Effects of Rosuvastatin on the, in Vivo, Kinetic of apoB and apoA1, Using Stable Isotopes, in Type 2 Diabetic Patients

NCT00658463 | Completed Phase 4 DMC

• 1 other identifier: AFSSAPS 041348
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Statins have been shown to reduce significantly the risk for cardiovascular events in patients with type 2 diabetes and statin therapy is largely recommended in this high cardiovascular risk population. However, a residual cardiovascular risk is observed in patients with type 2 diabetes treated by statins. This may be due to the fact that statins do not correct all lipid abnormalities associated with diabetic dyslipidaemia, such as hyperTG and low HDL-cholesterol. Rosuvastatin is a statin which, in addition to its efficacy to reduce LDL-cholesterol, has been show to decrease significantly plasma triglycerides. However, the effects of rosuvastatin on triglyceride rich lipoproteins and HDL remains unknown. The purpose of this study is to analyze the effect rosuvastatin 20 mg on the metabolism of triglyceride rich lipoproteins and HDL in patients with Type 2 diabetes using and in vivo kinetic study of VLDL1-apoB,VLDL2-apoB,IDL-apoB and HDL-apoA1.

Conditions

Diabetes

Keywords

Diabetes; Triglycerides; HDL-cholesterol; kinetic; rosuvastatin

Outcome Measures

Primary Outcomes (1)

• Fractional Catabolic Rates (FCR)of VLDL1-apoB, VLDL2-apoB, IDL-apoB, LDL-apoB and HDL-apoA-I

  At the end of each treatment period (rosuvastatin or placebo)

Secondary Outcomes (1)

• Production Rates (PR) of VLDL1-apoB, VLDL2-apoB, IDL-apoB, LDL-apoB and HDL-apoA-I

  At the end of each treatment period (rosuvastatin or placebo)

Study Arms (2)

1

EXPERIMENTAL

The study is designed with a one-month steady state period with placebo then on a cross-over design with two 6-week periods of placebo or rosuvastatin (20 mg). An in vivo kinetic study will be performed at the end of each 6-week period.

Drug: Rosuvastatin

2

PLACEBO COMPARATOR

The study is designed with a one-month steady state period with placebo then on a cross-over design with two 6-week periods of placebo or rosuvastatin (20 mg). An in vivo kinetic study will be performed at the end of each 6-week period.

Drug: Placebo

Interventions

Rosuvastatin DRUG

rosuvastatin 20 mg/day during 6 weeks versus placebo during 6 weeks in a cross-over design

Also known as: CRESTOR (brand name for rosuvastatin)

1

Placebo DRUG

Placebo

2

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent
• Type 2 diabetic patients (age: 30 to 75 years) treated by one or two oral agents at fixed dose (sulfonylureas, metformin, alpha glucosidase inhibitors) for at least 6 months
• Fasting triglycerides \>= 150 mg/dl
• HDL-C \< 40 mg/dl in men and \< 50 mg/dl in women (NCEP ATPIII lipid criteria for the metabolic syndrome)
• Patients not receiving hypolipidemic agents since at least 6 months
• Diabetic patients with stable HbA1c during the last 6 months
• Subjects willing to follow all study procedures including attendance at clinic for scheduled study visits and compliance with study treatment regimen

You may not qualify if:

• HbA1c \> 9 %
• LDL-C \> 190 mg/dl
• Known heterozygous or homozygous familial hypercholesterolaemia or known type III hyperlipoproteinaemia (familial dysbetalipoproteinaemia
• Documented secondary hypercholesterolaemia of any cause
• History of serious adverse effect or hypersensitivity reactions to other HMG-CoA reductase inhibitors, in particular any history of myopathy
• Pregnant women, women who are breast feeding and women of childbearing potential who are not using chemical or mechanical contraception (prescription oral contraceptives, abstinence, condoms with spermicide, surgical sterilisation, diaphragm with spermicide or intrauterine device) or have positive pregnancy test
• History of malignancy, except subjects who have been disease free for more than 10 years or whose only malignancy has been basal or squamous cell skin carcinoma. Women with a history of cervical dysplasia should be excluded unless 3 consecutive normal cervical smears have subsequently been recorded before entry into the study
• History of alcohol and/or drug abuse
• Active liver disease or hepatic dysfunction as defined by elevations of AST or ALT \* 2 times the ULN. In this case, a second determination of hepatic tests will be performed after one week. If the dysfunction is confirmed, the subject must not be included in the study
• Patient with acromegaly or Cushing syndrome
• Patient receiving insulin treatment
• Use of drugs known to affect lipid metabolism: corticoids, retinoids, antiproteases, estrogens, cyclosporin, glitazones, statins other than rosuvastatin, fibrates, cholestyramine, nicotinic acid, omega 3 or phytosterols
• Renal impairment as defined by creatinine clearance \< 30 ml/min.
• Unstable angina or manifestation of severe atherosclerosis.
• Uncontrolled hypertension defined as either resting diastolic blood pressure of \>95mmHg or resting systolic blood pressure of \>200 mmHg.

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead
• AstraZeneca: collaborator

Study Sites (1)

Centre Hospitalier Universitaire de Dijon

Dijon, 21000, France

Location

Related Publications (1)

• Verges B, Florentin E, Baillot-Rudoni S, Monier S, Petit JM, Rageot D, Gambert P, Duvillard L. Effects of 20 mg rosuvastatin on VLDL1-, VLDL2-, IDL- and LDL-ApoB kinetics in type 2 diabetes. Diabetologia. 2008 Aug;51(8):1382-90. doi: 10.1007/s00125-008-1046-4. Epub 2008 Jun 5.

  PMID: 18535816 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Bruno Vergès, MD

  Centre Hospitalier Universitaire Dijon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 2, 2008
• First Posted: April 15, 2008
• Study Start: January 1, 2006
• Primary Completion: June 1, 2007
• Study Completion: September 1, 2007
• Last Updated: April 15, 2008

Record last verified: 2008-03

Locations

FR (1)