The Effects of Hypolipemic and Antidiabetic Treatment on Cytokines

Study Overview
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Brief Summary
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The study is planned to show whether combined hypolipemic and antidiabetic therapy with various daily dosages influence the fasting plasma glucose, insulin sensitivity and proinflammatory cytokines in diabetic and dyslipidemic subjects.

Official Title
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Effects of High and Low Doses of Metformin, Fenofibrate and Simvastatin, Administered Together and in Sequence With Lifestyle Intervention on Lipid Profile, Glucose Metabolism, Low-grade Inflammation and Hemostasis in Patient's Blood Plasma in Type 2 Diabetic Patients With Serious Mixed Dyslipidemia

Conditions
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Diabetes, Dyslipidemia, Inflammation, Cytokines

Intervention / Treatment
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* Drug: Metformin 1000mg, simvastatin 10mg and fenofibrate 100mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age (35-64yr) Primary hyperlipidemia (Total cholesterol >200mg/dl, Triglycerides >150mg/dl) Type 2 Diabetes For women: Menopause (>12 months) Post hysterectomy Mechanical contraception Obtained informed consent Exclusion Criteria: Secondary hyperlipidemia Morbid obesity (BMI>40kg/m2) Alcohol or drug abuse Acute or chronic inflammation Congestive Heart Failure (NYHA III or IV) Unstable Ischaemic Heart Disease Moderate or severe hypertension Cancer in less than 5 years Chronic kidney disease (stage III-V) Liver failure Oral contraception Not compliant patient Laboratory results: alanine transferase (>3xULN) creatine kinase (>5xULN) haemoglobin (<10/dl) PLT (<100G/l) WBC (<3,5G/l or >10G/l)

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: M1000 S10 F100<br>metformin 1000mg, fenofibrate 100mg and simvastatin 10mg | Drug: Metformin 1000mg, simvastatin 10mg and fenofibrate 100mg<br>* Patient will take three pill consisting of metformin 1000mg, simvastatin 10mg and fenofibrate 100mg.<br>|
| Active Comparator: M1000 S10 F267<br>metformin 1000mg, fenofibrate 267mg and simvastatin 10mg | Drug: Metformin 1000mg, simvastatin 10mg and fenofibrate 100mg<br>* Patient will take three pill consisting of metformin 1000mg, simvastatin 10mg and fenofibrate 100mg.<br>|
| Active Comparator: M1000 S40 F100<br>metformin 1000mg, fenofibrate 100mg and simvastatin 40mg | Drug: Metformin 1000mg, simvastatin 10mg and fenofibrate 100mg<br>* Patient will take three pill consisting of metformin 1000mg, simvastatin 10mg and fenofibrate 100mg.<br>|
| Active Comparator: M1000 S40 F267<br>metformin 1000mg, fenofibrate 267mg and simvastatin 40mg | Drug: Metformin 1000mg, simvastatin 10mg and fenofibrate 100mg<br>* Patient will take three pill consisting of metformin 1000mg, simvastatin 10mg and fenofibrate 100mg.<br>|
| Active Comparator: M2500 S10 F100<br>metformin 2500mg, fenofibrate 100mg and simvastatin 10mg | Drug: Metformin 1000mg, simvastatin 10mg and fenofibrate 100mg<br>* Patient will take three pill consisting of metformin 1000mg, simvastatin 10mg and fenofibrate 100mg.<br>|
| Active Comparator: M2500 S10 F267<br>metformin 2500mg, fenofibrate 267mg and simvastatin 10mg | Drug: Metformin 1000mg, simvastatin 10mg and fenofibrate 100mg<br>* Patient will take three pill consisting of metformin 1000mg, simvastatin 10mg and fenofibrate 100mg.<br>|
| Active Comparator: M2500 S40 F267<br>metformin 2500mg, fenofibrate 267mg and simvastatin 40mg | Drug: Metformin 1000mg, simvastatin 10mg and fenofibrate 100mg<br>* Patient will take three pill consisting of metformin 1000mg, simvastatin 10mg and fenofibrate 100mg.<br>|
| Active Comparator: M2500 S40 F100<br>metformin 2500mg, fenofibrate 100mg and simvastatin 40mg | Drug: Metformin 1000mg, simvastatin 10mg and fenofibrate 100mg<br>* Patient will take three pill consisting of metformin 1000mg, simvastatin 10mg and fenofibrate 100mg.<br>|
| Placebo Comparator: Therapeutic Lifestyle Change<br>Only therapeutic lifestyle change | Drug: Metformin 1000mg, simvastatin 10mg and fenofibrate 100mg<br>* Patient will take three pill consisting of metformin 1000mg, simvastatin 10mg and fenofibrate 100mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antiinflammatory effects of combined antidiabetic and hypolipemic treatment | As inflammatory effects we measure the difference in serum concentration before and after the treatment of the following proinflammatory cytokines: Interleukin 1 TNF alpha Interleukin 6 Interleukin 10 hsCRP | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Assesed by HOMA (Homeostatic Model of Assessment) | 30 days | 
| Coagulation parameters | Assessed using: Fibrinogen PAI-1 | 30 days |