Clonal Hematopoiesis of Indeterminate PotentialNCT04102423
CHIP/CCUS Natural History Protocol
An observational study of Clonal Hematopoiesis of Indeterminate Potential and Clonal Cytopenia of Undetermined Significance, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Clonal Hematopoiesis of Indeterminate Potential, Clonal Cytopenia of Undetermined Significance
- How many people
- 306 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Mar 2020to 15 Sep 2033
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Primary Clinical
Who may be able to join
- Greater than or equal to 18 years of age
- Willingness and capacity to provide written informed consent
- Presence of a somatic pathogenic variant associated with hematological malignancy
- Variant allele fraction of greater than or equal to 2% in at least one identified somatic pathogenic variant
- Greater than 18 years of age
- Willingness and capacity to provide written informed consent
Show all 13Show fewer
- Presence of a somatic pathogenic variant associated with hematological malignancy without morphological evidence of
- myelodysplasia and without a MDS defining cytogenetic abnormality
- Variant allele fraction of greater than or equal to 2% in at least one identified somatic pathogenic variant
- Bone marrow aspirate and biopsy excluding hematological malignancy and MDS
- Presence of a cytopenia for >30 days
- Hemoglobin, <10 g/dL; platelet count, <100 X10^9 /L; or absolute neutrophil count, <1.5 X10^9 /L
- At least 2 CBCs documented in a non-hospitalized patient at least 3 days apart
Who cannot join
- Known diagnosis of a hematological malignancy or bone marrow failure syndrome (excluding MGUS or MBL)
- Presence of a cytopenia:
- --Hemoglobin, <10 g/dL; platelet count, <100 X 10^9 /L; or absolute neutrophil count, <1.5 X 10^9 /L
- Pregnant at the time of recruitment
- Participants with Clonal Cytopenia of Uncertain Significance (CCUS):
- Known diagnosis of a hematological malignancy or bone marrow failure syndrome (excluding MGUS or MBL)
Show all 26Show fewer
- Morphological evidence of dysplasia on bone marrow aspirate / biopsy 10% dysplastic cells in any hematopoietic lineage
- Ringed sideroblasts >15%
- Presence of MDS defining cytogenetic abnormality
- Del(7q)
- del(5q)
- 17q or t(17p)
- Del(13q)
- del(11q)
- del(12p) or t(12p)
- del(9q)
- idic(X)(q13)
- t(11;16)
- t(3;21)
- t(1;3)
- t(2;11)
- inv(3)/t(3;3)
- 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.
- Alternate hematological diagnosis causing cytopenia
- Pregnant at time of recruitment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: Investigation of the Natural Progression of Clonal Hematopoiesis of Indeterminate Potential and Clonal Cytopenia of Undetermined Significance.
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.
Read more
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.
Read the detailed description
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).
- Conditions
- Clonal Hematopoiesis of Indeterminate Potential, Clonal Cytopenia of Undetermined Significance
- Keywords
- Cytopenia, Myelodysplastic Syndrome, Somatic Mutations, Natural History
- Medical subject headings
- Cytopenia, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| CCUS | All participants meeting the criteria for CCUS | |
| CHIP | Subjects will be split into five cohorts depending on specific mutations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Verify the previously studied association of myeloid somatic mutations with hematological malignancy
Association of myeloid somatic mutations with hematological malignancy
Measured: 10 years
Verify the previously studied association of myeloid somatic mutations with atherosclerosis
Association of myeloid somatic mutations with atherosclerosis
Measured: 10 years
Immune response
Assessing immune response by measuring markers of inflammation
Measured: 10 years
Examine potential new clinical associations
New clinical associations
Measured: 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
Measured: 10 years
Secondary outcomes (6)
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
Measured: 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
Measured: 10 years
Correlation between CHIP/CCUS and vitamin levels
To establish whether there is a correlation between CHIP/CCUS and vitamin levels
Measured: 10 years
Correlation between CHIP/CCUS and chronic renal impairment
To establish whether there is a correlation between CHIP/CCUS and chronic renal impairment
Measured: 10 years
Correlation between CHIP/CCUS and chronic lung disease
To establish whether there is a correlation between CHIP/CCUS and chronic lung disease
Measured: 10 years
Correlation between CHIP/CCUS and chronic liver disease
To establish whether there is a correlation between CHIP/CCUS and chronic liver disease
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2019
- Study start3 Mar 2020
- Primary completion15 Sep 2033 (estimated)
- Study completion15 Sep 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clonal Hematopoiesis of Indeterminate PotentialStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 306 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Fernanda Gutierrez Rodrigues, Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04102423
- Sponsor's protocol ID
- 190139
- Other IDs
- 19-H-0139
- Status last verified
- 24 Sep 2026
- First submitted
- 24 Sep 2019
- Last updated
- 28 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: It is not yet known.
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Natural Progression of Clonal Hematopoiesis of Indeterminate Potential and Clonal Cytopenia of Undetermined Significance.
- ClinicalTrials.gov ID
- NCT04102423
- Acronym / sponsor ID
- 190139
- Conditions
- Clonal Hematopoiesis of Indeterminate Potential, Clonal Cytopenia of Undetermined Significance
- Keywords
- Cytopenia, Myelodysplastic Syndrome, Somatic Mutations, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 306 participants (estimated)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 3 Mar 2020 (actual)
- Primary completion
- 15 Sep 2033 (estimated)
- Study completion
- 15 Sep 2033 (estimated)
- First posted
- 25 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CCUS | – | –All participants meeting the criteria for CCUS |
| CHIP | – | –Subjects will be split into five cohorts depending on specific mutations |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Primary Clinical
Key inclusion criteria (13 listed)
- Greater than or equal to 18 years of age
- Willingness and capacity to provide written informed consent
- Presence of a somatic pathogenic variant associated with hematological malignancy
- Variant allele fraction of greater than or equal to 2% in at least one identified somatic pathogenic variant
- Greater than 18 years of age
Key exclusion criteria (26 listed)
- Known diagnosis of a hematological malignancy or bone marrow failure syndrome (excluding MGUS or MBL)
- Presence of a cytopenia:
- --Hemoglobin, <10 g/dL; platelet count, <100 X 10^9 /L; or absolute neutrophil count, <1.5 X 10^9 /L
- Pregnant at the time of recruitment
- Known diagnosis of a hematological malignancy or bone marrow failure syndrome (excluding MGUS or MBL)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Verify the previously studied association of myeloid somatic mutations with hematological malignancy
Time frame: 10 years
Association of myeloid somatic mutations with hematological malignancy
Verify the previously studied association of myeloid somatic mutations with atherosclerosis
Time frame: 10 years
Association of myeloid somatic mutations with atherosclerosis
Immune response
Time frame: 10 years
Assessing immune response by measuring markers of inflammation
Examine potential new clinical associations
Time frame: 10 years
New clinical associations
Development of cytopenia, hematological malignancy, and the size and stability of leucocyte somatic mutations
Time frame: 10 years
Cytopenia, hematological malignancy, and the size and stability of leucocyte somatic mutations
6 secondary outcomes
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
Time frame: 10 years
Correlation between CHIP/CCUS and vitamin levels
Time frame: 10 years
Correlation between CHIP/CCUS and chronic renal impairment
Time frame: 10 years
Correlation between CHIP/CCUS and chronic lung disease
Time frame: 10 years
Correlation between CHIP/CCUS and chronic liver disease
Time frame: 10 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. It is not yet known.
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Heart Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Fernanda Gutierrez Rodrigues principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Clonal Hematopoiesis of Indeterminate Potential and Clonal Cytopenia of Undetermined Significance, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chanelle A Hutchinson ((301) 827-1094, chanelle.hutchinson@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Verify the previously studied association of myeloid somatic mutations with hematological malignancy (time frame: 10 years). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2026.