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

NCT03548818 | Completed DMC FDA Drug

• 1 other identifier: 17-1676
• Study Type: observational
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Granulomatous Disease

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• 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.

  1 week off drug, 12 hours after first dose of IFN-gamma; 12 hours after a week of treatment

Interventions

Interferon Gamma-1B DRUG

Study function and biochemistry of neutrophils off the drug for one week and then 12 hours after first dose and fourth dose.

Also known as: None Noted

Eligibility Criteria

• Age: 5 Years - 60 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• 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).

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Ambruso DR, Briones NJ, Tran AD, Sanford B, Childs C, Katz BZ, Ellison M, Johnston RB, Jones KL. Interferon-gamma 1b-induced gene expression alters neutrophil function in patients with chronic granulomatous disease. PLoS One. 2025 Sep 8;20(9):e0331657. doi: 10.1371/journal.pone.0331657. eCollection 2025.

  PMID: 40920799 DERIVED

MeSH Terms

Conditions

Granulomatous Disease, Chronic

Interventions

interferon gamma-1b

Condition Hierarchy (Ancestors)

Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Daniel R. Ambruso, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2018
• First Posted: June 7, 2018
• Study Start: May 16, 2018
• Primary Completion: July 15, 2020
• Study Completion: July 15, 2020
• Last Updated: January 22, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)