Genetic Basis for Prediction of Non-responders to Dietary Plant Sterol Intervention

NCT02765516 | Terminated

• 1 other identifier: MITACS Converge MC00009
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypercholesterolemia; Cardiovascular Disease

Outcome Measures

Primary Outcomes (1)

• Change in fasting low-density lipoprotein cholesterol (LDL-C) levels between placebo and treatment endpoints (in a crossover design)

  Endpoint (Days 28,29) of each treatment period

Secondary Outcomes (12)

• Change in fasting total cholesterol (TC) levels between placebo and treatment endpoints (in a crossover design)

  Endpoint (Days 28,29) of each treatment period

• Change in fasting high-density lipoprotein cholesterol levels between placebo and treatment endpoints

  Endpoint (Days 28,29) of each treatment period

• Change in fasting triglyceride (TG) levels between placebo and treatment endpoints (in a crossover design)

  Endpoint (Days 28,29) of each treatment period

• Change in body weight between placebo and treatment endpoints (in a crossover design)

  Endpoint (Days 28,29) of each treatment period

• Change in body mass index (BMI) between placebo and treatment endpoints (in a crossover design)

  Endpoint (Days 28,29) of each treatment period

Study Arms (2)

Plant sterols

ACTIVE COMPARATOR

Other: Plant sterols

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

Plant sterols OTHER

2.0g/day of plant sterols incorporated into margarine to be consumed for 28 days

Plant sterols

Placebo OTHER

Identical margarine without additional plant sterols to be consumed for 28 days

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Manitoba: lead
• Mitacs: collaborator
• Unilever R&D: collaborator
• Nutritional Fundamentals for Health: collaborator

Study Sites (1)

Department of Human Nutritional sciences, University of Manitoba

Winnipeg, Manitoba, R3T2N2, Canada

Location

Related Publications (1)

• 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.

  PMID: 32487131 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia; Cardiovascular Diseases

Interventions

Phytosterols

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sterols; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Membrane Lipids; Lipids; Phytochemicals; Biological Factors

Study Officials

• James House, PhD

  University of Manitoba

  PRINCIPAL INVESTIGATOR

• Dylan Mackay, PhD

  University of Manitoba

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head/Professor

Study Record Dates

• First Submitted: April 22, 2016
• First Posted: May 6, 2016
• Study Start: July 5, 2017
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: June 1, 2020

Record last verified: 2020-05

Locations

CA (1)