CHIP in Health and Disease

NCT07780552 | Not Yet Recruiting

• 1 other identifier: C_2_AB.8-0078
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Clonal hematopoiesis (CH), including clonal hematopoiesis of indeterminate potential (CHIP), is an age-associated condition characterized by the expansion of hematopoietic stem and progenitor cell clones carrying acquired somatic mutations. Although CH is associated with an increased risk of hematologic malignancies, its greater public health impact derives from its strong association with cardiovascular diseases, including coronary artery disease and stroke. Emerging evidence suggests that CH-associated mutations promote chronic inflammatory signaling in myeloid immune cells, thereby contributing to atherosclerosis and adverse cardiovascular remodeling. This observational translational study aims to characterize the biological spectrum of clonal hematopoiesis across different stages of disease risk and manifestation. Using state-of-the-art single-cell and multi-omics approaches, the study will compare inflammatory pathways, immune cell states, and mutation-associated molecular programs among healthy individuals without CH, individuals with high-risk CH, and patients with CH-associated hematologic or cardiovascular disease. The ultimate goal is to identify shared and disease-specific mechanisms linking clonal hematopoiesis to adverse clinical outcomes and to generate insights for future preventive, anti-clonal, and anti-inflammatory therapeutic strategies.

Conditions

Clonal Hematopoiesis; Clonal Hematopoiesis of Indeterminate Potential; Clonal Cytopenia of Undetermined Significance (CCUS); Myelodysplastic Syndrome; Cardiovascular Disease; Myocardial Infarction (MI); ST-elevation Myocardial Infarction (STEMI)

Keywords

Clonal Hematopoiesis; Clonal Hematopoiesis of Indeterminate Potential (CHIP); Somatic Mutations; DNMT3A; TET2; ASXL1; Inflammation; Myeloid Cells; Cardiovascular Disease; Atherosclerosis; Myocardial Infarction; STEMI; Clonal Cytopenia of Undetermined Significance (CCUS); Myelodysplastic Syndromes (MDS); Single-Cell RNA Sequencing; Multi-Omics; Immune Profiling; NLRP3 Inflammasome; cGAS-STING Pathway; Precision Medicine; Cardiovascular Risk; Healthy Aging; Chronic Inflammation; Biomarkers

Outcome Measures

Primary Outcomes (1)

• Inflammatory transcriptional profile of mutation-bearing immune cells

  Single-cell gene expression differences in predefined inflammatory pathways (including NLRP3 inflammasome, interferon signaling, and cGAS-STING-related pathways) between immune cells with and without clonal hematopoiesis-associated somatic variants and across study groups.

  Baseline

Study Arms (6)

Group A: Healthy Controls

Participants aged ≥60 years without detectable clonal hematopoiesis-associated somatic variants, no history of myocardial infarction or stroke, no cytopenia, no WHO-defined neoplasm, and no major surgery within the previous 3 months.

Group B: Low-Risk Clonal Hematopoiesis

Participants aged ≥60 years with clonal hematopoiesis carrying a somatic mutation in DNMT3A, TET2, ASXL1, or JAK2 (variant allele frequency ≥2%), no prior cardiovascular events, no cytopenia, no WHO-defined neoplasm, and a low Clonal Hematopoiesis Risk Score (CHRS \<9.5).

Group C: Intermediate-/High-Risk Clonal Hematopoiesis

Participants aged ≥60 years with clonal hematopoiesis carrying a somatic mutation in DNMT3A, TET2, ASXL1, or JAK2 (variant allele frequency ≥2%), no prior cardiovascular events, no cytopenia, no WHO-defined neoplasm, and an intermediate or high Clonal Hematopoiesis Risk Score (CHRS \>9.5).

Group D: Clonal Cytopenia of Undetermined Significance (CCUS)

Participants aged ≥60 years with clonal hematopoiesis-associated mutations and persistent unexplained cytopenia for at least 4 months who do not meet diagnostic criteria for a myeloid neoplasm based on bone marrow evaluation.

Group E: Cardiovascular Disease (Post-STEMI)

Participants aged ≥60 years with clonal hematopoiesis-associated mutations and a recent ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention within the previous 4 months, without prior stroke, coronary artery bypass graft surgery, cytopenia, or WHO-defined neoplasm.

Group F: Lower-Risk Myelodysplastic Syndrome (MDS)

Participants aged ≥60 years with newly diagnosed (\<3 months), untreated lower-risk myelodysplastic syndrome defined by an IPSS-R score \>1.5 to 3 points and no history of myocardial infarction or stroke.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults aged ≥60 years will be recruited across six predefined cohorts representing the continuum from healthy aging to clonal hematopoiesis-associated hematologic and cardiovascular disease. The study population includes healthy controls, individuals with low-risk and intermediate/high-risk clonal hematopoiesis, patients with clonal cytopenia of undetermined significance (CCUS), patients with low-risk myelodysplastic syndrome (MDS), and patients with recent ST-segment elevation myocardial infarction (STEMI).

You may qualify if:

• Written informed consent has been obtained for participation in the study "Deconvolution of Clonal Hematopoiesis-Associated Inflammation in Health and Disease"; OR
• Participant is enrolled in the Inn.Health study and has provided written informed consent; OR
• Participant is enrolled in the study "Clonal Hematopoiesis of Indeterminate Potential and Infarct Severity in ST-Elevation Myocardial Infarction" and has provided written informed consent.
• Group A: Control Group (n=20)
• Age ≥60 years
• No detectable somatic variant identified by peripheral blood next-generation sequencing (NGS)
• No history of stroke or myocardial infarction
• No surgery within the previous 3 months
• No diagnosis of a WHO-defined neoplasm
• No cytopenia at study enrollment Group B: Low-Risk Clonal Hematopoiesis Risk Score (CHRS) Group (n=20)
• Age ≥60 years
• Somatic variant in DNMT3A, TET2, ASXL1, or JAK2 with variant allele frequency (VAF) ≥2% in peripheral blood
• No history of stroke or myocardial infarction
• No surgery within the previous 3 months
• No diagnosis of a WHO-defined neoplasm

You may not qualify if:

• Treatment with immunosuppressive medication within the previous 4 weeks, including but not limited to systemic corticosteroids, methotrexate, other disease-modifying antirheumatic drugs (DMARDs), colchicine, TNF-α inhibitors, mTOR inhibitors, calcineurin inhibitors, or immunomodulatory antibodies
• History of rheumatologic, autoinflammatory, or autoimmune disease

Sponsors & Collaborators

• VASCage GmbH: lead
• Medical University Innsbruck: collaborator

Study Sites (1)

Medical University Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Biospecimen

Retention: SAMPLES WITH DNA

whole blood

MeSH Terms

Conditions

Myelodysplastic Syndromes; Cardiovascular Diseases; Myocardial Infarction; ST Elevation Myocardial Infarction; Inflammation; Atherosclerosis

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myocardial Ischemia; Heart Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Arteriosclerosis; Arterial Occlusive Diseases

Study Officials

• Dominik Wolf

  Medical University Innsbruck

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kai Zimmer

CONTACT

+43 512 504 83895; kai.zimmer@i-med.ac.at

Tina Pancheri

CONTACT

+4351255443513; tina.pancheri@vascage.at

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2026
• First Posted: August 21, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: August 21, 2026

Record last verified: 2026-08

Locations

AU (1)