Effects on NF-κB Activity: High Dose Simvastatin Versus Combination Therapy With Ezetimibe

Study Overview
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Brief Summary
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Lowering LDL cholesterol by statins has been proven to be associated with reduction of proinflammatory regulators e.g. activation of the transcription factor NF-ĸB. Up to now the effects of newer cholesterol lowering agents such as ezetemibe with respect to their anti-inflammatory potential are less intensively studied. Therefore the investigators analyzed whether equipotent LDL-lowering therapy with simvastatin alone and in combination with ezetimibe have comparable effects on NF-ĸB-activation in peripheral blood mononuclear cells (PBMCs) of patients with type 2 diabetes.

Official Title
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Effects on NF-κB Activity: High Dose Simvastatin Versus Combination Therapy With Ezetimibe

Conditions
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Type 2 Diabetes, Inflammation

Intervention / Treatment
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* Drug: Simvastatin 80 mg
* Drug: Sim10/Eze10
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 35 to 80 years old type 2 diabetes HbA1c value between 6.0 % and 9.0 % elevated LDL-c values > 100 mg/dl with no lipid lowering treatment within the last six month Exclusion Criteria: refused informed consent

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Treatment with placebo over 8 weeks | Drug: Placebo<br>* treatment with placebo over 8 weeks<br>|
| Active Comparator: Simvastatin 80 mg<br>treatment with 80 mg of simvastatin over 8 weeks | Drug: Simvastatin 80 mg<br>* treatment with 80 mg of simvastatin over a period of 8 weeks<br>* Other names: simvastatin;|
| Active Comparator: Sim10/Eze10<br>treatment with 10 mg of simvastatin in combination with 10 mg ezetimibe over 8 weeks | Drug: Sim10/Eze10<br>* treatment with combination of simvastatin 10 mg and ezetimibe 10 mg<br>* Other names: inegy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NF-kappa B binding activity | The binding activity of nuclear transcription factor nuclear factor kappa B (NF-kappa B)will be measured in patients with type 2 diabetes before and after 8 weeks while under study treatment. Analysis will be done with electrophoretic mobility shift assay. Nuclear extract, which is necessary, will be generated from peripheral blood mononuclear cells. | up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory markers | Blood levels of high sensitivity CRP and interleukin-6 will be measured before study start and after 8 weeks while under study medication. | up to 5 years |