Effect of Niacin in the Lipoprotein (a) Concentration

Hypercholesterolemia Clinical Trial

Official title:

Effect of Niacin in the Lipoprotein (a) Concentration With Regard to Apolipoprotein (a) Size and Baseline Lipoprotein (a) Concentration.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01321034
• Other study ID #: EudraCT 2010-022258-17
• Status: Completed
• Phase: Phase 4
• First received: March 22, 2011
• Last updated: January 8, 2013
• Start date: October 2011
• Est. completion date: December 2012

Study information

• Verified date: January 2013
• Source: Instituto Aragones de Ciencias de la Salud
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Sudirección General de Medicamentos de Uso Humano
• Study type: Interventional

Clinical Trial Summary

Objectives.

• To evaluate the absolute and relative Lp(a) lowering effect of 1g/20 mg and 2 g/40 mg day of Niacin/Laropiprant in subjects with normal Lp(a) (< 30 mg/dL), high Lp(a) (30-60 mg/dL) and very high Lp(a) (> 60 mg/dL).

• To evaluate the absolute and relative Lp(a) lowering effect of 1g/20 mg and 2 g/40 mg day of Niacin/Laropiprant depending on the number of kringle IV-2 repeated copies on the apo(a) gene. 2.1.1 Hypotheses.

• The Lp(a) lowering effect of niacin is dependent of the pre-treatment Lp(a) concentration, with higher absolute and relative reduction in Lp(a) in subjects with hyperlipoproteinemia(a).

• Lp(a) size, throughout modifying hepatic synthesis of apo(a), is a major factor related to the lowering effect variability of niacin in human.

Description:

Open-label 12-week study, 1g/20 mg day of Niacin/Laropiprant for 4-weeks followed by 8 additional weeks of 2 g/40 mg day. Subjects with normal Lp(a) will be use as comparative group for the other two groups, so no placebo group is required is this study.

Subjects: volunteers from the Lipid Clinic of Hospital Universitario Miguel Servet of Zaragoza, Spain. Subjects were selected according to their previously determined Lp(a)concentration. All volunteers before any study procedure will have to give written inform consent to a protocol previously approved for the Ethical Committees of our institutions.

Biochemical determinations: lipids: total cholesterol and triglycerides; lipoproteins:

HDL-cholesterol, Lp(a); apolipoproteins: Apo A1 and apo B and safety biochemical parameters (glucose, uric acid, creatinine, liver and muscle enzymes will be measured at baseline and at the end of the two treatment periods (weeks 4 and 8).

An adverse experience questionnaire will be done in each visit. Genetic analysis: apo(a) genetic polymorphism responsible of the Lp(a) size variability will be analyzed by a PCR-based methodology (Lanktree et al. J Lipid Res 2009; 50: 768-72 ).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: December 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Age >18 and < 80 years

2. LDL cholesterol between 70 and 190 mg/dL

3. Triglycerides < 500 mg/dL

4. At least 2 Lp(a) determinations previous to the beginning of the study without differences >20% or > 20 mg/dL.

5. No lipid lowering therapy or on stable doses in the last 3 months

Exclusion Criteria:

1. Liver disease or liver enzymes >2 times higher than reference values

2. Creatinine > 2 mg/dL

3. Active peptic ulcer

4. Clinical gout in the last year

5. Uncontrolled diabetes (HbA1c >8%)

6. Enrolment in other drug clinical trial in the previous 3 months.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• Niacin/Laropiprant
1g/20 mg day of Niacin/Laropiprant for 4-weeks followed by 8 additional weeks of 2 g/40 mg day.

Locations

Country	Name	City	State
Spain	Hospital San Jorge	Huesca
Spain	Hospital Royo Villanova	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Aragones de Ciencias de la Salud	Hospital Miguel Servet

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	absolute and relative Lp(a) lowering effect of 1g/20 mg and 2 g/40 mg day of Niacin/Laropiprant in subjects with normal Lp(a) (<30 mg/dL), high Lp(a) (30-60 mg/dL) and very high Lp(a) (>60 mg/dL g/40 mg day of Niacin/Laropiprant		8 weeks	No
Secondary	absolute and relative Lp(a) lowering effect of 1g/20 mg and 2 g/40 mg day of Niacin/Laropiprant depending on the number of kringle IV-2 repeated copies on the apo(a) gene.		8 weeks	No