Recruiting

Observational Study

Sponsor:

National Heart, Lung, and Blood Institute (NHLBI)

Code:

NCT04102423

Conditions

Clonal Hematopoiesis of Indeterminate Potential

Clonal Cytopenia of Undetermined Significance

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Study Details

Brief 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. 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.

Conditions

Clonal Hematopoiesis of Indeterminate Potential

Clonal Cytopenia of Undetermined Significance

Study ID

NCT04102423

Start date

Mar 3, 2020

Status verified date

Aug 19, 2026

Completion date

Sep 15, 2033

Anticipated

Primary completion date

Sep 15, 2033

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

  • Participants with Clonal Hematopoiesis of Indeterminate Significance (CHIP):

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

  • 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

Study Design

Enrollment

306 participants

Anticipated

Interventions and Outcome Measures

Arms

CCUS

All participants meeting the criteria for CCUS

CHIP

Subjects will be split into five cohorts depending on specific mutations

Primary outcome measure

  • Verify the previously studied association of myeloid somatic mutations with hematological malignancy [ Time Frame: 10 years ]
  • Verify the previously studied association of myeloid somatic mutations with atherosclerosis [ Time Frame: 10 years ]
  • Immune response [ Time Frame: 10 years ]
  • Examine potential new clinical associations [ Time Frame: 10 years ]
  • Development of cytopenia, hematological malignancy, and the size and stability of leucocyte somatic mutations [ Time Frame: 10 years ]

Central Contacts and Locations

Central contacts

Chanelle A Hutchinson

(301) 827-1094chanelle.hutchinson@nih.gov

Emma M Groarke, M.D.

(301) 496-5093emma.groarke@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

800-411-1222ccopr@nih.gov

More Information

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Last update posted

Aug 21, 2026

Last verified

Aug 19, 2026

Keywords

  • Cytopenia
  • Myelodysplastic Syndrome
  • Somatic Mutations
  • Natural History

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Heart, Lung, and Blood Institute (NHLBI) on 2026-08-21.