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Implications for Treatment of the Metabolic Syndrome

Primary Purpose

Metabolic Syndrome

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
atorvastatin
placebo
Sponsored by
University Hospital Southampton NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Metabolic Syndrome focused on measuring metabolic syndrome, Volunteers recruited from the community

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Atorvastatin

    Placebo

    Arm Description

    Active arm atorvastatin 40 mg. o.d.

    Placebo arm dummy pill

    Outcomes

    Primary Outcome Measures

    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%.
    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.

    Secondary Outcome Measures

    Full Information

    First Posted
    April 22, 2008
    Last Updated
    January 3, 2019
    Sponsor
    University Hospital Southampton NHS Foundation Trust
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00666029
    Brief Title
    Implications for Treatment of the Metabolic Syndrome
    Official Title
    Implications for Treatment of the Metabolic Syndrome
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    February 2006 (undefined)
    Primary Completion Date
    February 2008 (Actual)
    Study Completion Date
    February 2008 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University Hospital Southampton NHS Foundation Trust

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Metabolic Syndrome
    Keywords
    metabolic syndrome, Volunteers recruited from the community

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    40 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Atorvastatin
    Arm Type
    Active Comparator
    Arm Description
    Active arm atorvastatin 40 mg. o.d.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo arm dummy pill
    Intervention Type
    Drug
    Intervention Name(s)
    atorvastatin
    Other Intervention Name(s)
    Lipitor
    Intervention Description
    40 m.g. o.d. tablets for 6 months
    Intervention Type
    Drug
    Intervention Name(s)
    placebo
    Other Intervention Name(s)
    Dummy
    Intervention Description
    Placebo
    Primary Outcome Measure Information:
    Title
    Muscle Microvascular Function
    Description
    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%.
    Time Frame
    6 months
    Title
    Insulin Sensitivity Index
    Description
    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.
    Time Frame
    6 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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.

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    19208914
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    19929989
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    20339006
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    21166928
    Citation
    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.
    Results Reference
    result

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    Implications for Treatment of the Metabolic Syndrome

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