Aging, Geriatric Syndromes and Clonal Hematopoiesis

Overview

In this study the investigators will incorporate a wide range of clinical variables associated with aging and cardiovascular disease to determine whether they are associated with mutation status independent of chronologic age. Clinically, aging can be operationalized using geriatric assessment, which entails a comprehensive multi-dimensional assessment of the health of an older adult, including measures of comorbidity, polypharmacy, functional status, cognition, depression, falls, social activities and social support. Given that aging is heterogeneous, geriatric assessment allows greater specificity for aging than chronological age alone.

Interventions

• Other Cognitive Assessment
  -Baseline and no more frequently than every 6 months until death
• Other Activities of Daily Living Questionnaire
  * 10 items about daily functional status * Baseline and no more frequently than every 6 months until death
• Other Instrumental Activities of Daily Living, subscale of the OARS
  * 7 items about daily functional status * Baseline and no more frequently than every 6 months until death
• Other Karnofsky Self-reported Performance Rating Scale
  * 1 item about daily functional status * Baseline and no more frequently than every 6 months until death
• Other Number of Falls
  * 1 item about daily functional status * Baseline and no more frequently than every 6 months until death
• Other Physical Health Section, subscale of the OARS
  * 13 items about comorbidity * Baseline and no more frequently than every 6 months until death
• Other MOS Social Activity Survey
  * 4 items about social activity * Baseline and no more frequently than every 6 months until death
• Other Unintentional Weight Loss
  * 2 items about nutrition * Baseline and no more frequently than every 6 months until death
• Genetic Peripheral Blood Draw
  -Baseline and no more frequently than every 6 months until death
• Genetic Buccal Swab
  * Participants will rinse their mouths 2 times with water for 20-30 seconds and discard the expectorated sample. One side of the inner cheek (buccal mucosa) will then be scraped with a cotton swab 20 times (alternatively, the tongue will be brushed 20 times with a toothbrush) * Baseline and no more frequently than every 6 months until death

Primary outcome measures

• Background mutation rate in hematopoietic stem cells from older adults regardless of a prior cancer diagnosis as measured by the number and frequency of hematopoietic-specific mutations [Time frame: Estimated to be 10 years]
• Presence or absence of geriatric syndromes as measured by hematopoietic stem cell mutations [Time frame: Estimated to be 10 years]
• Determine the natural history of mutations in older adults with clonal hematopoiesis as measured by risk to develop blood cancer/geriatric syndrome/illness/cardiovascular disease [Time frame: Estimated to be 10 years]
• Presence or absence of cardiovascular disease as measured by hematopoietic stem call mutations [Time frame: Estimated to be 10 years]
• Determine whether expansion of clonal hematopoiesis (CH) occurs following acute trauma [Time frame: Estimated to be 10 years]

Eligibility criteria

Inclusion criteria

• At least 50 years of age.
• Able to understand written and spoken English.
• Able to understand and willing to sign an IRB-approved written informed consent document (or that of a legally authorized representative, if applicable for the trauma cohort)

Exclusion criteria

• Inability or unwillingness to complete health questionnaire (with the exception of hip and knee replacement participants).
• History of a recent (<30 days) acute viral illness.
• Current cancer diagnosis and currently receiving chemotherapy or undergoing radiation therapy. A prior history of cancer is allowed if the participant completed therapy > 1 year prior to enrollment; participants with a prior diagnosis of cancer will be asked to sign a release of information for the research team to obtain records regarding their prior cancer treatment.
• Current use of drugs that cause DNA damage (e.g. Cytoxan, azathioprine, etc.) for the treatment of a non-malignant disease.
• Vulnerable populations (e.g. prisoners).
• Known infection with Hepatitis B or C, HTLV, or HIV.
• Additional exclusion for optional bone marrow aspirate/biopsy substudy:

• Use of medications for anticoagulation or "blood thinning" including warfarin, low molecular weight heparins (enoxaparin, daltaparin) or direct-acting oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban or betrixaban)
• allergy to lidocaine or other local anesthetics.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

United States · 1 center

• Washington University School of Medicine — St Louis

Identifiers

NCT: NCT02604563 · 201511019

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗