Cardiovascular Disease
Conditions
Brief summary
The purpose of this study is to test the hypothesis that aerobic exercise leads to attenuation of the inflammatory response to lipopolysaccharide (LPS) stimulation.
Detailed description
Aerobic exercise - the most widely recommended health behavior - is recognized to reduce the risk of coronary heart disease, so much so that consensus panels routinely include it as part of a cardioprotective regimen for healthy people, but the physiological or mechanistic basis of this protection is uncertain. Understanding the mechanisms has considerable public health significance because it will allow development and testing of targeted interventions to produce comparable cardioprotective effects more directly or in cases where aerobic exercise is not possible. This application proposes to test the hypothesis that aerobic training leads to attenuation of the inflammatory response to LPS stimulation and to examine the role played by exercise-induced increases in vagal activity, improvements in mood, and decreased expression of Toll Receptor 4 (TLR4), the cognate receptor for endotoxin expressed by monocytes.
Interventions
BEHAVIORALaerobic training
12 weeks of aerobic training, 4 times/week
BEHAVIORALWait list
wait list control condition
Sponsors
Feinstein Institute for Medical Research
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 20-45 years old 2. English-speaking 3. Ambulatory 4. BMI \< 32 5. Pre-menopausal (women only) with regular cycle lengths between 26-32 days 6. Average fitness as determined by American Heart Association standards (VO2max \< 43 ml/kg/min for men, \< 37 ml/kg/min for women) VO2max test
Exclusion criteria
1. Use of anti-psychotic medications 2. Current of past major depressive disorder, or total symptom score \> 10 3. BMI\<18 4. Heart disease 5. Hypertension 6. Diabetes mellitus 7. Neurologic disease 8. Smoking 9. Individuals with ischemic heart disease, cardiac arrhythmias, peripheral vascular disease, orthopedic problems such as foot, leg, hip and spine problems,movement disorders, other neurological disorders affecting gait or balance, conditions or treatments associated with impaired thermoregulation, or other medical problems, for which aerobic training would be contraindicated. 10. Use of any medication with autonomic effects 11. Use of birth control medication 12. Ischemic changes, abnormal blood pressure responses, significant ectopy 13. Appears to be at high risk to be unable to adhere to study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| tumor necrosis factor (TNF-alpha) | change from before (pre) to after (post) 12 weeks of training & after 4 weeks of post-deconditioning | TNF-alpha will be measured from whole blood samples stimulated with lipopolysaccharide |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in mood, including depressive symptomatology and negative affect | change from before (pre) to after (post) 12 weeks of training & after 4 weeks of post-deconditioning | — |
| interleukin 1 (IL-1), IL-6, IL-8, IL-10 | change from before (pre) to after (post) 12 weeks of training & after 4 weeks of post-deconditioning | these cytokines will be measured from whole blood samples stimulated with lipopolysaccharide |
| TLR-4 | change from before (pre) to after (post) 12 weeks of training & after 4 weeks of post-deconditioning | TLR-4 will be measured from blood samples |
| cerebral blood volume (CBV) in the dentate gyrus | change from before (pre) to after (post) 12 weeks of training | — |
Countries
United States
Outcome results
None listed