An observational study in Clonal Hematopoiesis of Indeterminate Potential and Clonal Cytopenia of Undetermined Significance, sponsored by National Heart, Lung, and Blood Institute (NHLBI). Recruiting at 1 site in United States. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by National Heart, Lung, and Blood Institute (NHLBI) · Observational
Background:
Clonal Hematopoiesis of Indeterminate Potential (CHIP) is a change in a person s DNA that can increase a person s risk of developing blood cancers or cardiovascular disease. CHIP occurs mostly occurs in older people. Clonal cytopenia of undetermined significance (CCUS) occurs when one or more blood cell types is lower than it should be and is associated with a change in their DNA. Researchers want to learn more about how CHIP and CCUS progress.
Objective:
To examine the natural history of people in a study of CHIP and CCUS to (1) verify the association of myeloid somatic mutations with atherosclerosis and blood cancers, and (2) find new potential clinical associations.
Eligibility:
Adults 18 and older with CHIP with a somatic pathogenic variant associated with blood cancers. Adults with CCUS are also needed.
Design:
Potential participants will be screened with gene testing. For this, they will give a blood sample. They will also be enrolled in NHLBI screening protocol #97-H-0041. Those who pass this screening will visit the NIH Clinical Center for more screening tests. For this, they will give a blood sample. They will have a physical exam. They will give their medical history. They may give a urine sample. Those with CCUS will have bone marrow taken.
Eligible participants will give blood and urine samples. Their heart activity will be monitored and tested. The arteries in their neck will be assessed using ultrasound. They will have liver and heart scans. They will have a bone mineral density scan. They will have lung function tests. They will have the inside of their cheek swabbed or have a skin punch biopsy. They will have the option to have advanced scans done of their heart and full body but this is not required.
Participants will have yearly follow-up visits for 10 years. They will repeat the above procedures every 1-3 years depending on the procedure.
Clonal Hematopoiesis of Indeterminate Potential (CHIP) has been defined as the presence of a somatic pathogenic variant associated with hematological malignancy, with an allele fraction of at least 2%, without morphological evidence of bone marrow dysplasia or neoplasia. Such variants are small, occur in leukocytes and are found in a substantial proportion of the healthy aging population using next generation sequencing (NGS). They are thought to represent a pre-neoplastic phase of hematological malignancy, particularly myeloid disorders such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). They are considered by some to be analogous to monoclonal B cell lymphocytosis (MBL), or monoclonal gammopathy of uncertain significance (MGUS) as precursors for chronic lymphocytic leukemia (CLL) and myeloma respectively, and, with a similar rate of progression of 0.5%-1% per year.
CHIP is strongly associated with advancing age with a prevalence of up to 10% in those >65 years of age compared to 1% in those \<50 years of age, and has also been associated with an increased atherosclerotic risk, and an increase in overall mortality. Despite this association, most people with CHIP are denoted healthy and do not progress to hematological malignancy. Those with low blood counts in association with a - termed clonal cytopenias of undetermined significance (CCUS) - do show a significantly higher rate of progression to myeloid malignancy, more analogous to patients with low risk MDS, though they are currently not classified as such as they lack the morphological dysplasia or defining chromosomal abnormalities.
The optimal follow-up and management of CHIP and CCUS is not yet established - evidence has suggested that factors such as which specific variant, how many variants are present, and the frequency at which these variants increase can help us to delineate high and low risk status. Some recent data has shown that the presence of CHIP is associated with increased levels of inflammation. In depth, investigation should provide further insight into the pathogenesis and progression of this process. The establishment of a natural history protocol will allow patients with CHIP and CCUS to be followed prospectively in a clinical setting. This protocol will have many collaborators from different institutes providing expertise including National Human Genome Research Institute (NHGRI), National Heart, Lung and Blood Institute (NHLBI), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the Department of Laboratory Medicine (DLM).
81 studies on the registry are indexed under Cytopenia; 25 are open to participants now.
This study's planned enrollment of 306 is above the median of 202 across 15 observational studies indexed under Cytopenia.
Browse Cytopenia studies →National Heart, Lung, and Blood Institute (NHLBI) is the lead sponsor of 1,143 studies on the registry; 71 are open to participants now.
Of its 58 completed or terminated interventional studies of FDA-regulated products, 51 (88%) have results posted.
Counted across the registry records on this site, refreshed daily.
Primary Clinical
INCLUSION CRITERIA:
EXCLUSION CRITERIA:
Presence of a cytopenia:
--, \<10 g/dL; count, \<100 X 10\^9 /L; or , \<1.5 X 10\^9 /L
Participants with Clonal Cytopenia of Uncertain Significance (CCUS):
INCLUSION CRITERIA:
myelodysplasia and without a MDS defining cytogenetic abnormality
Presence of a cytopenia for >30 days
EXCLUSION CRITERIA:
Presence of MDS defining cytogenetic abnormality
t(6;9)
--Note: As a sole cytogenetic abnormality in the absence of morphological criteria, gain of chromosome 8, del(20q) and loss of chromosome Y are not considered definitive evidence of MDS.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All participants meeting the criteria for CCUS
Subjects will be split into five cohorts depending on specific mutations
Verify the previously studied association of myeloid somatic mutations with hematological malignancy
Association of myeloid somatic mutations with hematological malignancy
Time frame: 10 years
Verify the previously studied association of myeloid somatic mutations with atherosclerosis
Association of myeloid somatic mutations with atherosclerosis
Time frame: 10 years
Immune response
Assessing immune response by measuring markers of inflammation
Time frame: 10 years
Examine potential new clinical associations
New clinical associations
Time frame: 10 years
Development of cytopenia, hematological malignancy, and the size and stability of leucocyte somatic mutations
Cytopenia, hematological malignancy, and the size and stability of leucocyte somatic mutations
Time frame: 10 years
Relationship between CHIP/CCUS and chronic viral infections such as CMV, EBV, HSV, HIV, Hepatitis B and Hepatitis C
To establish whether there is a relationship between CHIP/CCUS and chronic viral infections such as CMV, EBV, HSV, HIV, Hepatitis B and Hepatitis C
Time frame: 10 years
Relationship between CHIP/CCUS and atherosclerosis, diabetes, and metabolic syndrome
To establish whether there is a relationship between CHIP/CCUS and atherosclerosis, diabetes, and metabolic syndrome
Time frame: 10 years
Correlation between CHIP/CCUS and vitamin levels
To establish whether there is a correlation between CHIP/CCUS and vitamin levels
Time frame: 10 years
Correlation between CHIP/CCUS and chronic renal impairment
To establish whether there is a correlation between CHIP/CCUS and chronic renal impairment
Time frame: 10 years
Correlation between CHIP/CCUS and chronic lung disease
To establish whether there is a correlation between CHIP/CCUS and chronic lung disease
Time frame: 10 years
Correlation between CHIP/CCUS and chronic liver disease
To establish whether there is a correlation between CHIP/CCUS and chronic liver disease
Time frame: 10 years
Plan to share: Undecided — It is not yet known.
Started Mar 2020 (actual). Primary completion is estimated for Sep 2033, 162 months after the start.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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