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

Dyslipidemias Clinical Trial

— 11MSP011  

Official title:

Efecto Del ácido nicotínico Sobre la composición de Las lipoproteínas de Alta Densidad (HDL) y la función Del Endotelio Arterial en Los Pacientes Con cardiopatía isquémica Prematura y Concentraciones Elevadas de Colesterol-HDL

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01450410
• Other study ID #: CompHDL2011
• Status: Terminated
• Phase: Phase 4
• First received: October 7, 2011
• Last updated: January 28, 2013
• Start date: July 2012
• Est. completion date: May 2013

Study information

• Verified date: November 2011
• Source: Hospital Universitari de Bellvitge
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: May 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years and older

Eligibility

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).

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Dyslipidemias

Intervention

Drug:
• 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.
• Placebo
Placebo treatment will last for 12 weeks.

Locations

Country	Name	City	State
Spain	Unitat Funcional de Risc Vascular. Servei Medicina Interna. Hospital Universitari de Bellvitge.	L'Hospitalet de Llobregat	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Xavier Pinto Sala

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Apo A1 of HDL	The amount of Apo A1 as a marker of HDL composition.	Baseline; 12 weeks	No