Nicotinic Acid Composition of HDL and Arterial Endothelium Function in Premature Coronary Heart Disease and High HDL

NCT ID: NCT01450410

Last Updated: 2013-01-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2013-05-31

Brief Summary

Patients with premature ischemic heart disease (PIHD) and elevated levels of HDL-C present an altered composition of high-density lipoproteins (HDL) which is associated with a loss of their anti-atherogenic effects and of their arterial endothelium function.

Objectives: To analyse if the treatment with nicotinic acid (NA)/Laropiprant can correct the alterations of the HDL composition and endothelial function in patients with PIHD and elevated HDL-C.

Methods: A total of 46 subjects with PIHD who are stable in the 3 months prior to the Study, who continue in treatment with statins and have elevated concentrations of HDL-C (HDL-C ≥2.0mmol/L in females and ≥1.8mmol/L in males) and an LDL-C <100mg/dL. This is a double-blind, randomised Study; after 6 weeks of lifestyle stabilisation, the subjects will be treated with NA or placebo for 16 weeks. At the start and end of treatment, HDL composition will be studied through density gradient preparative ultracentrifuge separation and FBLC (fast protein liquid chromatography) and through the changes in vasodilation induced by the endothelium through ultrasound. Primary endpoint: change in the apoA1 content associated to treatment. Secondary endpoints: variations in the change of the brachial artery diameter with reactive hyperaemia and changes in the content of other lipid and protein components of HDL including apoA2, paraoxonase, amyloid A and LCAT. The changes in HDL composition and endothelial function will be assessed with an analysis of variance with repeated measurements and a 2x2 design.

Conditions

Dyslipidemias

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: QUADRUPLE

Study Groups

Nicotinic Acid

Group Type: ACTIVE_COMPARATOR

Nicotinic acid

Intervention Type: DRUG

Nicotinic acid / laropiprant (Tredaptive 1000 mg/20 mg modified-release tablets). Patients treated with nicotinic acid 1g/day receive one dose of one month and 2 g / day thereafter. Nicotinic acid treatment will last for 12 weeks.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo treatment will last for 12 weeks.

Interventions

Nicotinic acid

Nicotinic acid / laropiprant (Tredaptive 1000 mg/20 mg modified-release tablets). Patients treated with nicotinic acid 1g/day receive one dose of one month and 2 g / day thereafter. Nicotinic acid treatment will last for 12 weeks.

Intervention Type: DRUG

Placebo

Placebo treatment will last for 12 weeks.

Intervention Type: DRUG

Other Intervention Names

Tredaptive; Control

Eligibility Criteria

Inclusion Criteria

• Being male or female
• Age > 25 years
• Have an episode of ischemic heart disease before 55 years in men and in women 65 years
• Serum HDL-C above the 90th percentile of the Spanish population: >=2.0mmol/L in women and >=1.8mmol/L in men (Gomez-Gerique JA, et al. Med Clin (Barc.). 1999, 113: 730-735.)
• Stable treatment with any statin in the past 6 weeks: simvastatin, atorvastatin, rosuvastatin, pravastatin or lovastatin.

Exclusion Criteria

• Uncontrolled hypercholesterolemia or hypertriglyceridemia, LDL-C >2.6mmol/L or triglycerides >2.24mmol/L
• Patients with an episode of ischemic heart disease in the last 3 months
• Patients suffering from acute or chronic inflammatory diseases in the last 3 months
• Treatment with fibrates or omega-3 fatty acids.
• Treatment with steroids or immunosuppressive drugs
• Patients with a contraindication to Tredaptive (Hypersensitivity to the active substances or any of the excipients, significant or unexplained hepatic dysfunction, active peptic ulcer, arterial bleeding).
• Patients treated with drugs that may interact with Tredaptive (Midazolam).

• Minimum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xavier Pinto Sala

OTHER

Sponsor Role: lead

Responsible Party

Xavier Pinto Sala

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Xavier Pintó, PhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitari de Bellvitge

Locations

Unitat Funcional de Risc Vascular. Servei Medicina Interna. Hospital Universitari de Bellvitge.

L'Hospitalet de Llobregat, Barcelona, Spain

Countries

Spain

Other Identifiers

CompHDL2011

Identifier Type: -

Identifier Source: org_study_id