Atorvastatin and LDL Profile in Non-Insulin Dependent Diabetes Mellitus

Study Overview
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Brief Summary
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The study will investigate the effects of atorvastatin on the concentrations of small, dense LDL and HDL subfractions in patients with diabetes and the underlying mechanisms of these effects.

Detailed Description
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This study was terminated on October 6, 2004. The study terminated prematurely because of a higher screening failure rate than expected. There were no safety or efficacy reasons involved in the decision to terminate.

Official Title
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Impact of Atorvastatin on the Distribution, Composition, and Metabolism of LDL and HDL Subfractions: A Double-blind Placebo-controlled Phase IV Study With Patients Suffering From Combined Hyperlipidemia and Diabetes. Atorvastatin and LDL Profile in NIDDM (ALPIN Study)

Conditions
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Hyperlipidemia, Diabetes Mellitus, Type 2, Non-Insulin Dependent Diabetes Mellitus

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects with a diagnosis of type 2 diabetes mellitus who either have never had a major adverse cardiac event (MACE) diagnosed before or who had a MACE diagnosed at least 6 months ago, but who, according to the judgement of the treating general practitioner, do not receive any hyperlipidemic therapy. Major adverse cardiac events (MACE) include myocardial infarction, coronary angioplasty, coronary artery bypass graft or other revascularization procedures. At Screening: Visit 1 (week -4): Male patients aged >35 and ≤75 years and postmenopausal female patients ≤75 years with a diagnosis of type 2 diabetes mellitus Patients have been euthyroid for at least six months Written informed consent obtained At Visit 2 (week 0): LDL cholesterol ≥130 mg/dl (3.3 mmol/l ) and <190 mg/dl (4.9 mmol/l) Triglycerides <150 mg/dl (1.69 mmol/l ) and <600 mg/dl (11.3 mmol/l) Sum of LDL-5 and LDL-6 cholesterol ≥25 mg/dl (0.65 mmol/l) Follicle stimulating Hormone (FSH) >30 U/l in female patients aged <60 years or FSH >20 U/l in female patients aged ≥60 years Exclusion Criteria: HbA1c > 8.0 Creatine kinase (CK) >5 times the upper limit of normal Patients having taken lipid lowering medication within 8 weeks of the screening visit

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 2<br> | Drug: Placebo<br>* After a run-in phase of 4 weeks eligible patients were randomized at a ratio of 2 : 1 (atorvastatin : placebo). Patients in the placebo group were treated with placebo 20 mg tablets administered once daily orally for 8 weeks.<br>|
| Active Comparator: 1<br> | Drug: Atorvastatin<br>* After a run-in phase of 4 weeks eligible patients were randomized at a ratio of 2 : 1 (atorvastatin : placebo). Patients in the atorvastatin group were treated with atorvastatin 20 mg tablets administered once daily orally for 8 weeks.<br>* Other names: Lipitor, Sortis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in concentration of HDL subfractions 2a and 2b compared with screening (visit 1) |  | 8 weeks (visit 4) | 
| Changes in concentration of LDL subfractions LDL-5 and LDL-6 compared with screening (visit 1) |  | 8 weeks (visit 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in concentration of apolipoprotein B in VLDL, IDL, LDL-1 through LDL-6 and apolipoprotein A I in HDL subfractions 2a, 2b, and HDL-3 compared with screening (visit 1) |  | 8 weeks (visit 4) | 
| Changes in Cholesterol ester transfer protein (CETP), lipoprotein and hepatic lipase activity compared with screening (visit 1) |  | 8 weeks (visit 4) | 
| Changes in concentration of triglycerides, LDL, and HDL compared with screening (visit 1) |  | 8 weeks (visit 4) | 
| Changes in size of LDL subfractions compared with screening (visit 1) |  | 8 weeks (visit 4) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LDL-subfractions, HDL-subfractions, non insulin dependent diabetes mellitus (NIDDM), hyperlipidemia, atorvastatin