The PostprAndial eNdothelial Function After Combination of Ezetimibe and simvAstatin Study

NCT00817843 | Completed Phase 4 Results

• 2 other identifiers: Vasc-UMCU-10B2008-003908-61
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 5

Brief 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.

Conditions

Metabolic Syndrome

Keywords

Postprandial hypertriglyceridemia; Metabolic syndrome; Endothelial function; Flow mediated dilatation; EndoPAT; Simvastatin; Ezetimibe

Outcome Measures

Primary Outcomes (1)

• Treatment Difference in (Postprandial-Fasting) FMD

  A comparison of the postprandial minus fasting change in FMD under treatment with simvastatin 80 mg versus simvastatin 10/10 mg

  After 6 weeks of treatment

Secondary Outcomes (3)

• Postprandial Endopat Measurement

  after 6 weeks of treatment (crossover)

• Preprandial Endothelial Function Measured by FMD

  after 6 weeks of treatment (crossover)

• Preprandial Endopat Measurement

  after 6 weeks of treatment (crossover)

Study Arms (2)

First Simva 80mg then Simvai/Eze10/10mg

EXPERIMENTAL

First 6 weeks of Simvastatin 80mg, then 6 weeks of Simvastatin/Ezetimibe 10/10mg after 6 weeks of placebo washout

Drug: Simvastatin; Drug: Simvastatin/Ezetimibe

First Simva/Eze 10/10mg then Simva 80mg

EXPERIMENTAL

First 6 weeks of Simvastatin/Ezetimibe 10/10mg, then 6 weeks of Simvastatin 80mg after 6 weeks of placebo washout

Drug: Simvastatin; Drug: Simvastatin/Ezetimibe

Interventions

Simvastatin DRUG

6 weeks of treatment with simvastatin 80 mg

Also known as: Simvastatin (Zocor)

First Simva 80mg then Simvai/Eze10/10mg; First Simva/Eze 10/10mg then Simva 80mg

Simvastatin/Ezetimibe DRUG

6 weeks of treatment with simvastatin 10 mg / ezetimibe 10 mg combination

Also known as: Simvastatin/Ezetimibe (Zetia)

First Simva 80mg then Simvai/Eze10/10mg; First Simva/Eze 10/10mg then Simva 80mg

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patient understands the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
• Patient is a male or female of 18-79 years of age on the day of signing informed consent.
• Patient is a non-smoker.
• Patient is willing to maintain a stable diet for the duration of the study.

You may not qualify if:

• Patient has a BMI \> 35.
• Patient has hypersensitivity or intolerance to ezetimibe or simvastatin or any component of these medications, or to latex.
• Patient routinely consumes more than 14 alcoholic drinks per week.
• Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent.
• 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).
• 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
• 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.
• It is not possible to obtain a FMD measurement of sufficient quality at screening (Visit 1)
• Patient has congestive heart failure, atherosclerotic vascular disease or acute or chronic coronary heart disease.
• \. Patient has had a partial ileal bypass, gastric bypass, gastric banding, celiac disease or other significant intestinal malabsorption.
• \. 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.
• \. Patient has estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2 based on the 4-variable MDRD
• \. Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins at Visit 1 (Week -2).
• \. Patient has diabetes mellitus defined as a history of diabetes or fasting serum glucose \> 126 mg/dL.

Sponsors & Collaborators

• dr.Frank L.J. Visseren: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

Department of Vascular Medicine UMC Utrecht

Utrecht, Utrecht, 3584 CX, Netherlands

Location

Academic Medical Center

Amsterdam, 1005 AZ, Netherlands

Location

Vascular Research Center Hoorn

Hoorn, 1624 NP, Netherlands

Location

Tweesteden Ziekenhuis

Waalwijk, 5141 BM, Netherlands

Location

Hospital Arnau de Vilanova

Lleida, E-25198, Spain

Location

Related Publications (1)

• Olijhoek JK, Hajer GR, van der Graaf Y, Dallinga-Thie GM, Visseren FL. The effects of low-dose simvastatin and ezetimibe compared to high-dose simvastatin alone on post-fat load endothelial function in patients with metabolic syndrome: a randomized double-blind crossover trial. J Cardiovasc Pharmacol. 2008 Aug;52(2):145-50. doi: 10.1097/FJC.0b013e31817ffe76.

  PMID: 18670365 BACKGROUND

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Simvastatin; Ezetimibe, Simvastatin Drug Combination; Ezetimibe

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Limitations and Caveats

One limitation is that the study was conducted in obese patients with the metabolic syndrome.

Results Point of Contact

• Title: Professor F.L.J. Visseren, MD PhD
• Organization: UMC Utrecht

f.l.j.visseren@umcutrecht.nl

0031-88-7555555

Study Officials

• Frank LJ Visseren, MD PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor F.L.J. Visseren, MD PhD, head of department of Vascular Medicine

Study Record Dates

• First Submitted: January 6, 2009
• First Posted: January 7, 2009
• Study Start: April 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: January 9, 2013
• Results First Posted: January 9, 2013

Record last verified: 2013-01

Locations

NL (4); ES (1)