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

University of Colorado Denver (CU Denver)

Status: Enrolling

Conditions: Aging; Physical Activity; Vascular Health

Treatments: Behavioral: Aerobic Exercise Training

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06912984

R01AG089069 (U.S. NIH Grant/Contract)

24-1316

Details and patient eligibility

About

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.

Full description

This is a single-blind (investigator and outcomes assessor), parallel-design clinical trial to determine whether heterogeneity in the biology of aging and molecular transducers with acute and chronic AE mediates AE response variation in peripheral endothelial function (brachial artery flow-mediated dilation [FMD]; primary outcome) and cerebrovascular function (cerebrovascular reactivity to a hypercapnic stimulus [CVRCO2]; primary outcome) with age and between sexes. Biospecimens (blood, vascular endothelial cells) obtained: (a) before, during (blood only), and 0.25, 0.5 and 2 h (blood only) after acute treadmill AE (60-80% VO2max, 40 minutes); (b) before and after a 12-week AE intervention (3 d/week, 60-80% heart rate reserve, ~1 h duration); (c) or non-exercise control will be assayed for transcriptomic (mRNA transcripts), proteomic, metabolomic (small metabolites) and EMVs and their cargo (e.g., microRNA) in sex balanced groups of young (18-39 years), middle-aged (40-59 years) and older (≥60 years) adults. There is also collection of cardiorespiratory fitness, blood pressure, body composition (measured by dual-energy x-ray absorptiometry), physical activity and sleep using wearable devices, and health status questionnaires.

Enrollment: 242 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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;

Exclusion criteria

• 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;

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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242 participants in 2 patient groups

Aerobic Exercise Training

Experimental group

Description:

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.

Treatment:

Behavioral: Aerobic Exercise Training

Control

No Intervention group

Description:

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.