Heterogeneity of Vascular Adaptations to Exercise With Aging in Women and Men

NCT06912984 | Recruiting DMC

• 2 other identifiers: 24-1316R01AG089069
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the proposed study is to understand the reasons for the variability in aerobic exercise (AE) training benefits on the vasculature in middle-age and older (MA/O) adults, including differences between men and women. To achieve this goal, a mechanistic randomized controlled (RCT) will be conducted, in which adults are randomized to 12-weeks intervention of AE or no-exercise Control. Our overall hypothesis is that the exercise response variation in vascular benefits is related to age and sex differences in the biological changes underlying vascular aging and/or the molecular transducers (i.e., circulating molecules) that communicate and coordinate the effects of AE on the vasculature in the periphery and brain. Because this is a mechanistic trial, the overall goal is not a single health-related outcome. Rather, the goal is to advance our understanding of the molecular signals and pathways underlying the systemic and local effects of AE on vascular health that may explain the variability in AE responses with age and sex. This knowledge will allow for the development of personalized age- and sex-specific AE recommendations, and/or provide insights into molecular targets that can be manipulated to enhance and/or mimic exercise in non-responders or in persons unable to exercise.

Conditions

Aging; Physical Activity; Vascular Health

Keywords

Healthy; Vascular Health; Exercise training

Outcome Measures

Primary Outcomes (2)

• Endothelial function

  Changes in brachial artery flow-mediated dilation calculated as %

  Baseline and after 12 weeks

• Cerebrovascular function

  Changes in cerebrovascular reactivity to a hypercapnic stimulus calculated as cm/s/mmHg

  Baseline and after 12 weeks

Secondary Outcomes (5)

• Transcriptome in plasma

  Baseline and after 12 weeks

• Metabolome in plasma

  Baseline and after 12 weeks

• Proteome in plasma

  Baseline and after 12 weeks

• Endothelial microvesicles

  Baseline and after 12 weeks

• Endothelial cell protein expression

  Baseline and after 12 weeks

Other Outcomes (6)

• Body composition

  Baseline and after 12 weeks

• Blood pressure

  Baseline and after 12 weeks

• Endothelial cell oxidative stress

  Baseline and after 12 weeks

Study Arms (2)

Aerobic Exercise Training

EXPERIMENTAL

Participants randomized to this arm will engage in moderate-intensity aerobic exercise (AE) training program consisting of treadmill walking/running and upright cycling. The training program involves 3 training sessions per week for 12 weeks. Each session will be ≈ 60 minutes in duration. During the 12-week intervention, participants will maintain their typical diet and daily physical activity, aside from the prescribed training program. Participants will periodically check in with the study team to assess any changes in weight and report any changes in their physical activity, diet, or medications.

Behavioral: Aerobic Exercise Training

Control

NO INTERVENTION

Participants randomized to this arm will serve as the non-exercise control group. During the 12-week control period, participants will maintain their typical daily physical activity and diet. Participants will periodically check in with the study team to assess any changes in weight and report any changes in their physical activity, diet, or medications.

Interventions

Aerobic Exercise Training BEHAVIORAL

The aerobic exercise training intervention will consist of moderate-intensity aerobic exercise training program consisting of treadmill walking/running and upright cycling. The training program involves 3 training sessions per week for 12 weeks. Each session will be ≈ 60 minutes in duration.

Aerobic Exercise Training

Eligibility Criteria

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

You may qualify if:

• Ability to provide consent;
• Man or woman \>= 18 years;
• Willing to be randomized to an exercise or control intervention;
• No orthopedic limitations that would prevent the volunteer from performing treadmill or cycling exercise;
• No use of hormone therapy in postmenopausal women or in men (note, hormonal contraceptives in premenopausal women will be allowed);
• Healthy, as determined by medical history, physical examination, standard blood chemistries and ECG at rest and during a physician monitored graded exercise treadmill test;
• Sedentary or recreationally active (\<2 days/wk vigorous activity);
• No use of medications that might influence cardiovascular function (e.g., blood pressure and lipid lowering medications, metformin, insulin, sulfonylureas, etc.);
• No use of vitamins, supplements or anti-inflammatory medications, or willing to stop 1 month prior to enrollment and for the duration of the study;

You may not qualify if:

• Contraindications to aerobic exercise;
• Diabetic or fasted glucose \>126 mg/dL;
• Resting blood pressure \>= 140/90 mmHg;
• Current or past history of cancer other than skin cancer;
• Preexisting or active cardiac, renal or hepatic disease;
• History of stomach ulcer or bleeding or epilepsy or nervous system and/or seizure disorder;
• Active or chronic infection;
• An abnormal resting ECG, angina and/or ECG evidence of acute myocardial ischemia during the exercise test (development of ST-segment depression of more than 0.3 mV that is either horizontal, downsloping, or slowly upsloping- less than 1 mvolt/sec and lasts more than 0.08 sec; ST elevation; chest pain or discomfort), bundle branch block, AV block greater than first degree, arrhythmias;
• Thyroid dysfunction, defined as ultrasensitive TSH \<0.5 or \>5 mU/L. Participants with abnormal TSH values will be reconsidered for participation after follow-up with their PCP and initiation of thyroid replacement medications for at least 3 months;
• Smoking or tobacco use;
• Alcohol consumption \> 14 drinks/week;
• Body mass index \> 39kg/m2;

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Colorado Anschutz Medical Center, Clinical Translational Research Center and Exercise Research Laboratory

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Motor Activity

Condition Hierarchy (Ancestors)

Behavior

Central Study Contacts

Kerrie Moreau, PhD

CONTACT

(303)-724-1914; kerrie.moreau@cuanschutz.edu

Claire Cox

CONTACT

303-724-1396; claire.cox@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will not be blinded to the group assignment (Exercise or Control); Investigator and outcomes assessor will be blinded until all analysis are completed.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a behavioral intervention involving randomization to either exercise or non-exercise control.

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: April 6, 2025
• Study Start: May 28, 2025
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): July 31, 2029
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)