Metabolic Syndrome
Conditions
Keywords
Metabolic Syndrome, LDL subfraction L5, The reduction of LDL in patients with Metabolic Syndrome, The prevalence of L5 in patients with Metabolic Syndrome, The reduction of L5 in patients with Metabolic Syndrome
Brief summary
The purpose of this study is: * To identify the common factor for L5 prevalence in patients with Metabolic Syndrome. * To determine whether Ezetimibe, Simvastatin, and Vytorin can correct the L5- promoting factor and reduce L5 in Metabolic Syndrome patients.
Detailed description
Epidemiological evidence indicates that metabolic syndrome (MS) is a strong predisposing condition for atherosclerosis. Elevation of plasma low-density lipoprotein (LDL) cholesterol(LDL-C) concentration is the most important risk factor for atherosclerosis; however, LDL-C elevation is not a criterion for metabolic syndrome, raising the question of LDL's role in the syndrome's association with atherosclerosis. L5, a highly electronegative and mildly oxidized LDL subfraction that we recently isolated from hypercholesterolemic human plasma, may provide a key to answering this question. In cultured vascular endothelial cells (EC), L5 inhibits proliferation and induces apoptosis and monocyte-EC adhesion. In our preliminary studies, L5 could also be detected in patients with MS without elevated LDL-C. Because other LDL subfractions were harmless to EC, the presence of MS-L5 prompted us to hypothesize that the atherogenic role of LDL is not solely determined by plasma LDL-C concentration, but more importantly, by its composition. The proposed study is designed to test this hypothesis. The first question we will address is what lipid factor determines the prevalence of L5 in MS. Subsequently, we will examine whether treatment with selected medicines can effectively reduce L5 in MS patients by correcting the factor favorable for L5 formation. We are in the process of identifying the active components of L5 to fully characterize the atherogenic role of L5 in MS,. In the current proposal, we focus our interest on the efficacy of Ezetimibe, Simvastatin, and Vytorin in reducing L5 from the plasma of MS patients.
Interventions
DRUGSimvastatin
Simvastatin 20mg daily for 3 months.
DRUGVytorin
Vytorin 20/10mg daily for 3 months.
DRUGPlacebo
Placebo one tablet daily times 3 months.
DRUGEzetimibe
Ezetimibe 10mg daily for 3 months.
Sponsors
Merck Sharp & Dohme LLC
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Intervention model description
Randomized, placebo-controlled clinical trial with 4 arms
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants who meet 3 or more of the 5 criteria specified in the ATPIII guidelines will be recruited. * The 5 criteria are: 1. abdominal obesity (men\>40 inches, women \>35 inches); 2. TG\> 150mg/dL; 3. low HDL-C (men \< 40mg/dL, women \< 50 mg/dL); 4. high blood pressure (\>or=130/\>or=85 mmHg); 5. fasting glucose \> or = 110mg/dL. * People with different ethnic backgrounds will be included.
Exclusion criteria
* symptomatic coronary artery disease * peripheral vascular disease * cerebral ischemia (stroke) * smoking * hypothyroidism * kidney diseases * consumption of antioxidation supplements/drugs or use of lipid-lowering drugs in the last 3 months * women who are pregnant, nursing, or planning to become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| L5 Concentration in Metabolic Syndrome Patients | 0 months, at the start | Patient's blood samples were collected before treatment. L5 were purified by ultracentrifugation then FPLC. Quantification analysis will indicate the L5 concentration (mg/dL) per group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| L5 Concentration After Treatment of Ezetimibe, Simvastatin, or Vytorin in Metabolic Syndrome Patients | 3 months | Patient's blood samples were collected at the corresponding time point for L5 purification. L5 quantification and characterization were investigated with chemical analysis, proteomics and in-vitro cell signaling analysis. Final data analysis will determine total L5 concentration (mg/dL). |
Countries
United States
Participant flow
Recruitment details
Of 30 enrolled participants, 24 met inclusion criteria and were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe Participants take Ezetimibe 10mg daily for 3 months. N= 6 Ezetimibe: 10mg tablet | 6 |
| Simvastatin Participants take Simvastatin 20mg daily for 3 months. N=6 Simvastatin: 20mg tablet | 6 |
| Vytorin Participants take Vytorin 20/10mg daily for 3 months. N=6 Vytorin: 20/10mg tablet | 6 |
| Placebo Participants take Placebo tab 1 daily for 3 months. N=6 Placebo: 1 tablet | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | Simvastatin | Vytorin | Placebo | Ezetimibe | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
| Age, Continuous | 49.5 years STANDARD_DEVIATION 7.71 | 52.8 years STANDARD_DEVIATION 4.22 | 52 years STANDARD_DEVIATION 9.01 | 53.3 years STANDARD_DEVIATION 4.61 | 52 years STANDARD_DEVIATION 6.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 0 Participants | 4 Participants | 8 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 6 participants | 6 participants | 24 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
L5 Concentration in Metabolic Syndrome Patients
Patient's blood samples were collected before treatment. L5 were purified by ultracentrifugation then FPLC. Quantification analysis will indicate the L5 concentration (mg/dL) per group.
Time frame: 0 months, at the start
Population: all participants assigned to Ezetimibe, Simvastatin, Vytorin and Placebo will receive the corresponding treatment according to the assigned group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | L5 Concentration in Metabolic Syndrome Patients | 35.97 mg/dL | Standard Deviation 28.87 |
| Simvastatin | L5 Concentration in Metabolic Syndrome Patients | 17.8233 mg/dL | Standard Deviation 14.4558 |
| Vytorin | L5 Concentration in Metabolic Syndrome Patients | 29.736 mg/dL | Standard Deviation 21.143 |
| Placebo | L5 Concentration in Metabolic Syndrome Patients | 23.1 mg/dL | Standard Deviation 18.338 |
Secondary
L5 Concentration After Treatment of Ezetimibe, Simvastatin, or Vytorin in Metabolic Syndrome Patients
Patient's blood samples were collected at the corresponding time point for L5 purification. L5 quantification and characterization were investigated with chemical analysis, proteomics and in-vitro cell signaling analysis. Final data analysis will determine total L5 concentration (mg/dL).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe | L5 Concentration After Treatment of Ezetimibe, Simvastatin, or Vytorin in Metabolic Syndrome Patients | 30.17 mg/dL | Standard Deviation 21.66 |
| Simvastatin | L5 Concentration After Treatment of Ezetimibe, Simvastatin, or Vytorin in Metabolic Syndrome Patients | 19.19 mg/dL | Standard Deviation 19.4648 |
| Vytorin | L5 Concentration After Treatment of Ezetimibe, Simvastatin, or Vytorin in Metabolic Syndrome Patients | 14.17 mg/dL | Standard Deviation 16.721 |
| Placebo | L5 Concentration After Treatment of Ezetimibe, Simvastatin, or Vytorin in Metabolic Syndrome Patients | 15.15 mg/dL | Standard Deviation 15.027 |