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- Ensaio Clínico 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
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 3
Contactos e Locais
Locais de estudo
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Bonn, Alemanha, 53105
- Dept. of Clinical Pharmacology, University of Bonn
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Ciência básica
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Lifibrol
Lifibrol (K12.148;
4-(4'-tert.
butylphenyl)-1-(4'-carboxyphenoxy)-2-butanol) given as a 600 mg film-coated tablet
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Lifibrol (K12.148;
4-(4'-tert.
butylphenyl)-1-(4'-carboxyphenoxy)-2-butanol) given as a 600 mg film-coated tablet
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Comparador Ativo: Pravastatin
Pravastatin 40 mg per day
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Pravastatina 40 mg
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
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LDL cholesterol lowering
Prazo: 4 weeks
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4 weeks
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Medidas de resultados secundários
Medida de resultado |
Prazo |
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Changes in other lipoprotein concentrations
Prazo: 4 weeks
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4 weeks
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Heiner K. Berthold, Professor, University of Bonn
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças Metabólicas
- Distúrbios do metabolismo lipídico
- Dislipidemias
- Hipercolesterolemia
- Hiperlipidemias
- Hiperlipoproteinemias
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Antimetabólitos
- Agentes Anticolesterêmicos
- Agentes Hipolipidêmicos
- Agentes Reguladores Lipídicos
- Inibidores da hidroximetilglutaril-CoA redutase
- Pravastatina
Outros números de identificação do estudo
- LIF293/95apoB
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