HyperlipidemiaPhase 2NCT00430430
Lipoprotein Turnover on Low- and High-MUFA Portfolio Diets
A Phase 2 study testing High MUFA dietary portfolio and Low MUFA dietary portfolio in people with Hyperlipidemia and Cardiovascular Diseases, run by University of Toronto at 1 site in Canada.
Trial summary
Low and very low carbohydrate diets, such as the Atkins' Diet, have recently gained attention for their potential health benefits from weight loss and have gained some scientific support from a growing number of studies. Read more about this study
- Who is it for?
- Ages 21 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperlipidemia, Cardiovascular Diseases, Diet Therapy
- What is being tested?
- High MUFA dietary portfolio and Low MUFA dietary portfolio
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2007to Apr 2009
- Phase
- Phase 2
- 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 21 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- men and postmenopausal women
- Body mass index > 18.5 kg/m2 and < 40 kg/m2
- Fasting plasma triglyceride (TG) concentration > 2.5 mmol/l and < 6.0 mmol/l at recruitment.
- Fasting plasma LDL cholesterol concentration > 3.4 mmol/l at recruitment.
- Fasting plasma HDL cholesterol concentration < 1.0 mmol/l at recruitment.
- living within a 40 km radius of St. Michael's Hospital.
Who cannot join
- Premenopausal women will be excluded due to the fluctuation of blood lipids during the menstrual cycle and the difficulty of synchronising the timing of three one month studies with the same point in the menstrual cycle.
- Taking cholesterol medications at the start of the study. However, with their physician's approval those who wish to join but are already taking cholesterol-lowering medications (or cholesterol lowering natural health products) may join the study providing the medications (or natural health products) are stopped for at least 2 weeks before starting the study and throughout the study.
- Patients with uncontrolled high blood pressure will be excluded. The cut off for raised blood pressure has been taken as greater than 140/90mmHg. Patients with systolic blood pressure between 140-150mmHg and diastolic blood pressure between 90-95mmHg may be accepted, since we have found that on the diet their blood pressures tend to be lowered into the acceptable range. For patients in the above normal range (as above), a letter will be required from the physician responsible for their care.
- Changing the type or dose of their drug treatment during the study.
- Those judged as having a likelihood of being non-compliant with instructions for whatever reason. Those with low compliance to lipid-lowering therapy will not be selected.
- Food allergies
Show all 13Show fewer
- Evidence or history of diabetes, renal liver disease or gastrointestinal disease. Patients will be excluded if they have gross xanthoma or advanced premature cardiovascular disease since this group may include hyperabsorbers of plant sterols.
- Patients with major cardiovascular event (stroke or myocardial infarction), with secondary causes of hypercholesterolemia (or untreated hypothyroidism), with uncontrolled blood pressure, major disability or disorder such as liver disease, renal failure or with major surgery < 6 months prior to randomization. Individuals predisposed to hemorrhagic stroke (on the basis of untreated raised blood pressure) will also be excluded.
- Antibiotic use within the last three months.
- Hormone replacement therapy.
- Smokers or have significant alcohol intake (>1 drink/d).
- Disallowed medications will be cholesterol lowering drugs which if prescribed by patients' physicians while on the study will be a reason for discontinuation from the study. Introduction of cholesterol lowering natural health products during the study will also be a reason for withdrawing a participant from the study.
- individuals with acute (<6 weeks) or chronic (>6 weeks) infections, either bacterial or viral, or individuals suffering from chronic inflammatory diseases
Trial locations and contacts
1 site in 1 country.
Canada1 site
Risk Factor Modification Centre, St. Michael's Hospital
Toronto, Ontario, M5C 2T2
About this study
Low and very low carbohydrate diets, such as the Atkins' Diet, have recently gained attention for their potential health benefits from weight loss and have gained some scientific support from a growing number of studies. Benefits have been noted in relation to raised "good" cholesterol, lower "bad" cholesterol and triglycerides. Other studies have shown an advantage in substituting vegetable fat for carbohydrate in insulin resistant individuals and in some instances in type 2 diabetes where improvements were seen in "good" cholesterol and blood sugars. At the same time, our research have been exploring diets containing less processed carbohydrates and other components which in combination (portfolio diet) have a similar cholesterol lowering effect to drug therapy.
Therefore we wish to determine whether our cholesterol-lowering components (portfolio diet) should be incorporated into lower carbohydrate diets especially to preserve "good" cholesterol and lower "bad" cholesterol for decreasing the risk of heart disease.
Read the detailed description
All subjects will undergo two parallel 2-phase treatments. On one treatment, subjects will be placed on a low fat diet for one month (control run-in diet) and then for the second month will continue on the low- fat diet (i.e. low-MUFA) with the addition of the portfolio components. The order of these two phases will not be randomized. The other treatment will be similar to the above except that the background diet of the portfolio phase will be high in monounsaturated fat (high-MUFA). Subjects will be allocated randomly to either treatment. Diets will be metabolically controlled and all food will be provided at weekly intervals.
Subjects will come after a 12h overnight fast to the Risk Factor Modification Center at St. Michael's Hospital or the Department of Nutritional Sciences, University of Toronto immediately prior to commencement of each treatment phase and at weekly intervals during the course of each study period. Prior to the start of the study, subjects will be instructed on details of the study diet protocol. They will also be asked to maintain a constant level of physical activity throughout the course of the study. At all visits, body weight (in kg) will be obtained in indoor clothing, without shoes, and blood pressure will be taken twice in the dominant arm after subjects have been seated for at least 20 minutes. Height (in cm) will be recorded at the first visit. Throughout the study period, subjects will maintain the diet prescribed on their initial visit. At every other visit of each treatment phase, subjects will provide a fasting blood sample. The kinetic tests of lipoprotein metabolism will be performed during the 4th and 8th week of the study. At baseline and during the last week of each study phase, 24h urine collection and 12h breath hydrogen collections will be completed.
The measurement of apolipoprotein in vivo kinetics will be carried out using a primed-constant infusion of [D3]L-leucine. This protocol allows for the determination of the kinetics of all apolipoproteins simultaneously. Kinetics studies will be conducted in the constantly fed state where participants receive 1/30th of their daily energy requirements every half-hour for the whole duration of the test (15 hours). These methods are described in detail in previous publications from our group. Briefly, at 7am on the morning of the study, after a 12-hour overnight fast, participants will be admitted to the Toronto General Hospital Clinical Investigation Unit and two intravenous catheters (IV's) will be inserted, one into each forearm vein. One IV will be for infusion of the stable isotope described below and one for withdrawal of blood samples. After achieving a steady state (3hrs after the small half-hourly meals), subjects will first receive a bolus injection of 10 µmol/kg of body weight of [D3]L-leucine ([D3]L-leucine 98%, C/D/N Isotopes) dissolved in physiological saline (0.9% NaCl) and then a constant infusion of 10 µmol/kg/h of [D3]L-leucine for 12 hours via an intravenous line inserted into a left forearm vein. Blood samples will be collected at regular intervals (0, 1/2, 1, 2, 4, 6, 8, 10, 11, 12hrs). All lipoprotein subfractions will be separated by sequential ultracentrifugation and frozen thereafter at -80oC until they are processed for analysis.
- Conditions
- Hyperlipidemia, Cardiovascular Diseases, Diet Therapy
- Being tested
- High MUFA dietary portfolio, Low MUFA dietary portfolio
- Medical subject headings
- Hyperlipidemias, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High MUFA dietary portfolioProcedure or surgery
high monounsaturated fat background diet to dietary portfolio
Low MUFA dietary portfolioProcedure or surgery
low monounsaturated fat background diet to dietary portfolio
| Study group | Role | What they receive |
|---|---|---|
| High MUFA | Experimental | high monounsaturated fat background diet to portfolio diet Receives: Procedure: High MUFA dietary portfolio |
| Low MUFA | Active comparator | low monounsaturated fat background diet to portfolio diet Receives: Procedure: Low MUFA dietary portfolio |
What is being measured
The primary outcome is the main question the study is designed to answer.
HDL-C and VLDL-TG, synthesis and fractional catabolic rates of their respective apolipoproteins, apo AI and B100
Measured: 2 months
Secondary outcomes (1)
LDL-C, LDL particle size, total and VLDL triglyceride, C-reactive protein, intravascular enzymes, HDL subfractions, blood glucose and insulin (HOMA models S and B), and relation of listed outcomes to kinetic parameters
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2007 (estimated)
- Study startApr 2007
- Primary completionApr 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HyperlipidemiaStudies of the same condition, open and under way.
- More trials run by University of TorontoThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Principal investigator, David Jenkins, University of Toronto
- Investigators
- David JA Jenkins, MD, PhD, DSc, Principal investigator, University of Toronto and St. Michael's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00430430
- Sponsor's protocol ID
- REB 05-120
- Status last verified
- Oct 2016
- First submitted
- 30 Jan 2007
- Last updated
- 27 Oct 2016
- Results posted
- No
Publications
Jenkins DJ, Chiavaroli L, Wong JM, Kendall C, Lewis GF, Vidgen E, Connelly PW, Leiter LA, Josse RG, Lamarche B. Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia. CMAJ. 2010 Dec 14;182(18):1961-7. doi: 10.1503/cmaj.092128. Epub 2010 Nov 1.
PubMed 21041432
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lipoprotein Turnover on Low- and High-MUFA Portfolio Diets
- ClinicalTrials.gov ID
- NCT00430430
- Acronym / sponsor ID
- REB 05-120
- Conditions
- Hyperlipidemia, Cardiovascular Diseases, Diet Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of TorontoUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Apr 2007
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 1 Feb 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.
Low and very low carbohydrate diets, such as the Atkins' Diet, have recently gained attention for their potential health benefits from weight loss and have gained some scientific support from a growing number of studies. Benefits have been noted in relation to raised "good" cholesterol, lower "bad" cholesterol and triglycerides. Other studies have shown an advantage in substituting vegetable fat for carbohydrate in insulin resistant individuals and in some instances in type 2 diabetes where improvements were seen in "good" cholesterol and blood sugars. At the same time, our research have been exploring diets containing less processed carbohydrates and other components which in combination (portfolio diet) have a similar cholesterol lowering effect to drug therapy.
Therefore we wish to determine whether our cholesterol-lowering components (portfolio diet) should be incorporated into lower carbohydrate diets especially to preserve "good" cholesterol and lower "bad" cholesterol for decreasing the risk of heart disease.
Detailed description
All subjects will undergo two parallel 2-phase treatments. On one treatment, subjects will be placed on a low fat diet for one month (control run-in diet) and then for the second month will continue on the low- fat diet (i.e. low-MUFA) with the addition of the portfolio components. The order of these two phases will not be randomized. The other treatment will be similar to the above except that the background diet of the portfolio phase will be high in monounsaturated fat (high-MUFA). Subjects will be allocated randomly to either treatment. Diets will be metabolically controlled and all food will be provided at weekly intervals.
Subjects will come after a 12h overnight fast to the Risk Factor Modification Center at St. Michael's Hospital or the Department of Nutritional Sciences, University of Toronto immediately prior to commencement of each treatment phase and at weekly intervals during the course of each study period. Prior to the start of the study, subjects will be instructed on details of the study diet protocol. They will also be asked to maintain a constant level of physical activity throughout the course of the study. At all visits, body weight (in kg) will be obtained in indoor clothing, without shoes, and blood pressure will be taken twice in the dominant arm after subjects have been seated for at least 20 minutes. Height (in cm) will be recorded at the first visit. Throughout the study period, subjects will maintain the diet prescribed on their initial visit. At every other visit of each treatment phase, subjects will provide a fasting blood sample. The kinetic tests of lipoprotein metabolism will be performed during the 4th and 8th week of the study. At baseline and during the last week of each study phase, 24h urine collection and 12h breath hydrogen collections will be completed.
The measurement of apolipoprotein in vivo kinetics will be carried out using a primed-constant infusion of [D3]L-leucine. This protocol allows for the determination of the kinetics of all apolipoproteins simultaneously. Kinetics studies will be conducted in the constantly fed state where participants receive 1/30th of their daily energy requirements every half-hour for the whole duration of the test (15 hours). These methods are described in detail in previous publications from our group. Briefly, at 7am on the morning of the study, after a 12-hour overnight fast, participants will be admitted to the Toronto General Hospital Clinical Investigation Unit and two intravenous catheters (IV's) will be inserted, one into each forearm vein. One IV will be for infusion of the stable isotope described below and one for withdrawal of blood samples. After achieving a steady state (3hrs after the small half-hourly meals), subjects will first receive a bolus injection of 10 µmol/kg of body weight of [D3]L-leucine ([D3]L-leucine 98%, C/D/N Isotopes) dissolved in physiological saline (0.9% NaCl) and then a constant infusion of 10 µmol/kg/h of [D3]L-leucine for 12 hours via an intravenous line inserted into a left forearm vein. Blood samples will be collected at regular intervals (0, 1/2, 1, 2, 4, 6, 8, 10, 11, 12hrs). All lipoprotein subfractions will be separated by sequential ultracentrifugation and frozen thereafter at -80oC until they are processed for analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High MUFA | Experimental | Procedure: High MUFA dietary portfoliohigh monounsaturated fat background diet to portfolio diet |
| Low MUFA | Active comparator | Procedure: Low MUFA dietary portfoliolow monounsaturated fat background diet to portfolio diet |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- men and postmenopausal women
- Body mass index > 18.5 kg/m2 and < 40 kg/m2
- Fasting plasma triglyceride (TG) concentration > 2.5 mmol/l and < 6.0 mmol/l at recruitment.
- Fasting plasma LDL cholesterol concentration > 3.4 mmol/l at recruitment.
- Fasting plasma HDL cholesterol concentration < 1.0 mmol/l at recruitment.
Key exclusion criteria (13 listed)
- Premenopausal women will be excluded due to the fluctuation of blood lipids during the menstrual cycle and the difficulty of synchronising the timing of three one month studies with the same point in the menstrual cycle.
- Taking cholesterol medications at the start of the study. However, with their physician's approval those who wish to join but are already taking cholesterol-lowering medications (or cholesterol lowering natural health products) may join the study providing the medications (or natural health products) are stopped for at least 2 weeks before starting the study and throughout the study.
- Patients with uncontrolled high blood pressure will be excluded. The cut off for raised blood pressure has been taken as greater than 140/90mmHg. Patients with systolic blood pressure between 140-150mmHg and diastolic blood pressure between 90-95mmHg may be accepted, since we have found that on the diet their blood pressures tend to be lowered into the acceptable range. For patients in the above normal range (as above), a letter will be required from the physician responsible for their care.
- Changing the type or dose of their drug treatment during the study.
- Those judged as having a likelihood of being non-compliant with instructions for whatever reason. Those with low compliance to lipid-lowering therapy will not be selected.
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 |
|---|---|---|
| High MUFA dietary portfoliohigh monounsaturated fat background diet to dietary portfolio | Procedure or surgery | High MUFA |
| Low MUFA dietary portfoliolow monounsaturated fat background diet to dietary portfolio | Procedure or surgery | Low MUFA |
Primary outcome
HDL-C and VLDL-TG, synthesis and fractional catabolic rates of their respective apolipoproteins, apo AI and B100
Time frame: 2 months
1 secondary outcome
LDL-C, LDL particle size, total and VLDL triglyceride, C-reactive protein, intravascular enzymes, HDL subfractions, blood glucose and insulin (HOMA models S and B), and relation of listed outcomes to kinetic parameters
Time frame: 2 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 27 Oct 2016.
- Derived from this study: PubMed 21041432Jenkins DJ, Chiavaroli L, Wong JM, Kendall C, Lewis GF, Vidgen E, Connelly PW, Leiter LA, Josse RG, Lamarche B. Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia. CMAJ. 2010 Dec 14;182(18):1961-7. doi: 10.1503/cmaj.092128. Epub 2010 Nov 1.
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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.
David JA Jenkins, MD, PhD, DSc principal investigator
University of Toronto and St. Michael's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing High MUFA dietary portfolio and Low MUFA dietary portfolio in people with Hyperlipidemia and Cardiovascular Diseases, run by University of Toronto 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 6 inclusion and 13 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 27 Oct 2016. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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-C and VLDL-TG, synthesis and fractional catabolic rates of their respective apolipoproteins, apo AI and B100 (time frame: 2 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 NCT00430430, which also lists 1 linked publication.
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 27 Oct 2016.