HyperlipidemiaPhase 4NCT01131832
Genetic Basis for Heterogeneity in Response of Plasma Lipids to Plant Sterols
A Phase 4 study testing Plant sterol in people with Hyperlipidemia, run by University of Manitoba at 2 sites in 2 countries.
Trial summary
The substantial range of individual responsiveness to plant sterols has important ramifications. Marked differences across individuals in particular aspects of the cholesterol metabolic pathway must alter the impact of plant sterol consumption. Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Hyperlipidemia
- What is being tested?
- Plant sterol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 71 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Sep 2010to Feb 2012
- Phase
- Phase 4
- 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 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- fasting serum LDL cholesterol >3.0 mmol/L
- high or low lathosterol to cholesterol ratio
Who cannot join
- smoking
- use of lipid lowering therapy
- documented cardiovascular/atherosclerotic disease
- inflammatory disease
- diabetes
- uncontrolled hypertension
Show all 11Show fewer
- kidney disease
- liver disease
- other systemic diseases
- cancer
- chronic alcohol consumption (> 2 servings/day)
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
USDA-ARS, Beltsville Human Nutrition Research Center
Beltsville, Maryland, 20705
Canada1 site
Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba
Winnipeg, Manitoba, R3T 6C5
About this study
The substantial range of individual responsiveness to plant sterols has important ramifications. Marked differences across individuals in particular aspects of the cholesterol metabolic pathway must alter the impact of plant sterol consumption. As such, a pronounced need exists to understand the genetic and metabolic factors that explain the substantial degree of heterogeneity in response of lipid concentrations to plant sterols across individuals. The primary focus of this trial is to delineate the impact of differing cholesterol synthesis levels on response of LDL-C and other plasma lipids to plant sterol consumption. Participants pre-identified as high or low endogenous cholesterol synthesizers, according to their screening level of lathosterol to cholesterol ratios, will be given PS or a placebo containing margarine to consume under supervision for 4 weeks in a crossover design. The trial will characterize the responsiveness of the participants' total, LDL, and HDL cholesterol, as well as triacylglycerol (TG) concentrations, to plant sterol consumption. This research will determine if cholesterol synthesis phenotype predicts the responsiveness of lipids to plant sterol consumption. Variations in candidate genes involved in cholesterol metabolism will also be investigated in order to find associations with both cholesterol metabolism phenotypes and responsiveness of lipids to plant sterols. The output of this research will be to advance the knowledge of which genetic factors influence the degree of cardiovascular benefit derived from plant sterols through lipid lowering.
- Conditions
- Hyperlipidemia
- Being tested
- Plant sterol, Placebo
- Keywords
- Cholesterol, Plant sterols, Non-response, SNPs,
- Medical subject headings
- Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plant sterolDietary supplement
PlaceboDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Plant sterol | Experimental | Plant sterol supplementation, 2 grams per day of plant sterols in a margarine Receives: Dietary Supplement: Plant sterol; Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum Lipids
Total Cholesterol, LDL-C, HDL-C, Triglycerides
Measured: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
Serum non-cholesterol sterols
Lathosterol,Lanosterol,Desmosterol,Sitosterol,Campesterol,Cholestanol,
Measured: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
Genotype via single nucleotide polymorphism analysis
SNP genotyping in genes related to cholesterol metabolism
Measured: Baseline
Secondary outcomes (2)
Cholesterol synthesis measurement by deuterium incorporation
Cholesterol biosynthesis will be determined as the rate of incorporation of deuterium from body water into red blood cell membrane free cholesterol over a 24 hour period (day 27 to day 28 of each period). The change in deuterium enrichment within red blood cell free cholesterol will be determined as an index of synthesis, the fractional synthesis rate (FSR) of cholesterol.
Measured: Endpoint (Day 27,28) of each experimental period
Change in cholesterol absorption due to plant sterol consumption
Ninety-six hours before the end of each period, participants will ingest 65 mg [3, 4-13C]-cholesterol. The 13C-cholesterol will be dissolved in 5 g of warmed margarine, and consumed on a slice of bread. A fasted blood sample will be taken at baseline on day 24 prior to isotope administration, as well as fasting samples on days 25, 26, 27 and 28 to monitor enrichment levels of 13C-cholesterol in plasma total cholesterol. The area under the curve of 13C-cholesterol from 0-96 hours (days 24-28) at the end of the control period will be compared to the same area under the curve at the end of the plant sterol period to determine the change in cholesterol absorption due to plant sterol consumption.
Measured: Change in cholesterol absorption from control period (measured over days 24-28) to plant sterol period (days 24-28)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2010 (estimated)
- Study startSep 2010
- Primary completionFeb 2012
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HyperlipidemiaStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manitoba
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Peter J. H. Jones, University of Manitoba
- Investigators
- Peter J.H. Jones, PhD, Principal investigator, Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01131832
- Sponsor's protocol ID
- B2007:073
- Status last verified
- May 2017
- First submitted
- 25 May 2010
- Last updated
- 9 May 2017
- Results posted
- No
Publications
MacKay DS, Eck PK, Gebauer SK, Baer DJ, Jones PJ. CYP7A1-rs3808607 and APOE isoform associate with LDL cholesterol lowering after plant sterol consumption in a randomized clinical trial. Am J Clin Nutr. 2015 Oct;102(4):951-7. doi: 10.3945/ajcn.115.109231. Epub 2015 Sep 2.
PubMed 26333513Mackay DS, Gebauer SK, Eck PK, Baer DJ, Jones PJ. Lathosterol-to-cholesterol ratio in serum predicts cholesterol-lowering response to plant sterol consumption in a dual-center, randomized, single-blind placebo-controlled trial. Am J Clin Nutr. 2015 Mar;101(3):432-9. doi: 10.3945/ajcn.114.095356. Epub 2015 Jan 14.
PubMed 25733626
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Basis for Heterogeneity in Response of Plasma Lipids to Plant Sterols
- ClinicalTrials.gov ID
- NCT01131832
- Acronym / sponsor ID
- B2007:073
- Conditions
- Hyperlipidemia
- Keywords
- Cholesterol, Plant sterols, Non-response, SNPs,
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- University of ManitobaUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 27 May 2010 (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 substantial range of individual responsiveness to plant sterols has important ramifications. Marked differences across individuals in particular aspects of the cholesterol metabolic pathway must alter the impact of plant sterol consumption. As such, a pronounced need exists to understand the genetic and metabolic factors that explain the substantial degree of heterogeneity in response of lipid concentrations to plant sterols across individuals. The primary focus of this trial is to delineate the impact of differing cholesterol synthesis levels on response of LDL-C and other plasma lipids to plant sterol consumption. Participants pre-identified as high or low endogenous cholesterol synthesizers, according to their screening level of lathosterol to cholesterol ratios, will be given PS or a placebo containing margarine to consume under supervision for 4 weeks in a crossover design. The trial will characterize the responsiveness of the participants' total, LDL, and HDL cholesterol, as well as triacylglycerol (TG) concentrations, to plant sterol consumption. This research will determine if cholesterol synthesis phenotype predicts the responsiveness of lipids to plant sterol consumption. Variations in candidate genes involved in cholesterol metabolism will also be investigated in order to find associations with both cholesterol metabolism phenotypes and responsiveness of lipids to plant sterols. The output of this research will be to advance the knowledge of which genetic factors influence the degree of cardiovascular benefit derived from plant sterols through lipid lowering.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Plant sterol | Experimental | Dietary Supplement: Plant sterol, Dietary Supplement: PlaceboPlant sterol supplementation, 2 grams per day of plant sterols in a margarine |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- fasting serum LDL cholesterol >3.0 mmol/L
- high or low lathosterol to cholesterol ratio
Key exclusion criteria (11 listed)
- smoking
- use of lipid lowering therapy
- documented cardiovascular/atherosclerotic disease
- inflammatory disease
- diabetes
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 sterol | Dietary supplement | Plant sterol |
| Placebo | Dietary supplement | Plant sterol |
Primary outcome
Serum Lipids
Time frame: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
Total Cholesterol, LDL-C, HDL-C, Triglycerides
Serum non-cholesterol sterols
Time frame: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period
Lathosterol,Lanosterol,Desmosterol,Sitosterol,Campesterol,Cholestanol,
Genotype via single nucleotide polymorphism analysis
Time frame: Baseline
SNP genotyping in genes related to cholesterol metabolism
2 secondary outcomes
Cholesterol synthesis measurement by deuterium incorporation
Time frame: Endpoint (Day 27,28) of each experimental period
Change in cholesterol absorption due to plant sterol consumption
Time frame: Change in cholesterol absorption from control period (measured over days 24-28) to plant sterol period (days 24-28)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2017.
- Derived from this study: PubMed 26333513MacKay DS, Eck PK, Gebauer SK, Baer DJ, Jones PJ. CYP7A1-rs3808607 and APOE isoform associate with LDL cholesterol lowering after plant sterol consumption in a randomized clinical trial. Am J Clin Nutr. 2015 Oct;102(4):951-7. doi: 10.3945/ajcn.115.109231. Epub 2015 Sep 2.
- Derived from this study: PubMed 25733626Mackay DS, Gebauer SK, Eck PK, Baer DJ, Jones PJ. Lathosterol-to-cholesterol ratio in serum predicts cholesterol-lowering response to plant sterol consumption in a dual-center, randomized, single-blind placebo-controlled trial. Am J Clin Nutr. 2015 Mar;101(3):432-9. doi: 10.3945/ajcn.114.095356. Epub 2015 Jan 14.
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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.
Peter J.H. Jones, PhD principal investigator
Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Plant sterol in people with Hyperlipidemia, run by University of Manitoba at 2 sites in 2 countries.
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 2 inclusion and 11 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: finished, as of the sponsor's last update on 9 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Serum Lipids (time frame: Baseline (Day 1,2) and Endpoint (Day 27,28) of each experimental period). The study lists 3 primary outcomes in all. 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 NCT01131832, which also lists 2 linked publications.
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 9 May 2017.