Clinical trial NCT06912984: Heterogeneity of Vascular Adaptations to Exercise With Aging in Women and Men
Official title: Exerkines and the Heterogeneity of Peripheral and Cerebral Vascular Adaptations to Exercise Training With Aging in Women and Men
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aging
Physical Activity
Vascular Health
Keywords: Healthy
Vascular Health
Exercise training
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2025-04-06
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a behavioral intervention involving randomization to either exercise or non-exercise control.
Primary purpose: BASIC_SCIENCE

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.

Detailed 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.

Eligibility criteria: 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;

Primary outcomes:
measure: Endothelial function
timeFrame: Baseline and after 12 weeks
measure: Cerebrovascular function
timeFrame: Baseline and after 12 weeks
Secondary outcomes:
measure: Transcriptome in plasma
timeFrame: Baseline and after 12 weeks
measure: Metabolome in plasma
timeFrame: Baseline and after 12 weeks
measure: Proteome in plasma
timeFrame: Baseline and after 12 weeks
measure: Endothelial microvesicles
timeFrame: Baseline and after 12 weeks
measure: Endothelial cell protein expression
timeFrame: Baseline and after 12 weeks
Other outcomes:
measure: Body composition
timeFrame: Baseline and after 12 weeks
measure: Blood pressure
timeFrame: Baseline and after 12 weeks
measure: Endothelial cell oxidative stress
timeFrame: Baseline and after 12 weeks
measure: Endothelial cell nitric oxide production
timeFrame: Baseline and after 12 weeks
measure: Endothelial cell inflammation
timeFrame: Baseline and after 12 weeks
measure: Endothelial cell eNOS
timeFrame: Baseline and after 12 weeks
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Center, Clinical Translational Research Center and Exercise Research Laboratory
state: Colorado
Study officials:
References: