NCT04102423 · National Heart, Lung, and Blood Institute (NHLBI)
CHIP/CCUS Natural History Protocol
What this study is about
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.
View original scientific description
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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
Exclusion criteria
- 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): INCLUSION CRITERIA:
- Greater than 18 years of age
- Willingness and capacity to provide written informed consent
- 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 EXCLUSION CRITERIA:
- Known diagnosis of a hematological malignancy or bone marrow failure syndrome (excluding MGUS or MBL)
- 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
- 17q or t(17p)
- del(12p) or t(12p)
- idic(X)(q13)
- 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
Where
- Bethesda, Maryland
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 18, 2026 · Source of record for eligibility and locations