Metabolic Syndrome XPhase 3EZEmRNANCT01849068
Effects of Selective Inhibition of Cholesterol Absorption With Ezetimibe on Intestinal Cholesterol Homeostasis in Dyslipidemic Men With Insulin-resistance - a Pilot Study
A Phase 3 study testing Ezetimibe in people with Metabolic Syndrome X, run by Laval University at 1 site in Canada.
Trial summary
Ezetimibe has been shown to inhibit cholesterol absorption and several lines of evidence from in vitro systems and animal models suggest that this effect is associated with an increase in low-density lipoprotein (LDL) receptor expression in the small intestine. Read more about this study
- Who is it for?
- Ages 18 to 60 years, men only
- Conditions the study is for
- Metabolic Syndrome X
- What is being tested?
- Ezetimibe
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2013to Feb 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Men aged between 18-60 years
- Waist circumference > 102 cm
- HDL-cholesterol < 1.1 mmol/L
- Triglycerides > 1.7 mmol/L
- Fasting blood glucose > 6.1 mmol/L
- Normal blood pressure (<130/85)
Who cannot join
- Women
- Men < 18 or > 60 years
- Smokers (> 1 cigarette/day)
- Body weight variation > 10% during the last 6 months prior to the study baseline
- Subjects with a previous history of cardiovascular disease
- Subjects with type 2 diabetes
Show all 11Show fewer
- Subjects with a monogenic dyslipidemia
- Subjects on hypertension medications or medications known to affect lipoprotein metabolism or the integrity of gastrointestinal mucosa
- Subjects with endocrine or gastrointestinal disorders
- History of alcohol or drug abuse within the past 2 years
- Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
Trial locations and contacts
1 site in 1 country.
About this study
Ezetimibe has been shown to inhibit cholesterol absorption and several lines of evidence from in vitro systems and animal models suggest that this effect is associated with an increase in low-density lipoprotein (LDL) receptor expression in the small intestine. The impact of a treatment with ezetimibe on intestinal gene expression and protein mass levels of LDL receptor and other key genes involved in intestinal cholesterol homeostasis will be examined in dyslipidemic men with insulin-resistance. In the present study, gene expression studies and protein mass levels will be assessed on duodenal biopsies by real-time polymerase chain reaction (rt-PCR) and liquid chromatography-mass spectrometry (LC-MS/MS), respectively. The primary objective of this proposal is to examine the effects of ezetimibe on intestinal gene expression (rt-PCR) and protein mass levels (LC-MS/MS) of LDL receptor in dyslipidemic men with insulin-resistance. The secondary objective is to examine the impact of ezetimibe treatment on intestinal gene expression and protein mass levels of sterol regulatory element-binding protein (SREBP)-2, Niemann-Pick C1-Like1 (NPC1L1), ATP binding cassette gene (ABCG)-5/8, proprotein convertase subtilisin/kexin type 9 (PCSK9) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase.
Primary hypothesis Treatment with ezetimibe 10 mg/day will significantly increase duodenal mRNA and protein mass levels of LDL receptor in dyslipidemic men with insulin-resistance.
Secondary hypothesis Treatment with ezetimibe 10 mg/day will significantly increase duodenal mRNA and protein mass levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA reductase in dyslipidemic men with insulin-resistance.
- Conditions
- Metabolic Syndrome X
- Being tested
- Ezetimibe, Placebo
- Medical subject headings
- Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EzetimibeDrug
Also called Ezetrol
Ezetimibe 10 mg/d for 12 weeks
PlaceboDrug
Placebo for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Ezetimibe | Experimental | Not described Receives: Drug: Ezetimibe |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Intestinal mRNA Expression Levels of LDL Receptor Between the Two 12-week Interventions
We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).
We combined the results at the end of each placebo phase from both sequence (average and standard deviation).
Measured: At the end of the two 12-week interventions (Week 12 and 24)
Secondary outcomes (3)
Change in Intestinal mRNA Expression Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase Between the Two 12-week Interventions
We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).
We combined the results at the end of each placebo phase from both sequence (average and standard deviation).
Measured: At the end of the two 12-week interventions (Week 12 and 24)
Change in Intestinal Protein Levels of LDL Receptor Between the Two 12-week Interventions
We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).
We combined the results at the end of each placebo phase from both sequence (average and standard deviation).
Measured: At the end of the two 12-week interventions (Week 12 and 24)
Change in Protein Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase Between the Two 12-week Interventions
We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).
We combined the results at the end of each placebo phase from both sequence (average and standard deviation).
Measured: At the end of the two 12-week interventions (Week 12 and 24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2013 (estimated)
- Study startJun 2013
- Primary completionJun 2015
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metabolic Syndrome XStudies of the same condition, open and under way.
- More trials run by Laval UniversityThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laval University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Patrick Couture, Laval University
- Investigators
- Patrick Couture, MD, FRCP, PhD, Principal investigator, Laval University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01849068
- Sponsor's protocol ID
- INAF-B13-04-1195
- Acronym
- EZEmRNA
- Status last verified
- Mar 2016
- First submitted
- 6 May 2013
- Last updated
- 12 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Selective Inhibition of Cholesterol Absorption With Ezetimibe on Intestinal Cholesterol Homeostasis in Dyslipidemic Men With Insulin-resistance - a Pilot Study
- ClinicalTrials.gov ID
- NCT01849068
- Acronym / sponsor ID
- EZEmRNA / INAF-B13-04-1195
- Conditions
- Metabolic Syndrome X
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Laval UniversityUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Jun 2015 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 8 May 2013 (estimated)
- Results
- Posted 12 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ezetimibe has been shown to inhibit cholesterol absorption and several lines of evidence from in vitro systems and animal models suggest that this effect is associated with an increase in low-density lipoprotein (LDL) receptor expression in the small intestine. The impact of a treatment with ezetimibe on intestinal gene expression and protein mass levels of LDL receptor and other key genes involved in intestinal cholesterol homeostasis will be examined in dyslipidemic men with insulin-resistance. In the present study, gene expression studies and protein mass levels will be assessed on duodenal biopsies by real-time polymerase chain reaction (rt-PCR) and liquid chromatography-mass spectrometry (LC-MS/MS), respectively. The primary objective of this proposal is to examine the effects of ezetimibe on intestinal gene expression (rt-PCR) and protein mass levels (LC-MS/MS) of LDL receptor in dyslipidemic men with insulin-resistance. The secondary objective is to examine the impact of ezetimibe treatment on intestinal gene expression and protein mass levels of sterol regulatory element-binding protein (SREBP)-2, Niemann-Pick C1-Like1 (NPC1L1), ATP binding cassette gene (ABCG)-5/8, proprotein convertase subtilisin/kexin type 9 (PCSK9) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase.
Primary hypothesis Treatment with ezetimibe 10 mg/day will significantly increase duodenal mRNA and protein mass levels of LDL receptor in dyslipidemic men with insulin-resistance.
Secondary hypothesis Treatment with ezetimibe 10 mg/day will significantly increase duodenal mRNA and protein mass levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA reductase in dyslipidemic men with insulin-resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ezetimibe | Experimental | Drug: Ezetimibe |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Men aged between 18-60 years
- Waist circumference > 102 cm
- HDL-cholesterol < 1.1 mmol/L
- Triglycerides > 1.7 mmol/L
- Fasting blood glucose > 6.1 mmol/L
Key exclusion criteria (11 listed)
- Women
- Men < 18 or > 60 years
- Smokers (> 1 cigarette/day)
- Body weight variation > 10% during the last 6 months prior to the study baseline
- Subjects with a previous history of cardiovascular disease
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 |
|---|---|---|
| EzetimibeAlso: EzetrolEzetimibe 10 mg/d for 12 weeks | Drug | Ezetimibe |
| PlaceboPlacebo for 12 weeks | Drug | Placebo |
Primary outcome
Change in Intestinal mRNA Expression Levels of LDL Receptor Between the Two 12-week Interventions
Time frame: At the end of the two 12-week interventions (Week 12 and 24)
We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation). We combined the results at the end of each placebo phase from both sequence (average and standard deviation).
3 secondary outcomes
Change in Intestinal mRNA Expression Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase Between the Two 12-week Interventions
Time frame: At the end of the two 12-week interventions (Week 12 and 24)
Change in Intestinal Protein Levels of LDL Receptor Between the Two 12-week Interventions
Time frame: At the end of the two 12-week interventions (Week 12 and 24)
Change in Protein Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase Between the Two 12-week Interventions
Time frame: At the end of the two 12-week interventions (Week 12 and 24)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Patrick Couture, MD, FRCP, PhD principal investigator
Laval University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ezetimibe in people with Metabolic Syndrome X, run by Laval University 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 6 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 12 Apr 2016. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Intestinal mRNA Expression Levels of LDL Receptor Between the Two 12-week Interventions (time frame: At the end of the two 12-week interventions (Week 12 and 24)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Apr 2016.