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| ID | Type | Description | Link |
|---|---|---|---|
| 05/Q1704/38 | Other Identifier | Research Ethics Committee | |
| RHM MED 0572 | Other Identifier | Southampton University Hospitals Trust R&D | |
| 2005-000512-28 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atorvastatin | Active Comparator | Active arm atorvastatin 40 mg. o.d. |
|
| Placebo | Placebo Comparator | Placebo arm dummy pill |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| atorvastatin | Drug | 40 m.g. o.d. tablets for 6 months |
|
|
| 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 |
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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.
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19208914 | Result | Clough GF, Turzyniecka M, Walter L, Krentz AJ, Wild SH, Chipperfield AJ, Gamble J, Byrne CD. Muscle microvascular dysfunction in central obesity is related to muscle insulin insensitivity but is not reversed by high-dose statin treatment. Diabetes. 2009 May;58(5):1185-91. doi: 10.2337/db08-1688. Epub 2009 Feb 10. | |
| 19929989 | Result |
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| ID | Title | Description |
|---|---|---|
| FG000 | Atorvastatin | Active arm atorvastatin 40 mg. o.d. Participants randomised to atorvastatin: 40 m.g. o.d. tablets for 6 months |
| FG001 | Placebo | Placebo arm dummy pill placebo: Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Age 18-75 years, body mass index (BMI) 20-35 kg/m2, with > 3 criteria for the metabolic syndrome.
(One person in the placebo arm did not have complete baseline data).
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| ID | Title | Description |
|---|---|---|
| BG000 | Atorvastatin | Active arm atorvastatin 40 mg. o.d. atorvastatin: 40 m.g. o.d. tablets for 6 months Age 18-75 years, body mass index (BMI) 20-35 kg/m2, with > 3 criteria for the metabolic syndrome , one of which will be hypertriglyceridaemia, i.e. fasting plasma triglycerides >2.0 mmol/L - a cardinal lipid abnormality of the syndrome. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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%. | There was missing data on two participants in the atorvastatin arm and two participants in the placebo arm. | Posted | Mean | Standard Deviation | 10^3 mL*min^-1*100ml^-1*mmHg^-1 | 6 months |
|
Adverse event data collected over 6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Atorvastatin | Active arm atorvastatin 40 mg. o.d. atorvastatin: 40 m.g. o.d. tablets for 6 months |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| muscle ache | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | Muscle ache on medication |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Christopher Byrne | University Hospital Southampton | +44 238120 5006 | cdtb@soton.ac.uk |
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| ID | Term |
|---|---|
| D024821 | Metabolic Syndrome |
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| placebo | Drug | Placebo |
|
|
| Turzyniecka M, Wild SH, Krentz AJ, Chipperfield AJ, Gamble J, Clough GF, Byrne CD. Skeletal muscle microvascular exchange capacity is associated with hyperglycaemia in subjects with central obesity. Diabet Med. 2009 Nov;26(11):1112-9. doi: 10.1111/j.1464-5491.2009.02822.x. |
| 20339006 | Result | Turzyniecka M, Wild SH, Krentz AJ, Chipperfield AJ, Clough GF, Byrne CD. Diastolic function is strongly and independently associated with cardiorespiratory fitness in central obesity. J Appl Physiol (1985). 2010 Jun;108(6):1568-74. doi: 10.1152/japplphysiol.00023.2010. Epub 2010 Mar 25. |
| 21166928 | Result | Clough GF, L'Esperance V, Turzyniecka M, Walter L, Chipperfield AJ, Gamble J, Krentz AJ, Byrne CD. Functional dilator capacity is independently associated with insulin sensitivity and age in central obesity and is not improved by high dose statin treatment. Microcirculation. 2011 Jan;18(1):74-84. doi: 10.1111/j.1549-8719.2010.00070.x. |
| BG001 |
| Placebo |
Placebo arm dummy pill placebo: Placebo Age 18-75 years, body mass index (BMI) 20-35 kg/m2, with > 3 criteria for the metabolic syndrome , one of which will be hypertriglyceridaemia, i.e. fasting plasma triglycerides >2.0 mmol/L - a cardinal lipid abnormality of the syndrome. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Active arm atorvastatin 40 mg. o.d. atorvastatin: 40 m.g. o.d. tablets for 6 months |
| OG001 | Placebo | Placebo arm dummy pill placebo: Placebo |
|
|
| Primary | 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. | There was missing data in four people in the atorvastatin arm and two people in the placebo arm | Posted | Mean | Standard Deviation | mg*kg^-1*min^-1*mIU^-1*L^-1 | 6 months |
|
|
|
| 1 |
| 20 |
| 0 |
| 20 |
| EG001 | Placebo | Placebo arm dummy pill placebo: Placebo | 0 | 20 | 0 | 20 |
|
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| D009750 |
| Nutritional and Metabolic Diseases |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |