- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01057654
A Study Comparing the Mechanisms of Action of Lifibrol and Pravastatin
A Stable-isotope Study in Healthy Normolipidemic Volunteers Comparing the Mechanisms of Action of Lifibrol and Pravastatin
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Elevated lipoprotein concentrations are a major risk factor for the development of atherosclerotic cardiovascular disease. Effective reduction of low density lipoprotein (LDL)-cholesterol concentrations has been shown to greatly reduce this risk. The most widely used lipid-lowering agents are the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), which have been shown to reduce morbidity and mortality from coronary heart disease (CHD) in large prospective clinical trials. However, despite significant LDL-C reduction approximately 70% of the events are still not avoided and the search for improved or alternative lipid-modifying drug therapies continuous. HDL-C has been addressed as a potential modifiable target for decreasing this residual risk, since a low HDL-C concentration is an acknowledged independent risk factor for CHD. However, recent studies showed that an increase in HDL-C concentrations was surprisingly not associated with a decrease in atherosclerosis, but with a possible increase. Therefore it seems that not the concentrations of HDL-C should be targeted but HDL function in reverse cholesterol transport.
Lifibrol is a lipid-modifying drug which has been shown to improve HDL particle flux via increased apoA-I production, while not having HDL-raising properties. Furthermore, it decreases dose-dependently LDL-C by up to 40%. It is of major interest to clarify the, apparently unique, mechanisms of action of a compound, whose LDL-lowering effects are comparable in magnitude to the ones of statins.
The mechanisms of lifibrol's LDL-lowering effects are not completely clarified. There is evidence suggesting that it increases hepatic LDL receptor expression by a sterol-independent mechanism, i.e. not through a reduction in cholesterol synthesis, the mechanism of action of statins. ApoB turnover studies have indicated that increased catabolism of LDL rather than a decrease in hepatic apoB production may be responsible for its cholesterol-lowering effects. Since apoB metabolism and cholesterol synthesis are closely related, we designed a study to investigate the effects of lifibrol on the metabolism of apoB-100-containing lipoproteins and on endogenous sterol synthesis in parallel, using stable isotope methods. In addition, since lifibrol may inhibit cholesterol synthesis at steps earlier than HMG-CoA reductase, we investigated [13C]acetate catabolism analyzing 13CO2 appearance in breath. The HMG-CoA-reductase inhibitor pravastatin was used as comparator, since its mode of action is well characterized. The principle questions addressed were (i) whether lifibrol exerts its cholesterol-lowering effects through decreased synthesis/enhanced catabolism of apoB-100-containing lipoproteins or through inhibition of sterol de novo synthesis and (ii) whether these effects are interrelated.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Bonn, Germany, 53105
- Dept. of Clinical Pharmacology, University of Bonn
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- male volunteers
- 18 to 35 years old
- good clinical condition
- normal eating habits
- mental abilities to be able to understand the study procedures
- written informed consent
Exclusion Criteria:
- relevant pathological findings in the baseline examination
- known allergic predisposition
- concomitant drugs
- alcohol or nicotine abuse
- participation in other clinical trials in the last 30 days
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Lifibrol
Lifibrol (K12.148;
4-(4'-tert.
butylphenyl)-1-(4'-carboxyphenoxy)-2-butanol) given as a 600 mg film-coated tablet
|
Lifibrol (K12.148;
4-(4'-tert.
butylphenyl)-1-(4'-carboxyphenoxy)-2-butanol) given as a 600 mg film-coated tablet
|
Active Comparator: Pravastatin
Pravastatin 40 mg per day
|
Pravastatin 40 mg
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
LDL cholesterol lowering
Time Frame: 4 weeks
|
4 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Changes in other lipoprotein concentrations
Time Frame: 4 weeks
|
4 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Heiner K. Berthold, Professor, University of Bonn
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Lipid Metabolism Disorders
- Dyslipidemias
- Hypercholesterolemia
- Hyperlipidemias
- Hyperlipoproteinemias
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Pravastatin
Other Study ID Numbers
- LIF293/95apoB
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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