Aging, Geriatric Syndromes and Clonal Hematopoiesis

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.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Aged; Geriatrics; Geriatric Syndromes
• Intervention / Treatment: Other: Cognitive Assessment; Other: Activities of Daily Living Questionnaire; Other: Instrumental Activities of Daily Living, subscale of the OARS; Other: Karnofsky Self-reported Performance Rating Scale; Other: Number of Falls; Other: Physical Health Section, subscale of the OARS; Other: MOS Social Activity Survey; Other: Unintentional Weight Loss; Genetic: Peripheral Blood Draw; Genetic: Buccal Swab; Other: Heart Health and Smoking History from BRFSS questionnaire; Other: Gait Speed; Other: Grip Strength; Other: Height and Weight measurements; Other: Blood pressure measurement; Procedure: Optional bone marrow biopsy; Procedure: Blood draw for trauma measurements

• Study Type: Observational
• Enrollment (Estimated): 2000

Contacts and Locations

• Study Contact: Name: Meagan Jacoby, M.D.; Phone Number: 314-747-8439; Email: mjacoby@wustl.edu
• Study Contact Backup: Name: Kristina Williams, B.S.; Phone Number: 314-362-6963; Email: kjw1@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: Meagan Jacoby, M.D.; Phone Number: 314-747-8439; Email: mjacoby@wustl.edu
      • Contact: Kristi Williams, B.S.; Phone Number: 314-362-6963; Email: kjw1@wustl.edu
      • Principal Investigator: Meagan Jacoby, M.D.
      • Sub-Investigator: Eric Duncavage, M.D.
      • Sub-Investigator: Kelly Bolton, M.D., Ph.D.
      • Sub-Investigator: Matthew Walter, M.D.
      • Sub-Investigator: Timothy Ley, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants seen in Washington University School of Medicine clinics.

Description

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.
• 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm A: Clonal hematopoiesis; Complete several self-administered health assessments at baseline and every 6 months until death.; Cognitive assessment, Gait Speed, grip strength, blood pressure, height, and weight will be performed by a member of the research team at baseline and every 6 months until death.; Peripheral blood draw will occur at baseline and no more than every 6 months until death.; Buccal swabs will occur at baseline and repeated as necessary, but not more than every 6 months until death; May be approached about optional bone marrow biopsy	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; Other: Heart Health and Smoking History from BRFSS questionnaire; 7 items about heart health and smoking history; Baseline and no more frequently than every 6 months until death; Other: Gait Speed; Research coordinator will test gait speed; Baseline and no more frequently than every 6 months until death; Other: Grip Strength; Research coordinator will test grip strength; Baseline and no more frequently than every 6 months until death; Other: Height and Weight measurements; -Baseline and no more frequently than every 6 months until death; Other: Blood pressure measurement; -Baseline and no more frequently than every 6 months until death; Procedure: Optional bone marrow biopsy; -1 optional bone marrow biopsy
Arm B: No clonal hematopoiesis; Complete several self-administered health assessments at baseline and every 6 months until death.; Cognitive assessment, Gait Speed, grip strength, blood pressure, height, and weight will be performed by a member of the research team at baseline and every 6 months until death.; Peripheral blood draw will occur at baseline and no more than every 6 months until death.; Buccal swabs will occur at baseline and repeated as necessary, but not more than every 6 months until death; May be approached about optional bone marrow biopsy	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; Other: Heart Health and Smoking History from BRFSS questionnaire; 7 items about heart health and smoking history; Baseline and no more frequently than every 6 months until death; Other: Gait Speed; Research coordinator will test gait speed; Baseline and no more frequently than every 6 months until death; Other: Grip Strength; Research coordinator will test grip strength; Baseline and no more frequently than every 6 months until death; Other: Height and Weight measurements; -Baseline and no more frequently than every 6 months until death; Other: Blood pressure measurement; -Baseline and no more frequently than every 6 months until death; Procedure: Optional bone marrow biopsy; -1 optional bone marrow biopsy
Arm C: No clonal hematopoiesis & no follow-up; Complete several self-administered health assessments at baseline with no further follow-up; Cognitive assessment, Gait Speed, grip strength, blood pressure, height, and weight will be performed by a member of the research team at baseline with no further follow-up; Peripheral blood draw will occur at baseline with no further follow-up; Buccal swabs will occur at baseline with no further follow-up	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; Other: Heart Health and Smoking History from BRFSS questionnaire; 7 items about heart health and smoking history; Baseline and no more frequently than every 6 months until death; Other: Gait Speed; Research coordinator will test gait speed; Baseline and no more frequently than every 6 months until death; Other: Grip Strength; Research coordinator will test grip strength; Baseline and no more frequently than every 6 months until death; Other: Height and Weight measurements; -Baseline and no more frequently than every 6 months until death; Other: Blood pressure measurement; -Baseline and no more frequently than every 6 months until death
Arm D: Hip replacement; Complete several self-administered health assessments at baseline and every 6 months until death.; Cognitive assessment, Gait Speed, grip strength, blood pressure, height, and weight will be performed by a member of the research team at baseline and every 6 months until death.; Participants with or without clonal hematopoiesis who are undergoing hip replacement; Peripheral blood draw will occur at baseline and no more than every 6 months until death.; Buccal swabs will occur at baseline and repeated as necessary, but not more than every 6 months until death; May be approached about optional bone marrow biopsy
Arm E: Trauma; -Blood sample at the time of admission with initial bloodwork. For inpatient participants, weekly follow-up samples will be drawn with morning phlebotomy. A follow-up sample collection will occur 4-7 weeks after discharge.	Procedure: Blood draw for trauma measurements; -For Arm E only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	-The investigators will sequence the coding region of some or all of the genes in an individual's blood cells and compare results to their matched mouth cells to define hematopoietic-specific mutations. The number of hematopoietic-specific mutations per individual and the frequency of individuals with mutations will be measured.	Estimated to be 10 years
Presence or absence of geriatric syndromes as measured by hematopoietic stem cell mutations	-The presence or absence of geriatric syndromes will be correlated with the mutation status of individuals.	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	-Individuals with mutations will be followed longitudinally to monitor the fraction of hematopoietic cells with mutations, the functional consequences of mutations in their blood cells, and the risk of developing a blood cancer, geriatric syndrome, cardiovascular disease, or other illness.	Estimated to be 10 years
Presence or absence of cardiovascular disease as measured by hematopoietic stem call mutations		Estimated to be 10 years
Determine whether expansion of clonal hematopoiesis (CH) occurs following acute trauma	-Measures change in variant allele fraction	Estimated to be 10 years

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Edward P. Evans Foundation
• Investigators: Principal Investigator: Meagan Jacoby, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2016
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): April 30, 2030

Study Registration Dates

• First Submitted: November 9, 2015
• First Submitted That Met QC Criteria: November 12, 2015
• First Posted (Estimated): November 13, 2015

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Cardiovascular Diseases; Syndrome
• Other Study ID Numbers: 201511019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No