Targeting Inflammation to Treat Cardiovascular Aging (TIVA)
Recruitment status was Recruiting
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States with older age being a primary risk factor. The number of adults greater than age 65 years will almost double to 70 million by 2030, therefore identifying therapeutic strategies for treating or preventing age-related disorders in humans is of major biomedical importance. Cardiovascular aging, defined as a reduction in vascular and cardiac functions with normal aging, occurs even in the absence of CVD risk factors and overt CVD. A key feature of cardiovascular aging is stiffening of the large elastic central arteries such as the aorta (the large blood vessel that leaves the heart and supplies blood to the body). This is important because aortic stiffness directly contributes to clinical problems such as increased blood pressure, reduced blood flow to the heart muscle, and thickening of the heart muscle. Therefore, these clinical consequences are hypothesized to mediate a substantial proportion of the increase in CVD risk in older adults. However, effective drug treatments for aortic stiffness are not currently available and the biological reasons (mechanisms) involved in causing aortic stiffening remain undefined. In addition, the inability of smaller blood vessels to relax, impairment of the heart to relax during the filling phase of the heart cycle (i.e., diastole), and increased blood pressure variability (fluctuations in blood pressure through the day), have all been linked to aortic stiffness. Furthermore, chronic low-grade inflammation with advancing age has been proposed to be a common mechanistic link (i.e., biological reason) between these reductions in cardiovascular function in older adults. Therefore, the investigators propose that inflammation could be a novel therapeutic target to treat cardiovascular aging in older adults. Our central hypothesis is that inflammation mediates the age-related deterioration in cardiovascular functions observed with advancing age through the development of oxidative stress (i.e., imbalance between cellular production of damaging oxygen free radicals vs. protective antioxidants). Our hypothesis predicts that chronic inhibition of inflammation with Salsalate, an FDA-approved anti-inflammatory drug similar to aspirin that is typically used to treat rheumatoid arthritis pain and known to inhibit the 'master' regulator of inflammation in the cell (i.e., nuclear factor kappa B), will improve cardiovascular function in older adults. In addition, the investigators hypothesize that the mechanism for the improvement in cardiovascular function during inhibition of inflammation will be by suppressing oxidative stress. To test our hypothesis, the investigators will randomize older healthy adults (age 50-79 years) to 3 g/day of salsalate or placebo (i.e., pill with inactive substance) pills for 4 weeks and have cardiovascular function measured at baseline and again after 4 weeks.
Drug: Placebo (for salsalate)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Targeting Inflammation to Treat Cardiovascular Aging in Humans (TIVA Study)|
- Carotid-femoral pulse wave velocity (CFPWV) [ Time Frame: Change from baseline CFPWV at 4 weeks ] [ Designated as safety issue: No ]Aortic stiffness
- Brachial artery flow-mediated dilation (FMD) [ Time Frame: Change from baseline brachial artery FMD at 4 weeks ] [ Designated as safety issue: No ]Vascular endothelium-dependent dilation
- Tissue doppler left ventricular relaxation velocity (E') [ Time Frame: Change from baseline E' at 4 weeks ] [ Designated as safety issue: No ]Left ventricular diastolic dysfunction
|Study Start Date:||September 2012|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
Salsalate capsule 1.5 g/day twice per day by mouth for 4 weeks
Placebo Comparator: Placebo
Placebo capsule twice per day by mouth for 4 weeks
Drug: Placebo (for salsalate)
Other Name: Placebo capsule sugar pill to mimic salsalate
Aim 1: To measure aortic wall stiffness and circulating biomarkers of oxidative stress during both acute (IV) intravenous infusions of saline and then the antioxidant vitamin C at baseline and after 4 weeks of salsalate or placebo in healthy older adults. Hypothesis 1: Inhibition of inflammation in older adults will decrease aortic wall stiffness in part by reductions in oxidative stress.
Aim 2: To measure brachial artery endothelium-dependent vasodilation (EDV) and circulating markers of oxidative stress during acute intravenous infusions of saline and then the vitamin C at baseline and after 4 weeks of salsalate or placebo in healthy older adults. Hypothesis 2: Inhibition of inflammation in older adults will improve vascular endothelial vasodilatory function in older adults in part by reductions in oxidative stress.
Aim 3: To measure left ventricular (LV) diastolic relaxation and filling dynamics and circulating markers of oxidative stress during both acute intravenous infusions of saline and then vitamin C at baseline and after 4 weeks of Salsalate or placebo in healthy older adults. Hypothesis 3: Inhibition of inflammation in older adults will improve LV diastolic function in part by reductions in oxidative stress.
Exploratory Aim: To measure 24-hour pressure variability and short-term baroreflex sensitivity before and after 4 weeks of oral Salsalate or placebo treatment in older adults. Exploratory hypothesis: Inhibition of inflammation in older adults will improve cardiovascular autonomic dysregulation in older healthy adults.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01775865
|Contact: Veronica Howsarefirstname.lastname@example.org|
|United States, Iowa|
|University of Iowa||Recruiting|
|Iowa City, Iowa, United States, 52242|
|Contact: Veronica Howsare 319-467-5677 email@example.com|
|Principal Investigator: Gary L Pierce, PhD|
|Sub-Investigator: William G Haynes, MD, PhD|
|Principal Investigator:||Gary L Pierce, PhD||University of Iowa|