Effect of IFN-γ on Innate Immune Cells
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02609932|
Recruitment Status : Completed
First Posted : November 20, 2015
Last Update Posted : February 15, 2019
|Condition or disease||Intervention/treatment||Phase|
|Chronic Granulomatous Disease||Drug: Administration of drug (Interferon-gamma 1-b) subcutaneously||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Effect of Interferon-gamma 1-b on Innate Immune Cells|
|Study Start Date :||July 2016|
|Actual Primary Completion Date :||August 2018|
|Actual Study Completion Date :||February 2019|
SD or SS
In this study, IFN- γ-1b will be subcutaneously administered a total of 30 subjects in one of two cohorts; Single Dose (SD) or Steady State (SS) dosing. Dosing of IFN- γ-1b will be based upon the time subject became eligible and started study. In this non-randomized, open-label study, subjects will be enrolled on the SD cohort first, and once that cohort has been filled, enrollment to the SS cohort will begin. Although not required, subjects in the SD cohort may also volunteer to participate in the SS cohort if they still meet eligibility criteria. Separate consents will be used for the SD and SS cohorts. In the event not all the SD subjects choose to continue onto the SS cohort, we will plan to recruit new participants from our local campus community.
Drug: Administration of drug (Interferon-gamma 1-b) subcutaneously
SD = group who has received a single dose of IFN-gamma (10, 25, 50, and 100 mcg/m2) given once with subsequent analysis of effects (serum IL-10, Neuropterin, and IFN levels as well as neutrophil Nox2 activity and gene expression by Affimetrics Chip analysis). One month is allowed between doses. SS = administration of four doses (50 mcg/m2) of IFN-gamma given on Monday, Wednesday Friday schedule with neutrophil or monocyte function studies performed before the first and after the fourth dose to determine steady state effects.
Other Name: Actimmune
- Change in Neutrophil Nox2 activity. [ Time Frame: Determine the change in Nox2 activity at baseline compared to results for 8,24,48,72,96 hours after each IFN dose for the SD cohort. ]Nox2 activity will be measured by DHR oxidation or Sod inhibitable cytochrome c reduction.
- Change in Plasma IL-10 and Neuropterin concentration. [ Time Frame: Determine the change in IL-10 and neuropterin concentration at baseline compared to 4, 8, 12, 24, 36, 48, 72, and 96 hours after each IFN dose, SD cohort. ]IL-10nd Neuropterin will be measured by ELISA.
- Change in Neutrophil Gene Expression Analysis. [ Time Frame: Determine the change in gene expression at baseline compared to 4, 8, 12, 24, 36, 48, 72, and 96 hours after each IFN dose, SD cohort. ]RNA will be extracted and gene expression will be determined by Affimetrix Gene Chip assay.
- Change in IFN concentration and detection of anti-IFN antibody [ Time Frame: Determine the change in IFN level at baseline compared to 4, 8, 12, and 24 hours after administration of each dose of IFN-gamma in the SD cohort. Determine the change in IFN antibody at baseline compared to day 7-10 and day 30 after IFN ]IFN levels and anti-drug antibody will be completed by standard assays.
- Change in Neutrophil Function studies. [ Time Frame: Determine the change in neutrophil function at baseline compared to results on Day 8 after the 4th dose of IFN. ]Neutrophil chemotaxis, bactericidal activity,ingestion, degranulation, f-Actin expression, CD11b/18 expression, Nox2 activity to a variety of agonists.
- Change in Anti-IFN antibody. [ Time Frame: Determine the change in IFN antibody at baseline compared to results for 7-10 da. and 30 da. after IFN. ]Anti-drug antibody to be determined by standard assay.
- Change in Monocyte function studies. [ Time Frame: Determine the change in monocyte function at baseline compared to results on Day 8 after the 4th dose of IFN. ]Monocyte chemotaxis, bactericidal activity,ingestion, Expression of monocyte specific surface determinants, CD11b/18 expression, Nox2 activity to a variety of agonists, cell content of specific proteins, and antibody dependent cellular cytotoxicity.
- Change in Neutrophil and Monocyte Gene Expression Analysis. [ Time Frame: Determine the change in monocyte function at baseline compared to results on Day 8 after the 4th dose of IFN. ]RNA will be extracted and gene expression will be determined by Affimetrix Gene Chip assay.
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): NCT02609932
|United States, Colorado|
|University of Colorado Denver, Anschutz Medical Campus|
|Aurora, Colorado, United States, 80045|
|Principal Investigator:||Daniel R. Ambruso, MD||University of Colorado, Denver|