Role of Interferon-gamma 1-b (IFN-γ) on Cells of the Innate Immune System: Functional, Biochemical and Gene Expression Studies in Patients With Chronic Granulomatous Disease

The overall goal of the study is to investigate the functional, biochemical, and gene expression effects of Interferon-gamma 1-b (IFN-γ) on the neutrophils of patients with Chronic Granulomatous Disease (CGD). The investigators hypothesize that the clinical effects demonstrated in patients with CGD treated with IFN-γ (decreased number and severity of infections) are the result of biochemical processes and upregulation of specific genes, which lead to enhanced functionality of this immune cell population.

Study Overview

• Status: Completed
• Conditions: Chronic Granulomatous Disease
• Intervention / Treatment: Drug: Interferon Gamma-1B

• Study Type: Observational
• Enrollment (Actual): 9

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 60 years (ADULT, CHILD)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The Investigators plan to enroll children and adults, aged 5-60 years with CGD defined by functional and biochemical or genetic testing. Enrollment will be stratified by the four main variants: X-linked, gp91phox deficient patients, and autosomal recessive CGD (p47phox deficient, p67phox deficient, and p22phox deficient patients).

Description

Inclusion Criteria:

• Current treatment with IFN-γ or intent to treat with this drug
• Acute infections resolved
• Subject is off treatment medications

• Women of childbearing potential must have:

  • a negative urine beta-HCG, and
  • be willing to practice two forms of effective contraception for the duration of study participation

Exclusion Criteria:

• Pregnancy,
• Breast-feeding, or
• Unwillingness to use effective contraception
• Recent vaccination (within the last fourteen days)
• Current infection or acute health condition requiring treatment

• Chronic inflammatory complications of CGD including:

  • gastric outlet or urinary tract obstruction,
  • pleuritis,
  • pericarditis,
  • inflammatory bowel disease, or
  • colitis requiring treatment.
• Un-associated chronic lung, liver, kidney, or cardiac disorders requiring active treatment

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Neutrophil bacterialcidal activity in patients with Chronic Granulomatous Disease (CGD) on standard treatment schedule and dose of IFN-γ in comparison to results for the patients off IFN-γ.	Determine changes in neutrophil function in neutrophils from patients with CGD	1 week off drug, 12 hours after a week of treatment
Changes in Gene expression as measured with RNA and affimetrics gene chips in patients with Chronic Granulomatous Disease (CGD) on standard treatment schedule and dose of IFN-γ in comparison to results for the patients off IFN-γ.	Determine changes in gene expression in neutrophils from patients with CGD.	1 week off drug, 12 hours after a week of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in Neutrophil biochemical studies in patients with Chronic Granulomatous Disease (CGD) on standard treatment schedule and dose of IFN-γ in comparison to results for the patients off IFN-γ.	Determine changes in biochemical tests in neutrophils from CGD patients.	1 week off drug, 12 hours after first dose of IFN-gamma; 12 hours after a week of treatment

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 16, 2018
• Primary Completion (ACTUAL): July 15, 2020
• Study Completion (ACTUAL): July 15, 2020

Study Registration Dates

• First Submitted: March 20, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (ACTUAL): June 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 20, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immunologic Deficiency Syndromes; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Leukocyte Disorders; Phagocyte Bactericidal Dysfunction; Granuloma; Granulomatous Disease, Chronic; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons; Interferon-gamma
• Other Study ID Numbers: 17-1676

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No