Clinical trial NCT02653638: Blood Brain Flow and Exercise
Official title: Cerebral Vasodilator Responses in Sedentary and Exercise Trained Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Cerebrovascular Circulation
Keywords: Cerebral Vasodilator Function
White Matter Hyperintensity Volume
Default Mode Network Connectivity
Cognitive Function
Cardiorespiratory Fitness
Aging
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2016-01-12
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Cerebral vasodilator responses to CO2 will be measured in young healthy adults, healthy sedentary older adults, and healthy exercise trained older adults. This variable will be examined before and after administering the cyclooxygenase inhibitor indomethacin, which has been shown to blunt cerebral vasodilator responses. In addition, the investigators will examine these counter-regulatory hemodynamic mechanisms to hypoperfusion caused by indomethacin.

Detailed description: Normal aging reduces cerebral blood flow and cognitive function. Aging also appears to alter functional connectivity within the brain, which is associated with cognitive functioning. Observational studies suggest that regular physical activity is associated with higher cerebral blood flow and improved cognitive function. However, the mechanistic links among regular physical activity and cerebral blood flow with advancing age are unknown. In this context, it is unclear if aging or exercise training status alters the neurovascular coupling of blood flow in the brain. Thus, the overall goal of this study is to examine the age-related changes in cerebral vasodilatory capacity, an important homeostatic mechanism and marker for effective regulation of cerebral perfusion, in order to determine how it is mechanistically linked to cognition. Additionally, the investigators will explore the potential beneficial effect of physical activity on the relationships between cerebral vasodilation and cognition in humans.

The research aims are:

1. To determine if cerebral vasodilator responses are affected by age and exercise training status in healthy adults.
2. To compare the effect of cyclooxygenase inhibition on cerebral vasodilator responses in healthy adults.
3. To determine the neurovascular counter-regulatory response to cyclooxygenase inhibition in healthy adults.

Eligibility criteria: Inclusion Criteria:

* Young subjects between 18-35 years old
* Older subjects between 55-75 years old
* Nonsmokers
* Physically active (exercise more than 3 times per week for at least 30 minutes)
* Sedentary (no formal exercise over 1 hour per week).

Exclusion Criteria:

* Outside of the specified age range
* Present with history or evidence of hepatic, renal, or hematological disease; peripheral vascular disease; stroke/neurovascular disease; diabetes; hypertension
* Take medications that indicate hepatic, renal, hematological disease; cardiovascular disease, including hypertension; stroke/neurovascular disease; and diabetes
* Body mass index \>34 kg/m2
* Take physician-prescribed medications that may interact with indomethacin: 1) cardiovascular drugs (e.g. angiotensin-converting-enzyme inhibitor (ACE inhibitors), angiotensin II receptor blockers (ARB's), Diuretics); 2) drugs that would increase bleeding risk (e.g. warfarin, heparin, clopidogrel, rivaroxaban, other NSAIDs); or 3) drugs associated with increased renal toxicity (e.g. cyclosporin, tacrolimus)
* Vulnerable populations (i.e. pregnant women, prisoners, individuals lacking capacity to consent, etc.)

Primary outcomes:
measure: Cerebral Vasodilator Responses
timeFrame: Measurement at baseline
Secondary outcomes:
measure: Cerebral Vasodilator Responses
timeFrame: Measurement beginning 60 minutes post drug and measured through 180 minutes
measure: Blood Pressure
timeFrame: Measurement at baseline and beginning 60 minutes post drug and measured through 180 minutes
Other outcomes:
Locations:
city: Madison
country: United States
facility: Gymnasium-Natatorium
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Jill N Barnes, PhD
role: PRINCIPAL_INVESTIGATOR
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