Evaluation of the Effect of NICOtinic Acid (Niacin) on Elevated Lipoprotein(a) Levels (NICOLa Study)
试验速览
- 阶段
- 3 期
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Mean change in Lp(a) levels
研究概览
简要总结
Lipoprotein (Lp)(a) has been associated with increased risk of cardiovascular disease. Niacin has been shown to lower Lp(a) in patients with normal or moderately elevated levels. However, there are few studies assessing the effectiveness of niacin in Lp(a) levels above 30 mg/dl. In addition, most studies investigating the effectiveness of niacin have only included small numbers of patients. Also, Lp(a) was only assessed as a secondary endpoint. The aim of the present study was, therefore, to evaluate whether Niacin is effective compared to placebo in the reduction of an elevated Lp(a).
详细描述
The study is a randomised, multicentre, placebo-controlled, 2-arm, parallel group, phase III, intervention study. Following randomisation at visit 1, subjects will receive 20 weeks of treatment with niacin or placebo.
The research question is: niacin therapy effective in lowering elevated Lipoprotein (Lp)(a) levels in comparison to placebo?
Sample size calculation is based on the t test of equal means with unequal group size (ratio: treatment group / control group = 2:1). The significance level is α=0.05 and the power 90%. Assuming a drop-out rate of 20%, sample size is 100 in the niacin group and 50 in the placebo group.
The active ingredient in the modified (prolonged, extended) release tablets is nicotinic acid, a B-complex vitamin. Modified release tablets containing 500 mg nicotinic acid, once daily for oral use, will be used.te of 20%, sample size is 100 in the niacin group and 50 in the placebo group.
Subjects will be recruited consecutively in the participating lipid clinics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects, aged 18 - 75 years
- •Subjects with and without cardiovascular diseases
- •Lp(a) plasma levels > 30 mg/dl
- •Triglyceride levels < 400 mg/dl
- •Cholesterol and triglyceride levels not requiring immediate change in medication according to current clinical guidelines
- •If concurrent statin therapy, stable doses are required in the four weeks prior study inclusion, and no changes in statin dosages are allowed during the study period
- •Subjects willing to follow all study procedures including attendance at practices for scheduled study visits, fasting prior to blood draws and compliance with study treatment regimen
- •Written informed consent to participate in the trial
排除标准
- •Known hypertriglyceridaemia or fasting triglycerides >= 400 mg/dl in the last four weeks before the randomisation visit.
- •Known heterozygous or homozygous familial hypercholesterolaemia or known type III hyperlipoproteinaemia (familial dysbetalipoproteinaemia)
- •Documented secondary hypercholesterolaemia of any cause
- •Initiation of a lipid-modifying drug treatment or a dose change of a lipid-modifying drug within the last four weeks
- •Known hypersensitivity to nicotinic acid or any component of this medication or their derivatives
- •Concurrent treatment with products containing significant amounts (more than 100 mg as daily dose) of nicotinic acid (niacin) or nicotinamide (e.g., vitamin preparations and nutritional supplements)
- •Concurrent treatment with an immediate release formulation of nicotinic acid or a nicotinic acid analogue, e.g. supplements
- •Treatment with an anticoagulant such as marcumar
- •Cardiovascular diseases which are contra-indicated: unstable angina, acute myocardial infarction or uncontrolled cardiac arrhythmias within the preceding 3 months, stroke within the preceding 6 months, symptomatic heart failure (NYHA class III or IV), or severe peripheral artery disease
- •Pregnant women, women who are breast feeding, and women of childbearing potential who are not using chemical or mechanical contraception (prescription oral contraceptives, abstinence, condoms with spermicide, surgical sterilisation, diaphragm with spermicide, or intrauterine device)
- •History of malignancy, except subjects who have been disease free for more than 10 years or whose only malignancy has been basal or squamous cell skin carcinoma. Women with a history of cervical dysplasia should be excluded unless 3 consecutive normal cervical smears have subsequently been recorded before entry into the study.
- •History of alcohol (more than 2 glasses of wine or alcohol equivalent per day) or drug abuse (within 12 months of screening), or both
- •Active liver disease or hepatic dysfunction as defined by elevations of AST or ALT >=1.5 times the ULN in the last 4 weeks before the randomisation visit
- •Known uncontrolled or poorly controlled (HbA1C > 9 %) diabetes
- •Persistent uncontrolled or untreated hypertension, defined as either resting diastolic blood pressure of > 95 mmHg or resting systolic blood pressure of > 200 mmHg
- •Unexplained serum creatine phosphokinase (CK) > 3 times the ULN in the last 4 weeks before the randomisation visit (e.g. not due to recent trauma, intramuscular injections, heavy exercise etc)
- •History of severe myalgia of unknown origin
- •Arterial bleeding
- •Active peptic ulcer
- •Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins
- •Active gout symptoms
- •Significant renal insufficiency (serum creatinine > 1.5 mg/dl)
- •Planned hospitalizations for diagnostic or surgical procedures within the next 5 months
- •Known infectious disease such as hepatitis or HIV
- •Participation in another investigational drug trial within the four weeks prior to study entry
- •Previous randomisation into this study
- •Subjects with serious or unstable medical or psychological condition that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study.
- •Persons who are detained officially or legally to an official institution.
研究组 & 干预措施
1
Nicotinic acid (niacin)
干预措施: Nicotinic acid (niacin) (Drug)
2
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Mean change in Lp(a) levels
时间窗: 20 weeks
次要结局
- Mean change in total cholesterol levels(20 weeks)
- Mean change in LDL (low density lipoprotein) cholesterol levels(20 weeks)
- Mean change in HDL (high density lipoprotein) cholesterol levels(20 weeks)
- Mean change in triglyceride levels(20 weeks)
- Mean change in blood glucose levels(20 weeks)
- Health-related quality of life(20 weeks)
- Disease-related costs(20 weeks)
- Clinical adverse events(20 weeks)
- Laboratory safety parameters(20 weeks)
- Adherence to medication(20 weeks)
- Tolerability of medication(20 weeks)