RECRUITING

NADPH Oxidase Correction in mRNA-transfected Granulocyte-enriched Cells in Chronic Granulomatous Disease (CGD)

Conditions

Chronic Granulomatous Disease Infection Primary Immune Deficiency systemic infection autologous transfusion Apheresis

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Background: CGD is caused by a gene mutation. For people with CGD, their cells cannot kill germs well, so they can get frequent or life-threatening infections. Researchers want to see if a new procedure can help a person s cells kill germs for a short time. It uses messenger RNA (mRNA) to deliver correct instructions for the gene mutation to the cells. Objective: To test a procedure in which mRNA is added to a person s blood cells. Eligibility: Males aged 18-75 with CGD with a mutation in the gene that makes the protein gp91phox. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Swab to test for strep throat Some screening tests will be repeated during the study. Participants will be admitted to the NIH Clinical Center hospital for at least 7 days. They will have apheresis. For this, a medicine is injected under their skin to prepare their white blood cells for collection. An IV line is placed into an arm vein. Blood goes through the IV line into a machine that divides whole blood into red blood cells, plasma, and white blood cells. The white blood cells are removed, and the rest of the blood is returned to the participant through an IV line in their other arm. The next day, they will get their mRNA-corrected cells via IV. They will be monitored for 3 more days. After discharge, participants will keep a symptom diary. They will be contacted weekly for one month, and then once a month. They will have a follow-up visit 3 months after the infusion.

Official Title

NADPH Oxidase Correction in mRNA Transfected Granulocyte-enriched Cells in Chronic Granulomatous Disease (CGD)

Quick Facts

Study Start:2022-07-22

Study Completion:2026-07-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05189925

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 75 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Males aged 18 to 75 years * CGD confirmed by DHR and deficiency subtype confirmed by protein analysis and/or genetic sequencing * Has a physician at home for follow-up care * Able to provide informed consent * For men who engage in activities that can result in pregnancy, agree to use contraception when engaging in sexual activities that can result in pregnancy. Contraception must be used from screening through 3 months after the CGD-Grans infusion. Acceptable methods of contraception include the following: * Hormonal contraception * Male or female condom	* Clinically unstable due to moderate to severe acute systemic infections as defined by persistent resting tachypnea, tachycardia, or hypoxia of \>20% from baseline and hypotension. * Current or history of stage 4 chronic kidney disease or estimated glomerular filtration rate \[eGFR\] \<30 mL/min/1.73 m\^2 within 90 days of baseline. * Unstable diabetes mellitus with hemoglobin A1c \>7.0% and fasting serum glucose \>200 mg/dL at screening. * Current or history of heart failure stage D as defined by the American College of Cardiology Foundation/American Heart Association guidelines. * History of arrhythmias that are symptomatic and deemed clinically unsafe for participation by NIH CC Cardiology consultation. * Current or history of invasive cancers that require chemotherapy within 5 years of screening. * Active hepatitis B, C, or HIV infections at screening. * Unstable hypertension requiring addition of new anti-hypertensives within 2 weeks of screening. * Impaired renal function that is unstable, with serum creatinine \>3.0 mg/dL and rising. * Serum transaminases and bilirubin that are \>3 x the upper limit of normal. * Electrocardiogram abnormalities indicative of acute myocardial injury, or arrhythmias that presents anesthetic risks, at screening. * Anemia with hemoglobin \<8 g/dL (transfusions to correct anemia permitted). * Thrombocytopenia (platelets \<50 x10\^9 cells/L) (platelet transfusions to correct thrombocytopenia permitted). * Profound thrombocytopenia (platelet counts \<10,000/microliter) that is not reversible with platelet transfusions. * Abnormal prothrombin time/partial thromboplastin time (PT/PTT) values outside the ranges accepted at the NIH CC that are not corrected or that cannot be attributed to presence of Lupus anticoagulant (commonly found in CGD patients). * Inherited bleeding disorder that precludes line placement. * Severe oxygen-dependent pulmonary disease that increases risks of procedures that may require sedation. * History of or current evidence of alcohol or illicit drug abuse or dependence. * Participation in a clinical protocol that includes an intervention that, in the opinion of the investigator, may affect the results of the current study.

Inclusion Criteria

Exclusion Criteria

* Males aged 18 to 75 years
* CGD confirmed by DHR and deficiency subtype confirmed by protein analysis and/or genetic sequencing
* Has a physician at home for follow-up care
* Able to provide informed consent
* For men who engage in activities that can result in pregnancy, agree to use contraception when engaging in sexual activities that can result in pregnancy. Contraception must be used from screening through 3 months after the CGD-Grans infusion. Acceptable methods of contraception include the following:
* Hormonal contraception
* Male or female condom

* Clinically unstable due to moderate to severe acute systemic infections as defined by persistent resting tachypnea, tachycardia, or hypoxia of \>20% from baseline and hypotension.
* Current or history of stage 4 chronic kidney disease or estimated glomerular filtration rate \[eGFR\] \<30 mL/min/1.73 m\^2 within 90 days of baseline.
* Unstable diabetes mellitus with hemoglobin A1c \>7.0% and fasting serum glucose \>200 mg/dL at screening.
* Current or history of heart failure stage D as defined by the American College of Cardiology Foundation/American Heart Association guidelines.
* History of arrhythmias that are symptomatic and deemed clinically unsafe for participation by NIH CC Cardiology consultation.
* Current or history of invasive cancers that require chemotherapy within 5 years of screening.
* Active hepatitis B, C, or HIV infections at screening.
* Unstable hypertension requiring addition of new anti-hypertensives within 2 weeks of screening.
* Impaired renal function that is unstable, with serum creatinine \>3.0 mg/dL and rising.
* Serum transaminases and bilirubin that are \>3 x the upper limit of normal.
* Electrocardiogram abnormalities indicative of acute myocardial injury, or arrhythmias that presents anesthetic risks, at screening.
* Anemia with hemoglobin \<8 g/dL (transfusions to correct anemia permitted).
* Thrombocytopenia (platelets \<50 x10\^9 cells/L) (platelet transfusions to correct thrombocytopenia permitted).
* Profound thrombocytopenia (platelet counts \<10,000/microliter) that is not reversible with platelet transfusions.
* Abnormal prothrombin time/partial thromboplastin time (PT/PTT) values outside the ranges accepted at the NIH CC that are not corrected or that cannot be attributed to presence of Lupus anticoagulant (commonly found in CGD patients).
* Inherited bleeding disorder that precludes line placement.
* Severe oxygen-dependent pulmonary disease that increases risks of procedures that may require sedation.
* History of or current evidence of alcohol or illicit drug abuse or dependence.
* Participation in a clinical protocol that includes an intervention that, in the opinion of the investigator, may affect the results of the current study.

Contacts and Locations

Study Contact

Joanna L Peterson

CONTACT

(301) 346-9780

joanna.peterson@nih.gov

Suk S De Ravin, M.D.

CONTACT

(301) 496-6772

sderavin@mail.nih.gov

Principal Investigator

Suk S De Ravin, M.D.

PRINCIPAL_INVESTIGATOR

National Institute of Allergy and Infectious Diseases (NIAID)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Suk S De Ravin, M.D., PRINCIPAL_INVESTIGATOR, National Institute of Allergy and Infectious Diseases (NIAID)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-07-22

Study Completion Date2026-07-01

Study Record Updates

Study Start Date2022-07-22

Study Completion Date2026-07-01

Terms related to this study

Keywords Provided by Researchers

Primary Immune Deficiency
systemic infection
autologous transfusion
Apheresis

Additional Relevant MeSH Terms

Chronic Granulomatous Disease
Infection