C1 BTK MTHFD1 PGM3 RAG1 TERT CHD7 CFB TGFB1 RNU4ATAC SMARCD2 NKX2-1 OFD1 ZBTB24 BTK DNAI2 WDR19 ZAP70 CD79B CD81 COL11A2 NFIX RAG2 ELANE AFF4 NFKB1 IL2RG TNFRSF13C TNFSF12 CCDC114 ADA GBA DNAJB13 RPGR CSPP1 RMRP EPM2A DNMT3B NFKB2 MCIDAS HYDIN