Back to results

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

Primary Purpose

Hypercholesterolemia, Cardiovascular Disease

Status

Terminated

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Plant sterols

Placebo

About this trial

This is an interventional prevention trial for Hypercholesterolemia

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Department of Human Nutritional sciences, University of Manitoba

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Plant sterols

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

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

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

Change in waist circumference between placebo and treatment endpoints (in a crossover design)

Change in blood pressure between placebo and treatment endpoints (in a crossover design)

Change in arterial stiffness-Pulse wave velocity between placebo and treatment endpoints (in a crossover design)

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)

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)

Change in blood sterols and sterol precursors (non-cholesterol sterols) levels between placebo and treatment endpoints (in a crossover design)

Change in fractional cholesterol synthesis between placebo and treatment endpoints (in a crossover design)

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.

Full Information

NCT ID

NCT02765516

First Posted

April 22, 2016

Last Updated

May 28, 2020

Sponsor

University of Manitoba

Collaborators

Mitacs, Unilever R&D, Nutritional Fundamentals for Health

1. Study Identification

Unique Protocol Identification Number

NCT02765516

Brief Title

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

Acronym

GenePredict-PS

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Terminated

Why Stopped

Inability to recruit

Study Start Date

July 5, 2017 (Actual)

Primary Completion Date

December 31, 2019 (Actual)

Study Completion Date

December 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Manitoba

Collaborators

Mitacs, Unilever R&D, Nutritional Fundamentals for Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia, Cardiovascular Disease

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

43 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Plant sterols

Arm Type

Active Comparator

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Other

Intervention Name(s)

Plant sterols

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame