Exercise and Mortality in Middle-Aged and Older Adults

Exercise and Mortality in Middle-Aged and Older Adults: A Target Trial Emulation

This protocol is a retrospective study using the observational data of the the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial with over 150,000 participants aged 55-74 years to conduct a target trial emulation to examine the association between self-reported exercise and all cause and cause-specific mortality in apparently healthy, middle-aged and older adults. The PLCO includes assessments of participants' exercise level at two timepoints: at randomization into the PLCO trial (Q0) and 5-7 years after randomization into the PLCO (Q1).

Study Overview

• Status: Not yet recruiting
• Conditions: Overall Survival (All-cause Mortality)
• Intervention / Treatment: Behavioral: Control; Behavioral: Exercise

• Study Type: Observational
• Enrollment (Estimated): 19000

Contacts and Locations

• Study Contact: Name: Lee W Jones, PhD; Phone Number: 626-218-3844; Email: leejones@coh.org
• Study Contact Backup: Name: Lennie Wong, PhD; Phone Number: 626-218-3844; Email: lenniewong@coh.org

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults enrolled into the PLCO screening trial

Description

• Adults enrolled into the PLCO screening trial.
• Among participants reporting low exercise at Q0 (i.e., 0 or less than 1 day/week, with each session <15 minutes in duration), completion of an exercise survey at Q1 as part of PLCO standard trial procedures no later than 5 years after reporting non-exercising status [i.e., no exercise) at Q0.
• No evidence of any of the following absolute contraindications to exercise: uncontrolled hypertension, symptomatic valvular disease; hypertrophic cardiomyopathy; unstable angina pectoris; primary pulmonary hypertension; heart failure; severe arrhythmia; diagnosed dementia; any form of cancer other than non-melanoma, and severe infectious disease.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm 1 - Control; 0 or less than 1 day per week, with each session, on average < 15 minutes.	Behavioral: Control; 0 or less than 1 day per week, with each session, on average < 15 minutes.
Arm 2 - Exercise; >/= 2 days per week of moderate or vigorous intensity, with each session, on average, >/=20 minutes in duration.	Behavioral: Exercise; >/= 2 days per week of moderate or vigorous intensity, with each session, on average, >/=20 minutes in duration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (all-cause mortality)	All-cause mortality (death from any cause) occurring within the follow-up period in the PLCO screening trial.	up to 19 years
Cause-specific mortality	Cause-specific mortality (cancer mortality, mortality from other causes) occurring within the total follow-up period in the PLCO screening trial.	up to 19 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer incidence	Cancer incidence occurring within the total follow-up period in the PLCO screening trial.	up to 19 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Analyses #1	Analyses to examine whether the association between exercise vs. control with all-cause mortality differs as a function of: Sex (male vs. female); Age (<50 years vs. =/>50 years)	up to 19 years
Exploratory Analyses #2	Examine the association between exercise vs. control with incidence of individual cancer types.	up to 19 years

Collaborators and Investigators

• Sponsor: City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): August 6, 2026
• Study Completion (Estimated): August 6, 2026

Study Registration Dates

• First Submitted: November 2, 2025
• First Submitted That Met QC Criteria: November 2, 2025
• First Posted (Actual): November 5, 2025

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: 25603

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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