HypercholesterolemiaGenePredict-PSNCT02765516
Genetic Basis for Prediction of Non-responders to Dietary Plant Sterol Intervention
A study testing Plant sterols in people with Hypercholesterolemia and Cardiovascular Disease, run by University of Manitoba at 1 site in Canada.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypercholesterolemia, Cardiovascular Disease
- What is being tested?
- Plant sterols
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 1 siteCanada
- Study dates
- 5 Jul 2017to 31 Dec 2019
- Phase
- Interventional
- 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Department of Human Nutritional sciences, University of Manitoba
Winnipeg, Manitoba, R3T2N2
About this study
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.
Read the 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.
- Conditions
- Hypercholesterolemia, Cardiovascular Disease
- Being tested
- Plant sterols, Placebo
- Medical subject headings
- Hypercholesterolemia, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plant sterolsOther
2.0g/day of plant sterols incorporated into margarine to be consumed for 28 days
PlaceboOther
Identical margarine without additional plant sterols to be consumed for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Plant sterols | Active comparator | Not described Receives: Other: Plant sterols |
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in fasting low-density lipoprotein cholesterol (LDL-C) levels between placebo and treatment endpoints (in a crossover design)
Measured: 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)
Measured: Endpoint (Days 28,29) of each treatment period
Change in fasting high-density lipoprotein cholesterol levels between placebo and treatment endpoints
Measured: Endpoint (Days 28,29) of each treatment period
Change in fasting triglyceride (TG) levels between placebo and treatment endpoints (in a crossover design)
Measured: Endpoint (Days 28,29) of each treatment period
Change in body weight between placebo and treatment endpoints (in a crossover design)
Measured: Endpoint (Days 28,29) of each treatment period
Change in body mass index (BMI) between placebo and treatment endpoints (in a crossover design)
Measured: Endpoint (Days 28,29) of each treatment period
Change in waist circumference between placebo and treatment endpoints (in a crossover design)
Measured: Endpoint (Days 28,29) of each treatment period
Change in blood pressure between placebo and treatment endpoints (in a crossover design)
Measured: Endpoint (Days 28,29) of each treatment period
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).
Measured: Endpoint (Days 28,29) of each treatment period
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).
Measured: Endpoint (Days 28,29) of each treatment period
Change in fasting glucose levels between placebo and treatment endpoints (in a crossover design)
Measured: 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)
Measured: Endpoint (Days 28,29) of each treatment period
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.
Measured: Endpoint (Day 28,29) of each treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2016 (estimated)
- Study start5 Jul 2017
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Why it stopped: Inability to recruit
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 HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by University of ManitobaThe 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manitoba
- Sponsor type
- University, hospital or other
- Collaborators
- Mitacs, Unilever R&D, Nutritional Fundamentals for Health
- Responsible party
- Principal investigator, Dr. J. House, University of Manitoba
- Investigators
- James House, PhD, Principal investigator, University of ManitobaDylan Mackay, PhD, Principal investigator, University of Manitoba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02765516
- Sponsor's protocol ID
- MITACS Converge MC00009
- Acronym
- GenePredict-PS
- Status last verified
- May 2020
- First submitted
- 22 Apr 2016
- Last updated
- 1 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 32487131
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Basis for Prediction of Non-responders to Dietary Plant Sterol Intervention
- ClinicalTrials.gov ID
- NCT02765516
- Acronym / sponsor ID
- GenePredict-PS / MITACS Converge MC00009
- Conditions
- Hypercholesterolemia, Cardiovascular Disease
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inability to recruit
- Enrolment
- 43 participants (actual)
- Lead sponsor
- University of ManitobaUniversity, hospital or other
- Collaborators
- Mitacs, Unilever R&D, Nutritional Fundamentals for Health
- Study start
- 5 Jul 2017 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 6 May 2016 (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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Plant sterols | Active comparator | Other: Plant sterols |
| Placebo | Placebo comparator | Other: Placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (12 listed)
- 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
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 |
|---|---|---|
| Plant sterols2.0g/day of plant sterols incorporated into margarine to be consumed for 28 days | Other | Plant sterols |
| PlaceboIdentical margarine without additional plant sterols to be consumed for 28 days | Other | Placebo |
Primary outcome
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
12 secondary outcomes
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
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
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
Results and safety
The study was stopped early (reason given: Inability to recruit). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2020.
- Derived from this study: PubMed 32487131Shamloo 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.
- Individual participant dataSharing planned: Undecided
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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.
James House, PhD principal investigator
University of Manitoba
Dylan Mackay, PhD principal investigator
University of Manitoba
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Plant sterols in people with Hypercholesterolemia and Cardiovascular Disease, run by University of Manitoba 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 4 inclusion and 12 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: stopped early, as of the sponsor's last update on 1 Jun 2020. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Inability to recruit). Results are not available in the source record.
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?
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). 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 NCT02765516, 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 1 Jun 2020.