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Lipoprotein Turnover on Low- and High-MUFA Portfolio Diets

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ClinicalTrials.gov Identifier: NCT00430430
Recruitment Status : Completed
First Posted : February 1, 2007
Last Update Posted : October 27, 2016
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
David Jenkins, University of Toronto

Tracking Information
First Submitted Date  ICMJE January 30, 2007
First Posted Date  ICMJE February 1, 2007
Last Update Posted Date October 27, 2016
Study Start Date  ICMJE April 2007
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2016)
HDL-C and VLDL-TG, synthesis and fractional catabolic rates of their respective apolipoproteins, apo AI and B100 [ Time Frame: 2 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 30, 2007)
HDL-C and VLDL-TG, synthesis and fractional catabolic rates of their respective apolipoproteins, apo AI and B100
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2016)
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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2007)
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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lipoprotein Turnover on Low- and High-MUFA Portfolio Diets
Official Title  ICMJE Lipoprotein Turnover on Low- and High-MUFA Portfolio Diets
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Hyperlipidemia
  • Cardiovascular Diseases
  • Diet Therapy
Intervention  ICMJE
  • Procedure: High MUFA dietary portfolio
    high monounsaturated fat background diet to dietary portfolio
  • Procedure: Low MUFA dietary portfolio
    low monounsaturated fat background diet to dietary portfolio
Study Arms  ICMJE
  • Experimental: High MUFA
    high monounsaturated fat background diet to portfolio diet
    Intervention: Procedure: High MUFA dietary portfolio
  • Active Comparator: Low MUFA
    low monounsaturated fat background diet to portfolio diet
    Intervention: Procedure: Low MUFA dietary portfolio
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 30, 2007)
24
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2009
Actual Primary Completion Date April 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00430430
Other Study ID Numbers  ICMJE REB 05-120
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party David Jenkins, University of Toronto
Study Sponsor  ICMJE University of Toronto
Collaborators  ICMJE Canadian Institutes of Health Research (CIHR)
Investigators  ICMJE
Principal Investigator: David JA Jenkins, MD, PhD, DSc University of Toronto and St. Michael's Hospital
PRS Account University of Toronto
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP