CHIP/CCUS Natural History Protocol

NCT04102423 | Recruiting

• 2 other identifiers: 19013919-H-0139
• Study Type: observational
• Target: 306
• Locations: 1 country
• Sites: 1

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

Keywords

Cytopenia; Myelodysplastic Syndrome; Somatic Mutations; Natural History

Outcome Measures

Primary Outcomes (5)

• Verify the previously studied association of myeloid somatic mutations with hematological malignancy

  Association of myeloid somatic mutations with hematological malignancy

  10 years

• Verify the previously studied association of myeloid somatic mutations with atherosclerosis

  Association of myeloid somatic mutations with atherosclerosis

  10 years

• Immune response

  Assessing immune response by measuring markers of inflammation

  10 years

• Examine potential new clinical associations

  New clinical associations

  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

  10 years

Secondary Outcomes (6)

• Relationship between CHIP/CCUS and chronic viral infections such as CMV, EBV, HSV, HIV, Hepatitis B and Hepatitis C

  10 years

• Relationship between CHIP/CCUS and atherosclerosis, diabetes, and metabolic syndrome

  10 years

• Correlation between CHIP/CCUS and vitamin levels

  10 years

• Correlation between CHIP/CCUS and chronic renal impairment

  10 years

• Correlation between CHIP/CCUS and chronic lung disease

  10 years

Study Arms (2)

CCUS

All participants meeting the criteria for CCUS

CHIP

Subjects will be split into five cohorts depending on specific mutations

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Primary Clinical

You may qualify if:

• 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

You may not qualify if:

• 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):
• 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
• Known diagnosis of a hematological malignancy or bone marrow failure syndrome (excluding MGUS or MBL)

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Cytopenia; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Emma M Groarke, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tania R Machado

CONTACT

(301) 661-1505; tania.machado@nih.gov

Emma M Groarke, M.D.

CONTACT

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

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2019
• First Posted: September 25, 2019
• Study Start: March 3, 2020
• Primary Completion (Estimated): September 15, 2033
• Study Completion (Estimated): September 15, 2033
• Last Updated: March 17, 2026

Record last verified: 2026-03-13

Locations

US (1)