Clinical trial NCT01321034: Effect of Niacin in the Lipoprotein (a) Concentration
Official title: Effect of Niacin in the Lipoprotein (a) Concentration With Regard to Apolipoprotein (a) Size and Baseline Lipoprotein (a) Concentration.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypercholesterolemia
Keywords: Lipoprotein (a)
LPA
Niacin
Kringle IV-2 repeats
Lead sponsor: Instituto Aragones de Ciencias de la Salud
Sponsor class: OTHER_GOV
Collaborators: name: Hospital Miguel Servet
First posted: 2011-03-23
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 ).

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 8 weeks
Secondary outcomes:
measure: 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.
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Huesca
country: Spain
facility: Hospital San Jorge
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Zaragoza
country: Spain
facility: Hospital Royo Villanova
Study officials:
affiliation: Hospital Miguel Servet
name: Fernando Civeira, MD
role: PRINCIPAL_INVESTIGATOR
References: