Atherosclerosis
Conditions
Keywords
vascular inflammation, endothelium-dependent flow-mediated blood vessel function
Brief summary
The purpose of this study is to determine whether reducing inflammation in blood vessels with an aspirin-like drug called salsalate will improve blood vessel function.
Detailed description
To test the hypothesis that inhibition of I \[kappa\] B kinase \[beta\] (IĸKβ), an inflammatory mediator, by high dose salsalate, will restore insulin-mediated endothelium-dependent vasodilation in subjects with atherosclerosis.
Interventions
DRUGsalsalate
1.5 grams orally 3 times daily
DRUGplacebo
matching placebo
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Non-smoking adult subjects with known atherosclerosis
Exclusion criteria
* Uncontrolled hypertension (\> 140/90 mmHg) * Untreated hypercholesterolemia (LDL \> 160 mg/dL) * Diabetes mellitus * Alanine Aminotransferase \> 150 * Creatinine \> 1.4 mg/dL * Concommitant use of warfarin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow-mediated, Endothelium-dependent Vasodilation | Upon completion of 4 weeks of salsalate and placebo treatment | Flow-mediated, endothelium-dependent vasodilation (percentage increase in brachial artery diameter after a 5 minute ischemic stimulus) measured at the end of placebo treatment and end of salsalate treatment were compared. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atherosclerosis or Metabolic Syndrome Participant flow is identical to that of NCT00762827 (The Impact of Reducing Inflammation on Vascular Function in the Metabolic Syndrome):
The study arms reflect the randomized, placebo-controlled, double-blinded crossover design of the study. In this arm, individuals with either Metabolic Syndrome or Atherosclerosis received either 4.5 g/day salsalate or matching placebo for a 4-week long period. After a 4-week washout interval, these individuals crossed over and received either the salsalate or the placebo (whichever they did not receive in the first study period) for another 4 weeks. | 30 |
| Healthy Participant flow is identical to that of NCT00762827 (The Impact of Reducing Inflammation on Vascular Function in the Metabolic Syndrome):
The study arms reflect the randomized, placebo-controlled, double-blinded crossover design of the study. In this control arm, healthy individuals received either 4.5 g/day salsalate or matching placebo for a 4-week long period. After a 4-week washout interval, these individuals crossed over and received either the salsalate or the placebo (whichever they did not receive in the first study period) for another 4 weeks. | 28 |
| Total | 58 |
Baseline characteristics
| Characteristic | Atherosclerosis or Metabolic Syndrome | Healthy | Total |
|---|---|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 9 | 52 years STANDARD_DEVIATION 13 | 56 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 8 Participants | 12 Participants | 20 Participants |
| Sex: Female, Male Male | 22 Participants | 16 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 58 | 0 / 58 |
| other Total, other adverse events | 6 / 58 | 0 / 58 |
| serious Total, serious adverse events | 0 / 58 | 0 / 58 |
Outcome results
Primary
Flow-mediated, Endothelium-dependent Vasodilation
Flow-mediated, endothelium-dependent vasodilation (percentage increase in brachial artery diameter after a 5 minute ischemic stimulus) measured at the end of placebo treatment and end of salsalate treatment were compared.
Time frame: Upon completion of 4 weeks of salsalate and placebo treatment
Population: The ultrasound data for two subjects was inadequate for analysis. This determination was made prior to unblinding. The data for these two subjects were discarded, leaving 56 subjects for analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Salsalate | Flow-mediated, Endothelium-dependent Vasodilation | 6.8 percentage vasodilation |
| Placebo | Flow-mediated, Endothelium-dependent Vasodilation | 8.7 percentage vasodilation |