Implications for Treatment of the Metabolic Syndrome

NCT00666029 | Completed Phase 2 Results

• 4 other identifiers: 4-2-65 (Version 4. 2007-07-03)05/Q1704/38RHM MED 05722005-000512-28
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Metabolic Syndrome

Keywords

metabolic syndrome; Volunteers recruited from the community

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (2)

Atorvastatin

ACTIVE COMPARATOR

Active arm atorvastatin 40 mg. o.d.

Drug: atorvastatin

Placebo

PLACEBO COMPARATOR

Placebo arm dummy pill

Drug: placebo

Interventions

atorvastatin DRUG

40 m.g. o.d. tablets for 6 months

Also known as: Lipitor

Atorvastatin

placebo DRUG

Placebo

Also known as: Dummy

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead

Related Publications (4)

• 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.

  PMID: 19208914 RESULT

• 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.

  PMID: 19929989 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.

  PMID: 20339006 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.

  PMID: 21166928 RESULT

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Professor Christopher Byrne
• Organization: University Hospital Southampton

cdtb@soton.ac.uk

+44 238120 5006

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2008
• First Posted: April 24, 2008
• Study Start: February 1, 2006
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2008
• Last Updated: January 23, 2019
• Results First Posted: June 9, 2016

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share