Coronary ArteriosclerosisNCT00458055
High-Density Lipoprotein (HDL) Treatment Study
A study testing Atorvastatin; Fenofibrate; Niacin in people with Coronary Arteriosclerosis and Hypoalphalipoproteinemias, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
Trial summary
A low level of plasma high-density lipoprotein (HDL) cholesterol, "the good cholesterol", is the most common lipid abnormality observed in patients with a premature atherosclerotic cardiovascular disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Arteriosclerosis, Hypoalphalipoproteinemias, Genetic Diseases, Inborn
- What is being tested?
- Atorvastatin; Fenofibrate; Niacin
- How many people
- 19 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2006to Sep 2007
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HDL deficiency (HDL-cholesterol < 5th percentile, age and gender-matched)
Who cannot join
- Triglycerides ≥ 5 mmol/L
- Diabetes
- Severe obesity (BMI ≥ 30)
- Alcohol intake > 21 drinks/week
- Untreated disease (thyroid, hepatic or renal)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment Study for Severe High-Density Lipoprotein Deficiency
A low level of plasma high-density lipoprotein (HDL) cholesterol, "the good cholesterol", is the most common lipid abnormality observed in patients with a premature atherosclerotic cardiovascular disease. HDL carry excess cholesterol from peripheral tissues to the liver to be metabolized or excreted, a process known as reverse cholesterol transport.
Epidemiological studies have shown an inverse correlation between plasma levels of HDL cholesterol and the risk of cardiovascular disease. An increase in plasma HDL cholesterol levels by 1 mg/dL may reduce the risk of cardiovascular disease by 2 to 3%. The standard care of treatment for a low level of HDL cholesterol is: 1) lifestyle modifications including exercise, smoking cessation, weight control, moderate alcohol intake and decreased dietary fat intake - all patients are encouraged to follow these lifestyle modifications; 2) medications which can raise HDL cholesterol.
Currently used medications to treat lipid disorders can increase, in some extent, HDL cholesterol. These include niacin (vitamin B3), fibric acid derivatives (fibrates) and statins. However there is no data on the effect of these medications on severe cases of HDL deficiency. This project aims to determine whether currently available medications, used in standard medical practice for the treatment of lipoprotein disorders, can substantially increase HDL cholesterol in severe cases of HDL deficiencies.
Read the detailed description
Objective and rationale. We have collected, in the past 15 years, a large group of patients with familial HDL cholesterol deficiency. In approximately 25% of index probands in our family studies, the genetic basis of HDL deficiency is identified at the molecular level. Approximately 20% of our severe HDL cholesterol deficient patients have mutations within the ABCA1 gene, while mutations at the apoA-I and SMPD1 genes have also been identified. In the present study, we wish to determine whether conventional lipid-regulating medication can substantially increase HDL cholesterol in patients with severe HDL deficiency. Anecdotal reports from our clinic suggest that patients with ABCA1 mutations do not respond to currently available medication; this will be more thoroughly ascertain in this protocol. In addition, examining patients with other genetic HDL deficiencies and familial forms (gene not yet identified) will provide insight on the treatment options for these patients. We feel it is important first whether currently recommended medication can effectively raise HDL cholesterol in these patients.
Study subjects. The subjects will include patients with familial HDL deficiency (HDL cholesterol < 5th percentile for age and gender, with at least one degree relative affected) and HDL deficiency with well-defined genetic mutation. We expect approximately 20-25 patients to enter the study.
Patients will be excluded if at least one of the following criteria is present:
- Triglycerides ≥ 5 mmol/L
- Diabetes
- Severe obesity (BMI ≥ 30)
- Alcohol intake > 21 drinks/week
- Untreated disease (thyroid, hepatic or renal)
Study procedure. Patients will be treated according to current lipid treatment guidelines (McPherson R, Frohlich J, Fodor G, Genest J. Canadian Cardiovascular Society position statement: recommendations for the diagnosis and treatment of dyslipidemias and prevention of cardiovascular disease. Can J Cardiol 2006; 22:913-927) and the use of the three following medications (separately or in combination):
- Lipitor 20 mg
- Lipidil 200 mg
- Niaspan 2 g
It should be noted that all three medications are currently used to treat patients with dyslipidemia and represent the current "standard of care".
Statistics. The null hypothesis expects that no treatment effect increases HDL cholesterol by 10% in the study sample (α = 0.05 and β = 0.8). Using this study design, each patient will serve as his/her own control. Differences between baseline (B) and treatment (T) periods for each medication will be examined by sudent's t-test.
Protocol. Each treatment period will last 8 weeks; wash-out periods will last 4 weeks. Baseline values (B1-3) will be taken at the beginning of each treatment period. On-treatment values (T1-3) will be drawn at the end of each medication period. At each time B (baseline) and T (after a treatment) patient will be examined for:
- Body mass index (weight and height)
- Blood pressure
- Symptoms of ischemic heart disease
- Hepatic functions
- Myopathic symptoms
The following blood test will be performed:
- Total cholesterol
- Triglycerides
- HDL cholesterol
- LDL cholesterol
- ApoA-I, apoB
- ALT, CK
At time B1 blood will also be collected for the determination of:
- TSH
- Creatinine
- ALT
- Blood glucose
In addition, blood will be used to examine the ability of the patient's HDL and plasma to promote cellular cholesterol efflux, using an in vitro model which is well established in our laboratory. Cellular cholesterol efflux tests the efficiency of apoA-I lipidation from cells for the formation of HDL particles. This will provide a general index of the functional status of HDL particles in the body.
- Being tested
- Atorvastatin; Fenofibrate; Niacin
- Keywords
- Lipid lowering agents, Drug treatment, Statin, Fibrate, Niacin, Cellular cholesterol efflux
- Medical subject headings
- Coronary Artery Disease, Hypoalphalipoproteinemias, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atorvastatin; Fenofibrate; NiacinDrug
Also called Lipotor; Tricor; Niaspan
Atorvastatin 20 mg; Fenofibrate 200 mg; Niacin 2g used sequentially for 8 weeks, after 4 weeks washout.
What is being measured
The primary outcome is the main question the study is designed to answer.
HDL cholesterol
Measured: 9 months
Secondary outcomes (1)
apo AI
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2007 (estimated)
- Study startNov 2006
- Primary completionSep 2007
- Study completionSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Coronary ArteriosclerosisStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Sponsor type
- University, hospital or other
- Investigators
- Jacques Genest, MD, Principal investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00458055
- Sponsor's protocol ID
- MUHC-RI 0906
- Status last verified
- Jun 2008
- First submitted
- 5 Apr 2007
- Last updated
- 4 Jun 2008
- Results posted
- No
- Data monitoring committee
- Yes
Publications
McPherson R, Frohlich J, Fodor G, Genest J, Canadian Cardiovascular Society. Canadian Cardiovascular Society position statement--recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease. Can J Cardiol. 2006 Sep;22(11):913-27. doi: 10.1016/s0828-282x(06)70310-5.
PubMed 16971976Brewer HB Jr. High-density lipoproteins: a new potential therapeutic target for the prevention of cardiovascular disease. Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):387-91. doi: 10.1161/01.ATV.0000121505.88326.d2. No abstract available.
PubMed 15003970Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999 Aug 5;341(6):410-8. doi: 10.1056/NEJM199908053410604.
PubMed 10438259Schaefer JR, Schweer H, Ikewaki K, Stracke H, Seyberth HJ, Kaffarnik H, Maisch B, Steinmetz A. Metabolic basis of high density lipoproteins and apolipoprotein A-I increase by HMG-CoA reductase inhibition in healthy subjects and a patient with coronary artery disease. Atherosclerosis. 1999 May;144(1):177-84. doi: 10.1016/s0021-9150(99)00053-2.
PubMed 10381291Ashen MD, Blumenthal RS. Clinical practice. Low HDL cholesterol levels. N Engl J Med. 2005 Sep 22;353(12):1252-60. doi: 10.1056/NEJMcp044370. No abstract available.
PubMed 16177251Schaefer EJ, Asztalos BF. The effects of statins on high-density lipoproteins. Curr Atheroscler Rep. 2006 Jan;8(1):41-9. doi: 10.1007/s11883-006-0063-3.
PubMed 16455013
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Study for Severe High-Density Lipoprotein Deficiency
- ClinicalTrials.gov ID
- NCT00458055
- Acronym / sponsor ID
- MUHC-RI 0906
- Keywords
- Lipid lowering agents, Drug treatment, Statin, Fibrate, Niacin, Cellular cholesterol efflux
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health CentreUniversity, hospital or other
- Study start
- Nov 2006
- Primary completion
- Sep 2007 (actual)
- Study completion
- Sep 2007 (actual)
- First posted
- 9 Apr 2007 (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.
A low level of plasma high-density lipoprotein (HDL) cholesterol, "the good cholesterol", is the most common lipid abnormality observed in patients with a premature atherosclerotic cardiovascular disease. HDL carry excess cholesterol from peripheral tissues to the liver to be metabolized or excreted, a process known as reverse cholesterol transport.
Epidemiological studies have shown an inverse correlation between plasma levels of HDL cholesterol and the risk of cardiovascular disease. An increase in plasma HDL cholesterol levels by 1 mg/dL may reduce the risk of cardiovascular disease by 2 to 3%. The standard care of treatment for a low level of HDL cholesterol is: 1) lifestyle modifications including exercise, smoking cessation, weight control, moderate alcohol intake and decreased dietary fat intake - all patients are encouraged to follow these lifestyle modifications; 2) medications which can raise HDL cholesterol.
Currently used medications to treat lipid disorders can increase, in some extent, HDL cholesterol. These include niacin (vitamin B3), fibric acid derivatives (fibrates) and statins. However there is no data on the effect of these medications on severe cases of HDL deficiency. This project aims to determine whether currently available medications, used in standard medical practice for the treatment of lipoprotein disorders, can substantially increase HDL cholesterol in severe cases of HDL deficiencies.
Detailed description
Objective and rationale. We have collected, in the past 15 years, a large group of patients with familial HDL cholesterol deficiency. In approximately 25% of index probands in our family studies, the genetic basis of HDL deficiency is identified at the molecular level. Approximately 20% of our severe HDL cholesterol deficient patients have mutations within the ABCA1 gene, while mutations at the apoA-I and SMPD1 genes have also been identified. In the present study, we wish to determine whether conventional lipid-regulating medication can substantially increase HDL cholesterol in patients with severe HDL deficiency. Anecdotal reports from our clinic suggest that patients with ABCA1 mutations do not respond to currently available medication; this will be more thoroughly ascertain in this protocol. In addition, examining patients with other genetic HDL deficiencies and familial forms (gene not yet identified) will provide insight on the treatment options for these patients. We feel it is important first whether currently recommended medication can effectively raise HDL cholesterol in these patients.
Study subjects. The subjects will include patients with familial HDL deficiency (HDL cholesterol < 5th percentile for age and gender, with at least one degree relative affected) and HDL deficiency with well-defined genetic mutation. We expect approximately 20-25 patients to enter the study.
Patients will be excluded if at least one of the following criteria is present:
- Triglycerides ≥ 5 mmol/L
- Diabetes
- Severe obesity (BMI ≥ 30)
- Alcohol intake > 21 drinks/week
- Untreated disease (thyroid, hepatic or renal)
Study procedure. Patients will be treated according to current lipid treatment guidelines (McPherson R, Frohlich J, Fodor G, Genest J. Canadian Cardiovascular Society position statement: recommendations for the diagnosis and treatment of dyslipidemias and prevention of cardiovascular disease. Can J Cardiol 2006; 22:913-927) and the use of the three following medications (separately or in combination):
- Lipitor 20 mg
- Lipidil 200 mg
- Niaspan 2 g
It should be noted that all three medications are currently used to treat patients with dyslipidemia and represent the current "standard of care".
Statistics. The null hypothesis expects that no treatment effect increases HDL cholesterol by 10% in the study sample (α = 0.05 and β = 0.8). Using this study design, each patient will serve as his/her own control. Differences between baseline (B) and treatment (T) periods for each medication will be examined by sudent's t-test.
Protocol. Each treatment period will last 8 weeks; wash-out periods will last 4 weeks. Baseline values (B1-3) will be taken at the beginning of each treatment period. On-treatment values (T1-3) will be drawn at the end of each medication period. At each time B (baseline) and T (after a treatment) patient will be examined for:
- Body mass index (weight and height)
- Blood pressure
- Symptoms of ischemic heart disease
- Hepatic functions
- Myopathic symptoms
The following blood test will be performed:
- Total cholesterol
- Triglycerides
- HDL cholesterol
- LDL cholesterol
- ApoA-I, apoB
- ALT, CK
At time B1 blood will also be collected for the determination of:
- TSH
- Creatinine
- ALT
- Blood glucose
In addition, blood will be used to examine the ability of the patient's HDL and plasma to promote cellular cholesterol efflux, using an in vitro model which is well established in our laboratory. Cellular cholesterol efflux tests the efficiency of apoA-I lipidation from cells for the formation of HDL particles. This will provide a general index of the functional status of HDL particles in the body.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- HDL deficiency (HDL-cholesterol < 5th percentile, age and gender-matched)
Key exclusion criteria (5 listed)
- Triglycerides ≥ 5 mmol/L
- Diabetes
- Severe obesity (BMI ≥ 30)
- Alcohol intake > 21 drinks/week
- Untreated disease (thyroid, hepatic or renal)
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 |
|---|---|---|
| Atorvastatin; Fenofibrate; NiacinAlso: Lipotor; Tricor; NiaspanAtorvastatin 20 mg; Fenofibrate 200 mg; Niacin 2g used sequentially for 8 weeks, after 4 weeks washout. | Drug | – |
Primary outcome
HDL cholesterol
Time frame: 9 months
1 secondary outcome
apo AI
Time frame: 9 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2008.
- Background: PubMed 16971976McPherson R, Frohlich J, Fodor G, Genest J, Canadian Cardiovascular Society. Canadian Cardiovascular Society position statement--recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease. Can J Cardiol. 2006 Sep;22(11):913-27. doi: 10.1016/s0828-282x(06)70310-5.
- Background: PubMed 15003970Brewer HB Jr. High-density lipoproteins: a new potential therapeutic target for the prevention of cardiovascular disease. Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):387-91. doi: 10.1161/01.ATV.0000121505.88326.d2. No abstract available.
- Background: PubMed 10438259Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH, Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999 Aug 5;341(6):410-8. doi: 10.1056/NEJM199908053410604.
- Background: PubMed 10381291Schaefer JR, Schweer H, Ikewaki K, Stracke H, Seyberth HJ, Kaffarnik H, Maisch B, Steinmetz A. Metabolic basis of high density lipoproteins and apolipoprotein A-I increase by HMG-CoA reductase inhibition in healthy subjects and a patient with coronary artery disease. Atherosclerosis. 1999 May;144(1):177-84. doi: 10.1016/s0021-9150(99)00053-2.
- Background: PubMed 16177251Ashen MD, Blumenthal RS. Clinical practice. Low HDL cholesterol levels. N Engl J Med. 2005 Sep 22;353(12):1252-60. doi: 10.1056/NEJMcp044370. No abstract available.
- Background: PubMed 16455013Schaefer EJ, Asztalos BF. The effects of statins on high-density lipoproteins. Curr Atheroscler Rep. 2006 Jan;8(1):41-9. doi: 10.1007/s11883-006-0063-3.
- Treatment of high cholesterolLink provided by the sponsor.
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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.
Jacques Genest, MD principal investigator
McGill University Health Centre/Research Institute of the McGill University Health Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Atorvastatin; Fenofibrate; Niacin in people with Coronary Arteriosclerosis and Hypoalphalipoproteinemias, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
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 1 inclusion and 5 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: finished, as of the sponsor's last update on 4 Jun 2008. 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 Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
HDL cholesterol (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00458055, which also lists 6 linked publications.
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 Jun 2008.