Elevated Lipoprotein(a) LevelsPhase 3NICOLaNCT00633698
Evaluation of the Effect of NICOtinic Acid (Niacin) on Elevated Lipoprotein(a) Levels (NICOLa Study)
A Phase 3 study testing Nicotinic acid (niacin) in people with Elevated Lipoprotein(a) Levels, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Elevated Lipoprotein(a) Levels
- What is being tested?
- Nicotinic acid (niacin)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2008to Mar 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 28Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Institute of Social Medicine, Epidemiology and Health Economics
Berlin, State of Berlin, 10098
About this study
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).
Read the detailed description
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.
Subjects will be assessed at week -4 (run-in / wash-out), 0a+b (screening phase), 1, 5, 9, 13, and 20. Descriptive statistics will be used to summarize continuous and categorical variables. Mean change of Lp(a) levels will be compared between treatment and placebo group. Subjects will be grouped according to treatment randomised (intention-to-treat, ITT population). For missing data, the last observation will be carried forward (LOCF). Comparisons between groups will be performed using analysis of covariance (ANCOVA) with treatment as a factor, adjusting for baseline Lp(a) levels and other potential confounders.
Subgroup analyses will be performed according to Lp(a) phenotype, Lp(a) baseline level ( > 30-60 mg/dl, > 60 mg/dl), and concurrent statin therapy (yes / no).
Risks:
Flushing is the most common side effect of niacin. Other side effects include gastrointestinal disorders (common) (diarrhoea, nausea, vomiting, abdominal pain, or dyspepsia) and cardiac disorders (uncommon) (tachycardia, palpitations). A reversible elevation of liver enzymes has been reported, as well as a decreased glucose tolerance, reductions in platelet counts, increases in prothrombin time, elevations in uric acid levels, and reductions in phosphorous levels (uncommon or rarely). Hypersensitivity reactions have been reported very rarely.
Single reports on rhabdomyolysis in patients on combined therapy with niacin and HMG-CoA reductase inhibitors (statins) have been reported. Careful monitoring for any signs and symptoms of myopathy such as muscle pain, tenderness, or weakness is therefore required in the case of combination therapy.
Benefit:
Niacin has been shown to improve the lipid profile in patients with reductions in total cholesterol, LDL cholesterol and triglycerides and increases in HDL cholesterol. Niacin may also reduce elevated Lp(a) levels and may thus lower cardiovascular events in the long term.
The following variables will be assessed prior randomisation: socio-demographic factors, physical examinations, medical history, concurrent medication, health-related quality of life, costs prior study entry, and lipid as well as other laboratory parameters. Lipid parameters include Lp(a), total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides.
At follow-up, the respective laboratory analyses and physical examinations will be assessed at each visit. Subjects will be investigated with regard to safety and tolerability. Health-related quality of life and costs will be assessed at week 9 and 20.
- Conditions
- Elevated Lipoprotein(a) Levels
- Being tested
- Nicotinic acid (niacin), Placebo
- Keywords
- lipoprotein(a), niacin, placebo, intervention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotinic acid (niacin)Drug
Also called Niaspan
oral medication Week 1-4: 500 mg per day Week 5-8: 1000 mg per day Week 9-12: 1500 mg per day Week 13-20: 2000 mg per day
PlaceboDrug
Placebo Week 1-4: 500 mg per day Week 5-8: 1000 mg per day Week 9-12: 1500 mg per day Week 13-20: 2000 mg per day
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Nicotinic acid (niacin) Receives: Drug: Nicotinic acid (niacin) |
| 2 | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change in Lp(a) levels
Measured: 20 weeks
Secondary outcomes (11)
Mean change in total cholesterol levels
Measured: 20 weeks
Mean change in LDL (low density lipoprotein) cholesterol levels
Measured: 20 weeks
Mean change in HDL (high density lipoprotein) cholesterol levels
Measured: 20 weeks
Mean change in triglyceride levels
Measured: 20 weeks
Mean change in blood glucose levels
Measured: 20 weeks
Health-related quality of life
Measured: 20 weeks
Disease-related costs
Measured: 20 weeks
Clinical adverse events
Measured: 20 weeks
Laboratory safety parameters
Measured: 20 weeks
Adherence to medication
Measured: 20 weeks
Tolerability of medication
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2008 (estimated)
- Study startJan 2008
- Primary completionDec 2009 (estimated)
- Study completionMar 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Elevated Lipoprotein(a) LevelsStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Investigators
- Elisabeth Steinhagen-Thiessen, MD, Study director, Lipidambulanz und Lipidapherese, Charité Campus Virchow-Klinikum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00633698
- Sponsor's protocol ID
- Ep_Li 001_2006
- Other IDs
- EudraCT No.: 2006-005710-12
- Acronym
- NICOLa
- Status last verified
- Aug 2009
- First submitted
- 5 Mar 2008
- Last updated
- 4 Aug 2009
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effect of NICOtinic Acid (Niacin) on Elevated Lipoprotein(a) Levels (NICOLa Study)
- ClinicalTrials.gov ID
- NCT00633698
- Acronym / sponsor ID
- NICOLa / Ep_Li 001_2006
- Conditions
- Elevated Lipoprotein(a) Levels
- Keywords
- lipoprotein(a), niacin, placebo, intervention
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- Dec 2009 (estimated)
- Study completion
- Mar 2010 (estimated)
- First posted
- 12 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Subjects will be assessed at week -4 (run-in / wash-out), 0a+b (screening phase), 1, 5, 9, 13, and 20. Descriptive statistics will be used to summarize continuous and categorical variables. Mean change of Lp(a) levels will be compared between treatment and placebo group. Subjects will be grouped according to treatment randomised (intention-to-treat, ITT population). For missing data, the last observation will be carried forward (LOCF). Comparisons between groups will be performed using analysis of covariance (ANCOVA) with treatment as a factor, adjusting for baseline Lp(a) levels and other potential confounders.
Subgroup analyses will be performed according to Lp(a) phenotype, Lp(a) baseline level ( > 30-60 mg/dl, > 60 mg/dl), and concurrent statin therapy (yes / no).
Risks:
Flushing is the most common side effect of niacin. Other side effects include gastrointestinal disorders (common) (diarrhoea, nausea, vomiting, abdominal pain, or dyspepsia) and cardiac disorders (uncommon) (tachycardia, palpitations). A reversible elevation of liver enzymes has been reported, as well as a decreased glucose tolerance, reductions in platelet counts, increases in prothrombin time, elevations in uric acid levels, and reductions in phosphorous levels (uncommon or rarely). Hypersensitivity reactions have been reported very rarely.
Single reports on rhabdomyolysis in patients on combined therapy with niacin and HMG-CoA reductase inhibitors (statins) have been reported. Careful monitoring for any signs and symptoms of myopathy such as muscle pain, tenderness, or weakness is therefore required in the case of combination therapy.
Benefit:
Niacin has been shown to improve the lipid profile in patients with reductions in total cholesterol, LDL cholesterol and triglycerides and increases in HDL cholesterol. Niacin may also reduce elevated Lp(a) levels and may thus lower cardiovascular events in the long term.
The following variables will be assessed prior randomisation: socio-demographic factors, physical examinations, medical history, concurrent medication, health-related quality of life, costs prior study entry, and lipid as well as other laboratory parameters. Lipid parameters include Lp(a), total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides.
At follow-up, the respective laboratory analyses and physical examinations will be assessed at each visit. Subjects will be investigated with regard to safety and tolerability. Health-related quality of life and costs will be assessed at week 9 and 20.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Nicotinic acid (niacin)Nicotinic acid (niacin) |
| 2 | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (28 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nicotinic acid (niacin)Also: Niaspanoral medication Week 1-4: 500 mg per day Week 5-8: 1000 mg per day Week 9-12: 1500 mg per day Week 13-20: 2000 mg per day | Drug | 1 |
| PlaceboPlacebo Week 1-4: 500 mg per day Week 5-8: 1000 mg per day Week 9-12: 1500 mg per day Week 13-20: 2000 mg per day | Drug | 2 |
Primary outcome
Mean change in Lp(a) levels
Time frame: 20 weeks
11 secondary outcomes
Mean change in total cholesterol levels
Time frame: 20 weeks
Mean change in LDL (low density lipoprotein) cholesterol levels
Time frame: 20 weeks
Mean change in HDL (high density lipoprotein) cholesterol levels
Time frame: 20 weeks
Mean change in triglyceride levels
Time frame: 20 weeks
Mean change in blood glucose levels
Time frame: 20 weeks
Health-related quality of life
Time frame: 20 weeks
Disease-related costs
Time frame: 20 weeks
Clinical adverse events
Time frame: 20 weeks
Laboratory safety parameters
Time frame: 20 weeks
Adherence to medication
Time frame: 20 weeks
Tolerability of medication
Time frame: 20 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elisabeth Steinhagen-Thiessen, MD study director
Lipidambulanz und Lipidapherese, Charité Campus Virchow-Klinikum
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nicotinic acid (niacin) in people with Elevated Lipoprotein(a) Levels, run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Aug 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean change in Lp(a) levels (time frame: 20 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2009.