Effect of Niacin in the Lipoprotein (a) Concentration

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

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.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Niacin/Laropiprant

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 Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Huesca, Spain
    • Hospital San Jorge
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Zaragoza, Spain
    • Hospital Royo Villanova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: 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	Drug: Niacin/Laropiprant; 1g/20 mg day of Niacin/Laropiprant for 4-weeks followed by 8 additional weeks of 2 g/40 mg day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Instituto Aragones de Ciencias de la Salud
• Collaborators: Hospital Miguel Servet
• Investigators: Principal Investigator: Fernando Civeira, MD, Hospital Miguel Servet

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): December 1, 2012

Study Registration Dates

• First Submitted: March 22, 2011
• First Submitted That Met QC Criteria: March 22, 2011
• First Posted (ESTIMATE): March 23, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): January 10, 2013
• Last Update Submitted That Met QC Criteria: January 8, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Niacin; LPA; Lipoprotein (a); Kringle IV-2 repeats
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Niacin
• Other Study ID Numbers: EudraCT 2010-022258-17