Effect of Niacin in the Lipoprotein (a) Concentration

Phase 4

Completed

• Conditions: Hypercholesterolemia
• Interventions: Drug: Niacin/Laropiprant

• Registration Number: NCT01321034
• Lead Sponsor: Instituto Aragones de Ciencias de la Salud

Brief 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.

Detailed 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 ).

Study Timeline

• Study First Submitted: 2011-03-22
• Study First Submitted QC: 2011-03-22
• Study First Posted: 2011-03-23
• Study Start: 2011-10
• Primary Completion: 2012-08
• Study Completion: 2012-12
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-08
• Last Update Posted: 2013-01-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Niacin/Laropiprant	Niacin/Laropiprant	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

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (3)

Hospital San Jorge; 🇪🇸 Huesca, Spain

Hospital Royo Villanova; 🇪🇸 Zaragoza, Spain

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain