Implications for Treatment of the Metabolic Syndrome

Study Overview
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Brief Summary
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To characterize features of metabolic syndrome in volunteers. To undertake a randomised trial to determine whether treatment with a statin improves muscle microvascular blood flow.

Detailed Description
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To characterise features of the metabolic syndrome, including body fat, insulin sensitivity, and liver fat together with muscle micorvascular blood flow. To undertake a randomised controlled trial of atorvastatin 40 mg. o.d for 6 months to determine whether any of the above measures change with treatment.

Official Title
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Implications for Treatment of the Metabolic Syndrome

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Drug: atorvastatin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Body mass index (BMI) 20-35 kg/m^2 and > 3 criteria for the metabolic syndrome (NCEP III ATP criteria - see below) , one of which will be hypertriglyceridaemia, i.e. fasting plasma triglycerides >2.0 mmol/L - a cardinal lipid abnormality of the syndrome NCEP III ATP metabolic syndrome criteria are: Waist greater than or equal to 102 cm BP greater than 130 / 85 mmHg TG greater than or equal to 1.7mmol/l Glucose greater than or equal to 6.1 mmol/l HDL less than 1.0 mmol/l Exclusion Criteria: Aged <18 years Aged >75 years Known diabetes; renal, liver, or uncontrolled thyroid disease; uncontrolled hypertension; treatment with lipid-modifying drugs; antihypertensive medication; corticosteroid therapy; or hormone replacement therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atorvastatin<br>Active arm atorvastatin 40 mg. o.d. | Drug: atorvastatin<br>* 40 m.g. o.d. tablets for 6 months<br>* Other names: Lipitor;|
| Placebo Comparator: Placebo<br>Placebo arm dummy pill | Drug: placebo<br>* Placebo<br>* Other names: Dummy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle Microvascular Function | Skeletal muscle microvascular function assessed (Filtrass plethysmographic system) using a passive inductive transducer (Compumedics.dwl, Singen, Germany) and a small pressure step venous congestion protocol. Fluid filtration rate (Jv mL min-1 100 mL-1), measured from the slope of limb volume change in response to each pressure step (10 mmHg steps to 60 mmHg around the thigh) over the last 2 minutes of its application, to allow for completion of vascular filling, and plotted against cuff pressure (Pcuff). The slope of this relationship, at pressures above those giving rise to net filtration, is a measure of Kf, microvascular filtration capacity, a function of exchange surface area and permeability. The CV for Kf measurement was 14.5%. | 6 months | 
| Insulin Sensitivity Index | Insulin sensitivity index was assessed during the final steady state 30 minutes of a high dose hyperinsulinaemic euglycaemic clamp (insulin infusion rate 1.5 mIU/kg/min). During this part of the clamp, insulin was infused at 1.5mIU/kg/min and the glucose concentration was maintained at 5 mmol/L using a dextrose infusion. The whole body insulin mediated glucose disposal rate (M value - mg/kg/min) was estimated from the total amount of glucose infused during the last 30 minutes of the clamp. The mean of four serum insulin concentrations was taken during this 30 minutes to determine the steady state insulin concentration (I value - milliunits/litre). M value/I value defined the insulin sensitivity index. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metabolic syndrome, Volunteers recruited from the community