Metabolic Syndrome
Conditions
Keywords
free fatty acids, insulin-mediated, endothelium-dependent vasodilation, metabolic syndrome
Brief summary
This study will test the hypothesis that reducing the release of free fatty acids (FFA) from fat cells will restore insulin-mediated, endothelium-dependent vasodilation in people with the metabolic syndrome.
Detailed description
We hypothesize that acipimox, by decreasing plasma FFA concentrations, will augment endothelium-dependent vasodilation in conduit vessels and insulin-mediated vasodilation in forearm resistance arterioles in vivo, whole-body insulin sensitivity, and AKT (also known as Protein Kinase B) and endothelial nitric oxide synthase (eNOS) phosphorylation in skin biopsy specimens ex vivo, when compared with placebo.
Interventions
DRUGacipimox
250 mg tablet orally every 6 hours for 7 days, with a dose at 7 am on the morning of the study visit
DRUGPlacebo
1 tablet orally every 6 hours for 7 days, with a dose at 7 am on the morning of the study visit
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Adults with metabolic syndrome, defined as the presence of 3 of 5 components of the syndrome as defined by the National Cholesterol Education Program including: * abdominal obesity * elevated fasting blood sugar (110 mg/dL\< glucose \< 126 mg/dL) * low HDL * elevated fasting blood triglycerides (\> 150 mg/dL) * hypertension (BP \> 140/90 mm HG) * Normal cardiovascular examination
Exclusion criteria
* Diabetes mellitus * Untreated hypercholesterolemia (LDL \> 75th percentile for age) * Cigarette smoking within 1 year * Renal insufficiency (creatinine \> 1.4 mg/dl) * Blood dyscrasia * Hepatic dysfunction (ALT \> 2x normal) * Evident coronary/peripheral atherosclerosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow Mediated Vasodilation | After 7 days of each treatment. | Brachial artery response to a 5 minute blood pressure cuff-applied ischemic period |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acipimox First Acipimox treatment QID for 7 days
Acipimox: 250 mg tablet orally every 6 hours for 7 days, with a dose at 7 am on the morning of the study visit
then
Placebo: 1 tablet orally every 6 hours for 7 days, with a dose at 7 am on the morning of the study visit | 17 |
| Placebo First Placebo treatment QID for 7 days
Placebo: 1 tablet orally every 6 hours for 7 days, with a dose at 7 am on the morning of the study visit
then
Acipimox: 250 mg tablet orally every 6 hours for 7 days, with a dose at 7 am on the morning of the study visit | 23 |
| Total | 40 |
Baseline characteristics
| Characteristic | Placebo First | Total | Acipimox First |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 40 Participants | 17 Participants |
| Age, Continuous | 60 years STANDARD_DEVIATION 11 | 56 years STANDARD_DEVIATION 8 | 53 years STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 13 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 25 Participants | 10 Participants |
| Region of Enrollment United States | 23 Participants | 40 Participants | 17 Participants |
| Sex: Female, Male Female | 15 Participants | 26 Participants | 11 Participants |
| Sex: Female, Male Male | 8 Participants | 14 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 0 / 40 | 0 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
Flow Mediated Vasodilation
Brachial artery response to a 5 minute blood pressure cuff-applied ischemic period
Time frame: After 7 days of each treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metabolic Syndrome | Flow Mediated Vasodilation | Placebo | 9.5 percentage of vasodilation | Standard Deviation 6.5 |
| Metabolic Syndrome | Flow Mediated Vasodilation | Acipimox | 10.5 percentage of vasodilation | Standard Deviation 6 |
| Control | Flow Mediated Vasodilation | Placebo | 10.8 percentage of vasodilation | Standard Deviation 4.9 |
| Control | Flow Mediated Vasodilation | Acipimox | 10.9 percentage of vasodilation | Standard Deviation 6.2 |