Clinical trial NCT03972683: Role of Acetylcholine in Blood Flow Regulation in Healthy Adults: Effects of Age and Exercise Training
Official title: Novel Role of Acetylcholine in Regulating Vascular Tone: Effects of Age and Exercise Training
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Vasoconstriction
Vasodilation
Keywords: Exercise
Lead sponsor: Colorado State University
Sponsor class: OTHER
First posted: 2019-06-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All participants will be studied before and after a handgrip exercise training intervention.
Primary purpose: BASIC_SCIENCE

Brief summary: The overall goal of this study is to address fundamental questions regarding how the molecule acetylcholine interacts with the sympathetic nervous system to regulate blood flow and oxygen delivery to working skeletal muscle in young and older adults. With advancing age, blood vessels supplying active muscle lose their ability to override sympathetic constriction, which limits delivery of oxygen and results in fatigue. Findings from these studies will serve as the foundation for new strategies to improve regional blood flow regulation in older adults and clinical populations, which will increase quality of life and help to preserve functional independence.

Detailed description: The ability of blood vessels to dilate is essential to ensure adequate blood flow and oxygen delivery to active muscle during exercise. With advancing age, exercising muscle loses the ability to overcome vasoconstriction from the sympathetic nervous system, which impairs blood flow and limits exercise tolerance. Thus, understanding the signaling mechanisms that underlie the ability of active muscle to limit sympathetic vasoconstriction will advance our understanding of blood flow regulation in humans and lay the foundation for new strategies to improve blood flow and exercise tolerance in aging and clinical populations.

Therefore, the purpose of this research is to investigate endogenous acetylcholine as an important signaling molecule that regulates blood flow during exercise. The studies will also determine whether a reduced contribution of acetylcholine explains blood flow impairments in older adults. Since exercise training is known to improve acetylcholine signaling, this research will also address whether a handgrip exercise training intervention will improve blood flow regulation. The expected outcomes will provide new insight to the basic physiology underlying vascular control in humans. Furthermore, the findings will provide insight to the age-related decline in blood flow regulation during exercise and will assess the use of an exercise intervention to improve functional outcomes in older individuals.

Participants will be asked to complete several study visits over the course of 8 weeks. Once study eligibility has been determined, participants will report to the Human Performance Clinical Research Laboratory at Colorado State University for a 3 hour visit to assess forearm exercise capacity. In a separate 5 hour visit following an overnight fast, a physician will place a catheter in the brachial artery of the non-dominant arm to assess vascular function. Participants will then complete 7 weeks of handgrip exercise training (four sessions per week) and return to the laboratory for follow-up visits to assess forearm exercise capacity and vascular function.

Eligibility criteria: Inclusion Criteria:

* age 18-35 OR 60-85

Exclusion Criteria:

* recent history of smoking
* body mass index greater than 30
* history of cardiovascular or metabolic disease, including hypertension or diabetes
* medications that may affect outcome measures, such as blood pressure medications or hormone replacement therapy
* high levels of exercise training, particularly with the forearm (such as weightlifting or rock-climbing)

Primary outcomes:
measure: Functional sympatholysis
timeFrame: Baseline (week 0) and post-intervention (week 8)
Secondary outcomes:
measure: Flow-mediated dilation
timeFrame: Baseline (week 0), mid-intervention (week 4), and post-intervention (week 8)
Other outcomes:
Locations:
city: Fort Collins
country: United States
facility: Colorado State University
state: Colorado
Study officials:
affiliation: Colorado State University
name: Frank Dinenno, PhD
role: PRINCIPAL_INVESTIGATOR
References: