HypercholesterolemiaNCT00848276
Sex Hormones and Blood PCSK9 Levels
An observational study of Hypercholesterolemia, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial summary
This study measures a recently discovered protein named PCSK9 (Proprotein convertase subtilisin kexin 9) in blood to see if it is influenced by male and female sex hormones. PCSK9 has recently been shown to control cholesterol and triglyceride levels by diminishing the ability of liver cells to remove cholesterol from… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypercholesterolemia
- How many people
- 61 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2008to Sep 2010
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Primary care clincs
Who may be able to join
- Males:
- 18 years of age and older for hypogonadal males/males with prostate cancer
- Prior clinical decision to start on testosterone therapy
- Females:
- 30 years of age and older for post-menopausal women
- Prior clinical decision to start on estrogen therapy
Who cannot join
- Cognitive impairment, active or chronic hepatic or renal disease, diagnosed diabetes mellitus,alcohol consumption greater than 4 drinks/day
- receiving or needing progestogen therapy for women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Human Studies On Gender Differences In PCSK9 Function In Lipoprotein Metabolism
This study measures a recently discovered protein named PCSK9 (Proprotein convertase subtilisin kexin 9) in blood to see if it is influenced by male and female sex hormones. PCSK9 has recently been shown to control cholesterol and triglyceride levels by diminishing the ability of liver cells to remove cholesterol from blood leading to high blood cholesterol levels.
It was found in previous studies that there was a relationship between blood levels of PCSK9 and cholesterol in men but not in women. This gender difference is a new finding and it raises the question of whether male and female hormones might influence PCSK9's role as a blood cholesterol regulator.
The study requires a pre-treatment fasting blood sample and another sample 3 months after starting hormone therapy.
Read the detailed description
Proprotein convertase subtilisin kexin 9 (PCSK9) is a secreted glycoprotein that was first demonstrated to play a role in lipoprotein metabolism in 2003 when several gain-of-function single nucleotide polymorphisms (SNPs) in PCSK9 were shown to associate with autosomal dominant hypercholesterolemia (ADH). Soon after, loss-of-function nonsense and missense SNPs in PCSK9 were shown to associate with hypocholesterolemia. Much is still not known about PCSK9's mechanism of action, its substrate(s), its regulation, and factors affecting its function, but we do know that PCSK9 decreases LDL clearance through degradation of LDL receptors. We examined plasma PCSK9 and serum lipids in182 normolipidemic subjects (98 men, 84 women) and found with Spearman analysis a significant correlation between plasma PCSK9 and total cholesterol (TC), LDL-C, and TC/HDL-C in men but not in women, suggesting a gender difference in PCSK9 regulation and/or function.
Following on our unexpected but novel and exciting observation, we hypothesize: that serum levels of testosterone and estradiol would be significantly correlated with plasma PCSK9 levels, that testosterone and 17-B estradiol replacement therapies in men and women respectively would result in changes in the levels of plasma PCSK9, that testosterone and estradiol modify the effect of PCSK9 on serum lipids in different ways, explaining at least in part, the gender dichotomy in PCSK9 function, and that a significant percentage of the effect of hormone replacement therapy on lipids is mediated through PCSK9 function.
Cohort #1 will be 60 hypogonadal men and cohort #2 will be 60 postmenopausal (hypoestrogenic) women before and after testosterone and estrogen replacement therapy respectively. They will undergo measurements of plasma PCSK9, serum testosterone in men or estradiol in women and TC, triglycerides, HDL-C and LDL-C before and 3 months after starting on replacement therapy. These panel studies will allow us to evaluate whether (a) hormone replacement therapy has an effect on PCSK9, and (b) whether resulting changes in PCSK9 are then associated with lipid response.
- Conditions
- Hypercholesterolemia
- Keywords
- PCSK9, Lipoprotein metabolism, testosterone, estradiol
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Hypogonadal Men before and after starting testosterone replacement therapy | |
| 2 | Post-menopausal women before and after starting Estrogen Replacement Therapy |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2009 (estimated)
- Study startJul 2008
- Primary completionSep 2010
- Study completionSep 2010
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 Ottawa Hospital Research InstituteThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Heart and Stroke Foundation of Ontario
- Investigators
- Teik Chye Ooi, MBBS, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00848276
- Sponsor's protocol ID
- 2008138-01H
- Status last verified
- Dec 2010
- First submitted
- 19 Feb 2009
- Last updated
- 8 Dec 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
Ooi TC, Raymond A, Cousins M, Favreau C, Taljaard M, Gavin C, Jolly EE, Malone S, Eapen L, Chretien M, Mbikay M, Mayne J. Relationship between testosterone, estradiol and circulating PCSK9: Cross-sectional and interventional studies in humans. Clin Chim Acta. 2015 Jun 15;446:97-104. doi: 10.1016/j.cca.2015.03.036. Epub 2015 Apr 7.
PubMed 25858546
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Studies On Gender Differences In PCSK9 Function In Lipoprotein Metabolism
- ClinicalTrials.gov ID
- NCT00848276
- Acronym / sponsor ID
- 2008138-01H
- Conditions
- Hypercholesterolemia
- Keywords
- PCSK9, Lipoprotein metabolism, testosterone, estradiol
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Heart and Stroke Foundation of Ontario
- Study start
- Jul 2008
- Primary completion
- Sep 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 20 Feb 2009 (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.
This study measures a recently discovered protein named PCSK9 (Proprotein convertase subtilisin kexin 9) in blood to see if it is influenced by male and female sex hormones. PCSK9 has recently been shown to control cholesterol and triglyceride levels by diminishing the ability of liver cells to remove cholesterol from blood leading to high blood cholesterol levels.
It was found in previous studies that there was a relationship between blood levels of PCSK9 and cholesterol in men but not in women. This gender difference is a new finding and it raises the question of whether male and female hormones might influence PCSK9's role as a blood cholesterol regulator.
The study requires a pre-treatment fasting blood sample and another sample 3 months after starting hormone therapy.
Detailed description
Proprotein convertase subtilisin kexin 9 (PCSK9) is a secreted glycoprotein that was first demonstrated to play a role in lipoprotein metabolism in 2003 when several gain-of-function single nucleotide polymorphisms (SNPs) in PCSK9 were shown to associate with autosomal dominant hypercholesterolemia (ADH). Soon after, loss-of-function nonsense and missense SNPs in PCSK9 were shown to associate with hypocholesterolemia. Much is still not known about PCSK9's mechanism of action, its substrate(s), its regulation, and factors affecting its function, but we do know that PCSK9 decreases LDL clearance through degradation of LDL receptors. We examined plasma PCSK9 and serum lipids in182 normolipidemic subjects (98 men, 84 women) and found with Spearman analysis a significant correlation between plasma PCSK9 and total cholesterol (TC), LDL-C, and TC/HDL-C in men but not in women, suggesting a gender difference in PCSK9 regulation and/or function.
Following on our unexpected but novel and exciting observation, we hypothesize: that serum levels of testosterone and estradiol would be significantly correlated with plasma PCSK9 levels, that testosterone and 17-B estradiol replacement therapies in men and women respectively would result in changes in the levels of plasma PCSK9, that testosterone and estradiol modify the effect of PCSK9 on serum lipids in different ways, explaining at least in part, the gender dichotomy in PCSK9 function, and that a significant percentage of the effect of hormone replacement therapy on lipids is mediated through PCSK9 function.
Cohort #1 will be 60 hypogonadal men and cohort #2 will be 60 postmenopausal (hypoestrogenic) women before and after testosterone and estrogen replacement therapy respectively. They will undergo measurements of plasma PCSK9, serum testosterone in men or estradiol in women and TC, triglycerides, HDL-C and LDL-C before and 3 months after starting on replacement therapy. These panel studies will allow us to evaluate whether (a) hormone replacement therapy has an effect on PCSK9, and (b) whether resulting changes in PCSK9 are then associated with lipid response.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Hypogonadal Men before and after starting testosterone replacement therapy |
| 2 | – | –Post-menopausal women before and after starting Estrogen Replacement Therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Primary care clincs
Key inclusion criteria (6 listed)
- 18 years of age and older for hypogonadal males/males with prostate cancer
- Prior clinical decision to start on testosterone therapy
- 30 years of age and older for post-menopausal women
- Prior clinical decision to start on estrogen therapy
Key exclusion criteria (2 listed)
- Cognitive impairment, active or chronic hepatic or renal disease, diagnosed diabetes mellitus,alcohol consumption greater than 4 drinks/day
- receiving or needing progestogen therapy for women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 8 Dec 2010.
- Derived from this study: PubMed 25858546Ooi TC, Raymond A, Cousins M, Favreau C, Taljaard M, Gavin C, Jolly EE, Malone S, Eapen L, Chretien M, Mbikay M, Mayne J. Relationship between testosterone, estradiol and circulating PCSK9: Cross-sectional and interventional studies in humans. Clin Chim Acta. 2015 Jun 15;446:97-104. doi: 10.1016/j.cca.2015.03.036. Epub 2015 Apr 7.
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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.
Teik Chye Ooi, MBBS principal investigator
Ottawa Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypercholesterolemia, run by Ottawa Hospital Research Institute 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 2 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 8 Dec 2010. 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. 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 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00848276, 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 8 Dec 2010.