The PostprAndial eNdothelial Function After Combination of Ezetimibe and simvAstatin Study
Condition: Metabolic Syndrome
MeSH terms: Metabolic Syndrome; Syndrome
Intervention: Simvastatin; Simvastatin/Ezetimibe
Intervention description: 6 weeks of treatment with simvastatin 80 mg; 6 weeks of treatment with simvastatin 10 mg / ezetimibe 10 mg combination
Intervention MeSH terms: Simvastatin; Ezetimibe
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: No
Keywords: Postprandial hypertriglyceridemia; Metabolic syndrome; Endothelial function; Flow mediated dilatation; EndoPAT; Simvastatin; Ezetimibe

Summary:

      The purpose of this study is to investigate whether low-dose simvastatin in combination with
      ezetimibe in comparison to high-dose simvastatin alone, has a beneficial effect on the
      function of the endothelium after an oral fat load in patients with metabolic syndrome.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          1. Patient has a diagnosis of metabolic syndrome according to the modified 2005 AHA/NHLBI
             Scientific Statement with at least:

             - Abdominal obesity defined as:

             *Males: waist circumference >102cm

               -  Females: waist circumference >88cm and two of the following 4 other criteria:

                  - Triglycerides>150 mg/dL

                  - HDL Cholesterol

               -  Males: HDL-C<40 mg/dL

               -  Females:HDL-C<50 mg/dL - Blood pressure

               -  Systolic Blood Pressure ≥130 mmHg or

               -  Diastolic Blood Pressure ≥85 mmHg

                    -  Fasting glucose ≥ 100 mg/dL

          2. Patient understands the study procedures, alternative treatments available, and risks
             involved with the study, and voluntarily agrees to participate by giving written
             informed consent.

          3. Patient is a male or female of 18-79 years of age on the day of signing informed
             consent.

          4. Patient is a non-smoker.

          5. Patient is willing to maintain a stable diet for the duration of the study.

          6. Patient is a postmenopausal female who is not receiving hormone therapy (including
             cyclic and non-cyclical hormone replacement therapy or any estrogen
             antagonist/agonist). Postmenopausal status is defined as (1) no menses for ≥1 year but
             <3 years and confirmed by FSH levels elevated into the postmenopausal range (as
             defined by the designated laboratory) or (2) no menses for at least 3 years.

          7. Patient is naïve to lipid-lowering therapy. Naïve is defined as not being treated with
             a statin, a fibrate or ezetimibe for 3 months before Visit 1 (Week -2)

          8. Patient has a baseline fasting LDL-C level of ≥ 100 mg/dL and < 220 mg/dL, and TG
             level < 400 mg/dL.

        EXCLUSION CRITERIA:

          1. Patient has a BMI > 35.

          2. Patient has hypersensitivity or intolerance to ezetimibe or simvastatin or any
             component of these medications, or to latex.

          3. Patient routinely consumes more than 14 alcoholic drinks per week.

          4. Patient is currently participating or has participated in a study with an
             investigational compound or device within 30 days of signing informed consent.

          5. Patient has a smoking history > 10 pack-years (1 pack-year = at least 20 cigarettes
             per day for a year) OR patient who has smoked within 3 months prior to Visit 1 (Week
             -2).

          6. Patient has exclusionary laboratory values at Visit 1 (Week -2) as listed in the table
             below:

             liver transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase
             [AST]) > 1.5 X ULN with no active liver disease Serum glucose > 7.0 mmol/L Creatine
             kinase(CK)> 2 X ULN Albumin:creatinine ratio > 34 TSH <0.3 mcIU/mL or > 5.0 mcIU/mL

          7. Patient has a history or current evidence of any condition, therapy, lab abnormality
             or other circumstance that might confound the results of the study, or interfere with
             the patient's participation for the full duration of the study, such that it is not in
             the best interest of the patient to participate.

          8. It is not possible to obtain a FMD measurement of sufficient quality at screening
             (Visit 1)

          9. Patient has congestive heart failure, atherosclerotic vascular disease or acute or
             chronic coronary heart disease.

        13. Patient has had a partial ileal bypass, gastric bypass, gastric banding, celiac disease
        or other significant intestinal malabsorption.

        15. Patient has untreated and uncontrolled hypertension with systolic blood pressure >160
        mm Hg or diastolic >100 mm Hg at Visit 1 (Week -2). (Patients with untreated hypertension
        and with office BP at Visit 1 and Visit 2 averaging 160/100 or less can be enrolled).
        Patients using blood pressure-lowering medication are excluded.

        16. Patient has estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 based on
        the 4-variable MDRD

        17. Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids
        or lipoproteins at Visit 1 (Week -2).

        18. Patient has diabetes mellitus defined as a history of diabetes or fasting serum glucose
        > 126 mg/dL.

        For the full exclusion criteria, please check the protocol