Cardiovascular DiseasesPhase 2/3NCT00083824
Estrogen, HDL, and Coronary Heart Disease in Women
A Phase 2/3 study testing Estrogens, Conjugated (USP) and Medroxyprogesterone 17-Acetate in people with Cardiovascular Diseases and Coronary Disease, run by Tufts University at 1 site in United States.
Trial summary
To clarify the effects of estrogen, with or without progestin, on high density lipoprotein (HDL) in postmenopausal women. Read more about this study
- Who is it for?
- Ages 55 to 80 years, women only
- Conditions the study is for
- Cardiovascular Diseases, Coronary Disease, Heart Diseases
- What is being tested?
- Estrogens, Conjugated (USP) and Medroxyprogesterone 17-Acetate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 309 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2004to Feb 2007
- Phase
- Phase 2/3
- 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 55 to 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age >55 years without natural menses for at least 5 years or a serum FSH levels >40 IU/L without natural menses for at least 1 y or bilateral oophorectomy documented coronary artery disease
Who cannot join
- history of breast or endometrial carcinoma history of deep-vein thrombosis or pulmonary embolism previous or planned coronary bypass gallstones fasting TG levels >400 mg/dl uncontrolled diabetes uncontrolled hypertension serum creatinine >2 mg/dl a >70% stenosis of the left main coronary artery.
Trial locations and contacts
1 site in 1 country.
United States1 site
HNRCA at Tufts University
Boston, Massachusetts, 02111
About this study
To clarify the effects of estrogen, with or without progestin, on high density lipoprotein (HDL) in postmenopausal women.
Read the detailed description
BACKGROUND:
Coronary heart disease (CHD) is the leading cause of death and disability in postmenopausal women in the United States. Low plasma levels of high-density lipoprotein cholesterol (HDL-C) are a well-established risk factor for CHD. Elevated plasma triglyceride (TG) levels are also a risk factor for CHD in women. HDL particles are heterogeneous in composition (containing apo A-I only, LpAI, or apo A-I and apo A-II, LpAIAII) and charge and size (preBeta1, preBeta2, alpha1-3, preAlpha1-4). Different HDL subpopulations have different physiological functions and therefore may vary in their anti-atherogenic potential. Changes in alpha1 HDL subpopulations are a predictor of coronary disease progression in men. Hormonal replacement therapy (HRT) increases plasma levels of HDL-C, but has adverse effects on TG and C-reactive protein (CRP) levels. While observational studies had indicated a protective role of HRT in CHD, recent intervention studies have shown no CHD protection with the use of HRT. Our preliminary data indicate that there is a large inter-individual variability in HDL subpopulations and TG-rich lipoprotein remnants response to HRT.
The study uses the Estrogen Replacement and Atherosclerosis (ERA) trial which offers a unique opportunity to clarify the effects of estrogen with or without progestin on HDL and its subpopulation and TG-rich particles, and the effect of genetic polymorphisms on the response of these parameters to HRT. In addition, the ERA study will allow testing of the hypothesis that HRT may be of benefit to those postmenopausal women who experience large increases in HDL subpopulations (regardless of their overall effect on HDL cholesterol), without significant changes in TG levels. In addition, by looking at the TG and remnants of TG-rich lipoproteins, this study will enable a dissection of the beneficial and the adverse effects of HRT. The ERA population consists of 309 postmenopausal women who have established CHD and have participated in a randomized, placebo controlled, double-blind study of the effects of placebo (n-105), estrogen (n=100), and estrogen plus progestin (n=104) on the progression of coronary atherosclerosis, as assessed by quantitative coronary angiography. The trial showed no difference in coronary atherosclerosis progression across treatment groups after a mean follow-up of 3.2 years.
DESIGN NARRATIVE:
The study will clarify the effects of estrogen, with or without progestin, on HDL and its subpopulations and on lipoprotein remnants. It will also examine the impact of changes in HDL subpopulations and in lipoprotein remnants during HRT on progression of coronary atherosclerosis. These studies will be conducted in participants in the Estrogen Replacement and Atherosclerosis (ERA) trial, a randomized, placebo-controlled study of HRT and progression of atherosclerosis in postmenopausal women with CHD (n=309), in whom baseline and follow-up angiographic measurements of coronary artery diameter have been obtained. The following HDL parameters will be measured: preBeta1, preBeta2, alpha1-3, preAlpha1-4 HDL subpopulations by 2dGE, LpAI and LpAIAII in plasma and apo C-III in HDL and total plasma by immuno-electrophoresis, lipoprotein remnants by an immunoseparation method, and polymorphisms at gene loci involved in HDL metabolism (lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein, scavenger receptor B1, and ATPA1 receptor). Hypotheses tested are: 1) these HDL parameters and lipoprotein remnants will be significantly associated with severity of CHD at baseline; and 2) HRT-related changes in these parameters will predict coronary atherosclerosis progression in the ERA participants.
- Being tested
- Estrogens, Conjugated (USP), Medroxyprogesterone 17-Acetate, Placebo
- Medical subject headings
- Cardiovascular Diseases, Coronary Disease, Heart Diseases, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estrogens, Conjugated (USP)Drug
Also called Premarin
0.625 mg/day QID for 3 years
Medroxyprogesterone 17-AcetateDrug
Also called Provera
2.5 mg/day QID for 3 years
PlaceboDrug
Also called Sugar Pill
2 pills/day QID for 3 years
| Study group | Role | What they receive |
|---|---|---|
| Sugar Pill | Placebo comparator | Placebo Receives: Drug: Placebo |
| Estrogens, Conjugated (USP) | Experimental | Conjugated Equine Estrogen 0.625 mg/day for 3 years, drug Receives: Drug: Estrogens, Conjugated (USP) |
| Medroxyprogesterone 17-acetate | Experimental | Conjugated Equine Estrogen 0.625 mg/day plus Medroxyprogesterone Acetate 2.5 mg/day Receives: Drug: Estrogens, Conjugated (USP); Drug: Medroxyprogesterone 17-Acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
HDL subpopulation distribution and composition
To assess the effect of hormonal replacement therapy on HDL subpopulation profile and HDL composition in postmenopausal women with established CHD
Measured: 1 year
Secondary outcomes (1)
Remnant lipoprotein cholesterol
To assess the effect of hormonal replacement therapy on remnant lipoprotein cholesterol levels in postmenopausal women with established CHD
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2004 (estimated)
- Study startMar 2004
- Primary completionFeb 2007
- Study completionFeb 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 309 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Stefania lamon-Fava, Tufts University
- Investigators
- Stefania Lamon-Fava, Principal investigator, Tufts UniversityDavid M Herrington, MD, Study director, Wake Forest University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00083824
- Sponsor's protocol ID
- 1253
- Other IDs
- R01HL070081
- Status last verified
- Apr 2016
- First submitted
- 2 Jun 2004
- Last updated
- 21 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Herrington DM, Reboussin DM, Brosnihan KB, Sharp PC, Shumaker SA, Snyder TE, Furberg CD, Kowalchuk GJ, Stuckey TD, Rogers WJ, Givens DH, Waters D. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med. 2000 Aug 24;343(8):522-9. doi: 10.1056/NEJM200008243430801.
PubMed 10954759Lamon-Fava S, Herrington DM, Reboussin DM, Sherman M, Horvath K, Schaefer EJ, Asztalos BF. Changes in remnant and high-density lipoproteins associated with hormone therapy and progression of coronary artery disease in postmenopausal women. Atherosclerosis. 2009 Jul;205(1):325-30. doi: 10.1016/j.atherosclerosis.2008.12.020. Epub 2008 Dec 24.
PubMed 19155011Lamon-Fava S, Herrington DM, Reboussin DM, Sherman M, Horvath KV, Cupples LA, White C, Demissie S, Schaefer EJ, Asztalos BF. Plasma levels of HDL subpopulations and remnant lipoproteins predict the extent of angiographically-defined coronary artery disease in postmenopausal women. Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):575-9. doi: 10.1161/ATVBAHA.107.157123. Epub 2008 Jan 3.
PubMed 18174456Lamon-Fava S, Asztalos BF, Howard TD, Reboussin DM, Horvath KV, Schaefer EJ, Herrington DM. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women. Clin Endocrinol (Oxf). 2010 Feb;72(2):169-75. doi: 10.1111/j.1365-2265.2009.03644.x. Epub 2009 May 29.
PubMed 19489872Lamon-Fava S, Herrington DM, Horvath KV, Schaefer EJ, Asztalos BF. Effect of hormone replacement therapy on plasma lipoprotein levels and coronary atherosclerosis progression in postmenopausal women according to type 2 diabetes mellitus status. Metabolism. 2010 Dec;59(12):1794-800. doi: 10.1016/j.metabol.2010.05.012. Epub 2010 Jun 26.
PubMed 20580029
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Estrogen, HDL, and Coronary Heart Disease in Women
- ClinicalTrials.gov ID
- NCT00083824
- Acronym / sponsor ID
- 1253
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 309 participants (actual)
- Lead sponsor
- Tufts UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Mar 2004
- Primary completion
- Feb 2007 (actual)
- Study completion
- Feb 2007 (actual)
- First posted
- 4 Jun 2004 (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.
To clarify the effects of estrogen, with or without progestin, on high density lipoprotein (HDL) in postmenopausal women.
Detailed description
BACKGROUND:
Coronary heart disease (CHD) is the leading cause of death and disability in postmenopausal women in the United States. Low plasma levels of high-density lipoprotein cholesterol (HDL-C) are a well-established risk factor for CHD. Elevated plasma triglyceride (TG) levels are also a risk factor for CHD in women. HDL particles are heterogeneous in composition (containing apo A-I only, LpAI, or apo A-I and apo A-II, LpAIAII) and charge and size (preBeta1, preBeta2, alpha1-3, preAlpha1-4). Different HDL subpopulations have different physiological functions and therefore may vary in their anti-atherogenic potential. Changes in alpha1 HDL subpopulations are a predictor of coronary disease progression in men. Hormonal replacement therapy (HRT) increases plasma levels of HDL-C, but has adverse effects on TG and C-reactive protein (CRP) levels. While observational studies had indicated a protective role of HRT in CHD, recent intervention studies have shown no CHD protection with the use of HRT. Our preliminary data indicate that there is a large inter-individual variability in HDL subpopulations and TG-rich lipoprotein remnants response to HRT.
The study uses the Estrogen Replacement and Atherosclerosis (ERA) trial which offers a unique opportunity to clarify the effects of estrogen with or without progestin on HDL and its subpopulation and TG-rich particles, and the effect of genetic polymorphisms on the response of these parameters to HRT. In addition, the ERA study will allow testing of the hypothesis that HRT may be of benefit to those postmenopausal women who experience large increases in HDL subpopulations (regardless of their overall effect on HDL cholesterol), without significant changes in TG levels. In addition, by looking at the TG and remnants of TG-rich lipoproteins, this study will enable a dissection of the beneficial and the adverse effects of HRT. The ERA population consists of 309 postmenopausal women who have established CHD and have participated in a randomized, placebo controlled, double-blind study of the effects of placebo (n-105), estrogen (n=100), and estrogen plus progestin (n=104) on the progression of coronary atherosclerosis, as assessed by quantitative coronary angiography. The trial showed no difference in coronary atherosclerosis progression across treatment groups after a mean follow-up of 3.2 years.
DESIGN NARRATIVE:
The study will clarify the effects of estrogen, with or without progestin, on HDL and its subpopulations and on lipoprotein remnants. It will also examine the impact of changes in HDL subpopulations and in lipoprotein remnants during HRT on progression of coronary atherosclerosis. These studies will be conducted in participants in the Estrogen Replacement and Atherosclerosis (ERA) trial, a randomized, placebo-controlled study of HRT and progression of atherosclerosis in postmenopausal women with CHD (n=309), in whom baseline and follow-up angiographic measurements of coronary artery diameter have been obtained. The following HDL parameters will be measured: preBeta1, preBeta2, alpha1-3, preAlpha1-4 HDL subpopulations by 2dGE, LpAI and LpAIAII in plasma and apo C-III in HDL and total plasma by immuno-electrophoresis, lipoprotein remnants by an immunoseparation method, and polymorphisms at gene loci involved in HDL metabolism (lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein, scavenger receptor B1, and ATPA1 receptor). Hypotheses tested are: 1) these HDL parameters and lipoprotein remnants will be significantly associated with severity of CHD at baseline; and 2) HRT-related changes in these parameters will predict coronary atherosclerosis progression in the ERA participants.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sugar Pill | Placebo comparator | Drug: PlaceboPlacebo |
| Estrogens, Conjugated (USP) | Experimental | Drug: Estrogens, Conjugated (USP)Conjugated Equine Estrogen 0.625 mg/day for 3 years, drug |
| Medroxyprogesterone 17-acetate | Experimental | Drug: Estrogens, Conjugated (USP), Drug: Medroxyprogesterone 17-AcetateConjugated Equine Estrogen 0.625 mg/day plus Medroxyprogesterone Acetate 2.5 mg/day |
Who may qualify
- Ages
- 55 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- age >55 years without natural menses for at least 5 years or a serum FSH levels >40 IU/L without natural menses for at least 1 y or bilateral oophorectomy documented coronary artery disease
Key exclusion criteria (1 listed)
- history of breast or endometrial carcinoma history of deep-vein thrombosis or pulmonary embolism previous or planned coronary bypass gallstones fasting TG levels >400 mg/dl uncontrolled diabetes uncontrolled hypertension serum creatinine >2 mg/dl a >70% stenosis of the left main coronary artery.
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 |
|---|---|---|
| Estrogens, Conjugated (USP)Also: Premarin0.625 mg/day QID for 3 years | Drug | Estrogens, Conjugated (USP), Medroxyprogesterone 17-acetate |
| Medroxyprogesterone 17-AcetateAlso: Provera2.5 mg/day QID for 3 years | Drug | Medroxyprogesterone 17-acetate |
| PlaceboAlso: Sugar Pill2 pills/day QID for 3 years | Drug | Sugar Pill |
Primary outcome
HDL subpopulation distribution and composition
Time frame: 1 year
To assess the effect of hormonal replacement therapy on HDL subpopulation profile and HDL composition in postmenopausal women with established CHD
1 secondary outcome
Remnant lipoprotein cholesterol
Time frame: 1 year
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 21 Apr 2016.
- Background: PubMed 10954759Herrington DM, Reboussin DM, Brosnihan KB, Sharp PC, Shumaker SA, Snyder TE, Furberg CD, Kowalchuk GJ, Stuckey TD, Rogers WJ, Givens DH, Waters D. Effects of estrogen replacement on the progression of coronary-artery atherosclerosis. N Engl J Med. 2000 Aug 24;343(8):522-9. doi: 10.1056/NEJM200008243430801.
- Results publication: PubMed 19155011Lamon-Fava S, Herrington DM, Reboussin DM, Sherman M, Horvath K, Schaefer EJ, Asztalos BF. Changes in remnant and high-density lipoproteins associated with hormone therapy and progression of coronary artery disease in postmenopausal women. Atherosclerosis. 2009 Jul;205(1):325-30. doi: 10.1016/j.atherosclerosis.2008.12.020. Epub 2008 Dec 24.
- Results publication: PubMed 18174456Lamon-Fava S, Herrington DM, Reboussin DM, Sherman M, Horvath KV, Cupples LA, White C, Demissie S, Schaefer EJ, Asztalos BF. Plasma levels of HDL subpopulations and remnant lipoproteins predict the extent of angiographically-defined coronary artery disease in postmenopausal women. Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):575-9. doi: 10.1161/ATVBAHA.107.157123. Epub 2008 Jan 3.
- Results publication: PubMed 19489872Lamon-Fava S, Asztalos BF, Howard TD, Reboussin DM, Horvath KV, Schaefer EJ, Herrington DM. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women. Clin Endocrinol (Oxf). 2010 Feb;72(2):169-75. doi: 10.1111/j.1365-2265.2009.03644.x. Epub 2009 May 29.
- Results publication: PubMed 20580029Lamon-Fava S, Herrington DM, Horvath KV, Schaefer EJ, Asztalos BF. Effect of hormone replacement therapy on plasma lipoprotein levels and coronary atherosclerosis progression in postmenopausal women according to type 2 diabetes mellitus status. Metabolism. 2010 Dec;59(12):1794-800. doi: 10.1016/j.metabol.2010.05.012. Epub 2010 Jun 26.
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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.
Stefania Lamon-Fava principal investigator
Tufts University
David M Herrington, MD study director
Wake Forest University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Estrogens, Conjugated (USP) and Medroxyprogesterone 17-Acetate in people with Cardiovascular Diseases and Coronary Disease, run by Tufts University at 1 site in United States.
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 1 inclusion and 1 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 21 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 United States. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
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?
HDL subpopulation distribution and composition (time frame: 1 year). 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 NCT00083824, which also lists 5 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 21 Apr 2016.