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Genetic Basis for Prediction of Non-responders to Dietary Plant Sterol Intervention (GenePredict-PS)

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ClinicalTrials.gov Identifier: NCT02765516
Recruitment Status : Terminated (Inability to recruit)
First Posted : May 6, 2016
Last Update Posted : June 1, 2020
Sponsor:
Collaborators:
Mitacs
Unilever R&D
Nutritional Fundamentals for Health
Information provided by (Responsible Party):
Dr. J. House, University of Manitoba

Tracking Information
First Submitted Date  ICMJE April 22, 2016
First Posted Date  ICMJE May 6, 2016
Last Update Posted Date June 1, 2020
Actual Study Start Date  ICMJE July 5, 2017
Actual Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 4, 2016)
Change in fasting low-density lipoprotein cholesterol (LDL-C) levels between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2017)
  • Change in fasting total cholesterol (TC) levels between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in fasting high-density lipoprotein cholesterol levels between placebo and treatment endpoints [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in fasting triglyceride (TG) levels between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in body weight between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in body mass index (BMI) between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in waist circumference between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in blood pressure between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in arterial stiffness-Pulse wave velocity between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
    Pulse wave velocity will be determined using an automated oscillometric measurement device (Mobil-O-Graph, IEM, Stolberg, Germany).
  • Change in arterial stiffness-augmentation index between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
    Augmentation index will be determined using an automated oscillometric measurement device (Mobil-O-Graph, IEM, Stolberg, Germany).
  • Change in fasting glucose levels between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in blood sterols and sterol precursors (non-cholesterol sterols) levels between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in fractional cholesterol synthesis between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Day 28,29) of each treatment period ]
    A fasted blood sample will be taken on day 28 of each study period prior to deuterium oxide administration, as well as fasting samples on day 29. The change in deuterium enrichment within red blood cell (RBC) free cholesterol we be determined as an index of synthesis over days 28 and 29.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 4, 2016)
  • Change in fasting total cholesterol (TC) levels between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in fasting high-density lipoprotein cholesterol levels between placebo and treatment endpoints [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in fasting triglyceride (TG) levels between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in body weight between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in body mass index (BMI) between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in height between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in waist circumference between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in blood pressure between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in arterial stiffness-Pulse wave velocity between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
    Pulse wave velocity will be determined using an automated oscillometric measurement device (Mobil-O-Graph, IEM, Stolberg, Germany).
  • Change in arterial stiffness-augmentation index between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
    Augmentation index will be determined using an automated oscillometric measurement device (Mobil-O-Graph, IEM, Stolberg, Germany).
  • Change in fasting glucose levels between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in blood sterols and sterol precursors (non-cholesterol sterols) levels between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Days 28,29) of each treatment period ]
  • Change in fractional cholesterol synthesis between placebo and treatment endpoints (in a crossover design) [ Time Frame: Endpoint (Day 28,29) of each treatment period ]
    A fasted blood sample will be taken on day 28 of each study period prior to deuterium oxide administration, as well as fasting samples on day 29. The change in deuterium enrichment within red blood cell (RBC) free cholesterol we be determined as an index of synthesis over days 28 and 29.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Genetic Basis for Prediction of Non-responders to Dietary Plant Sterol Intervention
Official Title  ICMJE Genetic Basis for Prediction of Non-responders to Dietary Plant Sterol Intervention
Brief Summary The objective of this study is to utilize information on associations between genetic predisposition pertaining to multiple single nucleotide polymorphisms (SNPs) and the degree of responsiveness of low-density lipoprotein cholesterol (LDL-C) lowering to plant sterols (PS). The predictive potential of SNPs associated with PS responsiveness will be evaluated using a randomized human intervention trial examining responsiveness of lowering blood LDL-C levels to PS intervention.
Detailed Description On average plant sterol (PS) consumption of 2-3 grams a day leads to a ~10% decrease in low-density lipoprotein cholesterol (LDL-C). However, inter-individual response to PS consumption varies, with some individuals showing low or no reductions in LDL-C levels, while some even showing an increase in levels. Determining factors that predict the direction of response of LDL-C to PS would be helpful in identifying individuals who should consume PS and individuals who should seek another method of treating hypercholesterolemia. The objective of this research proposal is to test the a priori predictive potential of a combination of three single nucleotide polymorphisms (SNPs), i.e., genosets, previously associated with response to PS in a post-hoc manner. A clinical trial with a priori recruitment of participants based on genoset which will test LDL-C response to PS consumption using a randomized, double blind, placebo controlled crossover design is proposed.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Hypercholesterolemia
  • Cardiovascular Disease
Intervention  ICMJE
  • Other: Plant sterols
    2.0g/day of plant sterols incorporated into margarine to be consumed for 28 days
  • Other: Placebo
    Identical margarine without additional plant sterols to be consumed for 28 days
Study Arms  ICMJE
  • Active Comparator: Plant sterols
    Intervention: Other: Plant sterols
  • Placebo Comparator: Placebo
    Intervention: Other: Placebo
Publications * Shamloo M, Granger MJ, Trautwein EA, House JD, MacKay D. Genetic basis for prediction of non-responders to dietary plant sterol intervention (GenePredict-PS): a study protocol for a double-blind, placebo-controlled, randomized two-period crossover study. Trials. 2020 Jun 1;21(1):452. doi: 10.1186/s13063-020-04364-5.

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: September 24, 2019)
43
Original Estimated Enrollment  ICMJE
 (submitted: May 4, 2016)
64
Actual Study Completion Date  ICMJE December 31, 2019
Actual Primary Completion Date December 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Fasting LDL-C concentration >3.0 and <4.9 mmol/L
  • Fasting glucose concentration <6.1 mmol/L
  • Fasting triglyceride concentration <4.52 mmol/L
  • Genoset required: ; ApoE ε3/ε3 CYP7A1 rs3808607 T/T (n=20); ApoE ε3/ε3 CYP7A1 rs3808607 G/- (n=22); ApoE ε4/- CYP7A1 rs3808607 -/- (n=22)

Exclusion Criteria:

  • Consuming, or have consumed in the last 3 months, medications or nutritional supplements which are known to affect lipid metabolism (such as cholestyramine, colestipol, niacin, clofibrate, gemfibrozil, probucol, HMG-CoA R inhibitors, methotrexate, high dose dietary supplements, fish oil capsules or plant sterol or stanol), or have any dietary restrictions which would prevent them from consuming the trial treatments
  • BMI >40
  • Must not have self-reported weight gain or loss greater than 3 kg in the past three months
  • Phytosterolemic
  • History of active cardiovascular disease including stroke, congestive heart failure, myocardial infarction, unstable angina pectoris, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, temporal ischemic attacks, anemia, abnormal electrolytes, proteinuria, and abnormal liver, kidney or thyroid function
  • Type 1 or type 2 diabetes, a history of cancer or malignancy in the last 5 years, or any metabolic disease, gastrointestinal disorder or other clinically significant disease/disorder which could interfere with the results of the study or the safety of the participant.
  • Uncontrolled hypertension having systolic blood pressure >160mm Hg or diastolic blood pressure >100mm Hg
  • Smoker, tobacco/snuff/nicotine users, recreational drug users
  • Consume more than 14 alcoholic beverages a week
  • Participants who are pregnant or plan to become pregnant during the trial period or lactating mothers
  • Participants will be excluded if they have clinically significant biochemistry defined as: LDL-C <3.0mmol/L or >4.9 mmol/L; TC > 6.2 mmol/L; fasting glucose: > 6.1 mmol/ l, fasting TG >4.52 mmol/L; AST >100 U/L; ALT >100 U/L or or any other clinically significant abnormality in hematology and/or biochemistry at the investigator's discretion
  • Patients with unstable or serious illness, for example, dementia, terminal illness, recent bereavement, recent significant medical diagnosis will also be excluded
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 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 NCT02765516
Other Study ID Numbers  ICMJE MITACS Converge MC00009
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Dr. J. House, University of Manitoba
Study Sponsor  ICMJE University of Manitoba
Collaborators  ICMJE
  • Mitacs
  • Unilever R&D
  • Nutritional Fundamentals for Health
Investigators  ICMJE
Principal Investigator: James House, PhD University of Manitoba
Principal Investigator: Dylan Mackay, PhD University of Manitoba
PRS Account University of Manitoba
Verification Date May 2020

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