An observational study in Granulomatous Disease, Chronic, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Status unknown at 44 sites in 2 countries. Per ClinicalTrials.gov, last updated 2021-09-02.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Observational
Chronic granulomatous disease (CGD) is an inherited immune system abnormality in which bone marrow transplantation (BMT) has been shown to be curative. However the risks of transplantation are high and not all patients with CGD may need to undergo this high risk procedure. This study will determine the long term medical condition and daily functioning of participants with CGD after a transplant and if possible, compare these results to participants who do not undergo a transplant.
Chronic granulomatous disease (CGD) is an immune deficiency where the neutrophils (a type of white blood cell that kills bacteria and fungi) do no work properly. Some individuals with CGD have neutrophils that do not work at all, whereas others have neutrophils that work partially, but not normally. In the past (over 20 years ago), most individuals with CGD were managed with antibiotics and antifungal medications alone. As the science of blood and marrow transplant (BMT) improved, some with CGD started to receive a BMT. It remained controversial whether individuals with CGD should receive a BMT or medical management alone (antibiotics, antifungals, and other treatments that do not include BMT).
The aim of this natural history study is to better define the role of BMT compared to medical management of CGD. Specifically, what are the outcomes of BMT versus medical management alone, why do some individuals with CGD benefit from BMT, and what are the long-term outcomes of both approaches. Researchers are interested in how individuals with CGD who have no neutrophil function may differ from those with some neutrophil function, how the types of infections and inflammatory complications of CGD impact on survival and how BMT may improve these complications. There are also questions as to how the types of bacteria (called the microbiome) found in the gastrointestinal tract (colon, large intestine) of individuals with CGD influences certain inflammatory complications (such as colitis), and how BMT changes the microbiome in individuals with CGD. All of this will help doctors in the future to better treat patients with CGD.
This study includes a retrospective (looking back into the past), cross-sectional (one time collection of information and/or research testing) and a prospective (looking from today and into the future) component. These are known as longitudinal studies (e.g., looking at information of participants over time).
Persons with CGD who were born 1988 to the present day are eligible, regardless of whether they received a BMT (as long as the BMT was after 1995) or medical therapy only. Individuals who are newly diagnosed with CGD can also be enrolled and followed longitudinally (over time), to determine their outcome from the choice of therapy that is made. An important component of this study is the 'cross sectional' study, where participants with more than 3 years of follow-up after transplant or diagnosis are asked to provide additional research blood work, and information is gathered regarding long-term transplant outcomes such as infections, graft-versus-host disease, autoimmune diseases, and quality of life. In addition, the participants will be asked to provide stool samples to allow investigators to look at how certain bacteria found in the gut (called the microbiome) affect complications of CGD, such as gastrointestinal disease. This will allow primary immune deficiency investigators/doctors to better understand the outcomes of different therapeutic approaches and to best design new treatments and clinical trials in the future for children with CGD.
79 studies on the registry are indexed under Granuloma; 8 are open to participants now.
This study's planned enrollment of 1,480 is above the median of 41 across 19 observational studies indexed under Granuloma.
Browse Granuloma studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,401 studies on the registry; 179 are open to participants now.
Of its 396 completed or terminated interventional studies of FDA-regulated products, 294 (74%) have results posted.
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Institutions participating in Rare Diseases Clinical Research Network (RDCRN)
Participant Inclusion Criteria (Part 1 - Longitudinal Analysis)
CGD Patients Undergoing Transplant 1995 to Present with Birth Year In or After 1988
CGD Patients will be Defined by both Defective Neutrophil NADPH Oxidase Function and by Clinical History Consistent with CGD
Patients must have both of:
A functional assay demonstrating abnormal NADPH oxidase function (see A below); AND Clinical history consistent with CGD (see B below).
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Patients must have both "A" and "B":
A. Function: Assays of NADPH Oxidase Function
I. Dihydrorhodamine (DHR) Assay:
II. Nitroblue Tetrazolium Oxidation Test (NBT):
o Diagnostic of CGD (reported as reduced granulocyte oxidative response). Report must be de-identified and provided. AND
B. Clinical History: One or More of the Following:
In cases where either functional assay (A) or history (B) is equivocal, one or more of the following may be used to confirm a diagnosis of CGD:
C. Absent or significantly reduced in expression or abnormal size of any of the 5 phox components (gp91 phox, p47 phox, p22 phox, p67phox, and p40phox) of NADPH oxidase, by either:
Molecular Diagnosis is Desirable In addition, molecular diagnosis (gene sequencing and expression analysis) of CGD is desirable and should be performed when possible.
Further Characterization of Oxidase Level, Longitudinal Study, Prospective Cohort Patients who are to undergo transplantation during the study period must be further characterized as oxidase-null or oxidase positive by level of oxidase production by either:
OR
o Genetic sequencing reporting a mutation that is unequivocally associated to absent oxidase production. (e.g. null mutations) will be classified as oxidase-null CGD (See discussion in Appendix I for how family history, genotype and CGD mutation information will be applied to assigning patients lacking any quantitative oxidase activity measurements to residual oxidase-null or residual oxidase-positive groups).
Exclusion Criteria:
Participant Exclusion Criteria (Longitudinal and Cross- Sectional Analyses)
Non-transplant subjects:
Longitudinal analysis
Longitudinal analysis
Cross-sectional analysis
Longitudinal analysis
Death
The event analyzed is death from any cause. The time from HCT to death or last follow up will be analyzed. Cause of death will also be collected. Surviving patients will be censored at the time of last observation.
Time frame: HCT to date of death, up to an expected average of 3 years
Engraftment
Engraftment will be measures in whole blood using either fluorescent in situ hybridization (FISH) for sex chromosomes or short tandem repeat polymerase chain reaction (PCR) or (STRs) in whole blood.
Time frame: an expected average of 3 years
Quality of Life Measures
Age appropriate testing will be performed at the cross-sectional visit in patients surviving at least two years posttransplant: * Pediatrics quality of life (QL) Family Impact Module, Parent Report * Peds QL Infant Scales Module (ages 1-24 months), Parent Report * Peds QL Generic Core Scales for Toddlers (ages 2-4 yr), Parent Report * Peds QL Generic Core Scales (ages 5-25 yr), Child/Parent Reports * Peds QL Transplant Module * Standard Form (SF)-36 (adult) * Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT BMT) (adult)
Time frame: an expected average of 3 years
Infections
CGD or transplant-related and transplant-related infection
Time frame: an expected average of 3 years
Autoimmune or inflammatory complications
- For HCT subjects, inflammation (inflammatory complications) includes chronic graft-versus-host disease (GVHD)
Time frame: an expected average of 3 years
This study is status unknown, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.
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National Institute of Allergy and Infectious Diseases (NIAID)