PostmenopausePhase 2NCT00149604
AFTER: Altering Fat Through Estrogen and Raloxifene
A Phase 2 study testing conjugated estrogens, Raloxifene and exercise plus mild caloric restriction for weight loss in people with Postmenopause, run by National Institute on Aging (NIA) at 1 site in United States.
Trial summary
The purpose of this study is to determine whether estrogens specifically promote a reduction in fat from abdominal regions during weight loss and/or prevent the accumulation of abdominal fat during weight gain. Read more about this study
- Who is it for?
- Ages 50 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postmenopause
- What is being tested?
- conjugated estrogens, Raloxifene and exercise plus mild caloric restriction for weight loss
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 108 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2000to Feb 2006
- Phase
- Phase 2
- 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 50 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- postmenopausal women
- aged 50-70 yr
- healthy, as determined by medical history, physical examination, blood chemistries, and a graded exercise stress test with monitoring of blood pressure and ECG
- good cognitive function.
Who cannot join
- contraindications to estrogen or raloxifene treatment, including history of or active breast cancer or other estrogen-dependent neoplasms, acute liver disease, undiagnosed vaginal bleeding, and active or history of blood clotting disorders
- mild or more severe cognitive impairment, indicated by a MMSE score <26
- clinically significant abnormal resting electrocardiogram (ECG), angina and/or ECG evidence of acute myocardial ischemia during a maximal exercise stress test
- resting blood pressure above 150 mmHg systolic or 90 mmHg diastolic
- left bundle branch blocks, A-V block greater than first degree, clinically significant arrhythmias
- congestive heart failure
Show all 10Show fewer
- pulmonary emboli in the previous 6 months
- aortic stenosis
- chronic infections
- orthopedic or other problems that would interfere with participation in the exercise program
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado at Denver and Health Sciences Center
Denver, Colorado, 80262
About this study
Official title: Modulation of Visceral Fat by Estrogens After Menopause
The purpose of this study is to determine whether estrogens specifically promote a reduction in fat from abdominal regions during weight loss and/or prevent the accumulation of abdominal fat during weight gain.
Read the detailed description
The general aim of this study is to determine whether estrogen-based hormone therapy (HT) in postmenopausal women reduces the accumulation of abdominal visceral fat and whether this is a contributing factor to the effects of estrogens on cardiovascular risk factors. An additional aim is to determine whether raloxifene, a selective estrogen receptor modulator (SERM) that is suggested to be a safer alternative to estrogen for the prevention of osteoporosis, exerts similar effects as estrogen on fat distribution. Mechanisms for possible regional differences in the regulation of fat metabolism in estrogen-sufficient vs estrogen-deficient states will be investigated, as will the extent to which estrogen status and changes in visceral adiposity are associated with changes in risk for coronary artery disease (CAD) and Type 2 diabetes mellitus (DM).
The hypotheses being tested include 1) reductions in total fat mass and total abdominal and visceral fat will be significantly greater in women treated with HT or raloxifene than in those receiving placebo treatment, 2) the accumulation of total fat mass and total abdominal and visceral fat during the 12-month follow-up period will be significantly less in women on HT or raloxifene than in those receiving placebo treatment, 3) a reduction in visceral fat mass will be associated with increased sensitivity to insulin in the breakdown of fat in the whole body, and there will be an independent enhancing effect of HT and raloxifene on insulin action, and 4) changes in risk factors for CAD and Type 2 DM will be more closely associated with changes in visceral adiposity than with changes in total fat mass or other measures of regional adiposity, independent of and in addition to the effects of HT and raloxifene on risk factors.
To meet these aims, a reduction in visceral fat will be induced in 108 postmenopausal women through a 6-month program of supervised exercise training plus mild caloric restriction. Participants will be randomized to receive HT, raloxifene, or placebo. The drug treatment will continue, but the fat reduction program will cease, during a 12-month follow-up period. Risk factors for CAD and Type 2 DM and insulin sensitivity in terms of the breakdown of fat on total body and regional adipose tissue will be evaluated before and after treatment and after the follow-up period (risk factors only). For the purpose of this application, HT refers to a regimen involving daily conjugated estrogens and, in women with a uterus, tri-monthly progestin treatment.
- Conditions
- Postmenopause
- Being tested
- conjugated estrogens, Raloxifene, exercise plus mild caloric restriction for weight loss
- Keywords
- metabolic syndrome, hormone therapy, abdominal adiposity, lipolysis
- Medical subject headings
- Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
conjugated estrogensDrug
RaloxifeneDrug
exercise plus mild caloric restriction for weight lossBehavioural
What is being measured
The primary outcome is the main question the study is designed to answer.
total body fat mass
total abdominal fat area
visceral abdominal fat area
Secondary outcomes (9)
fat-free mass
total abdominal area
resting metabolic rate
dietary energy intake
cardiovascular fitness
glucose tolerance
blood lipids and lipoproteins
sex hormones (estradiol, estrone, testosterone, sex hormone binding globulin)
glucoregulatory and anti-lipolytic insulin action
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2005 (estimated)
- Study startMar 2000
- Primary completionFeb 2006
- Study completionFeb 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for PostmenopauseStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 108 participants
Sponsor and investigators
- Lead sponsor
- National Institute on Aging (NIA)
- Sponsor type
- US National Institutes of Health
- Investigators
- Wendy M. Kohrt, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00149604
- Sponsor's protocol ID
- AG0036
- Other IDs
- R01AG018198
- Status last verified
- Dec 2009
- First submitted
- 6 Sep 2005
- Last updated
- 2 Dec 2009
- Results posted
- No
Publications
Espeland MA, Stefanick ML, Kritz-Silverstein D, Fineberg SE, Waclawiw MA, James MK, Greendale GA. Effect of postmenopausal hormone therapy on body weight and waist and hip girths. Postmenopausal Estrogen-Progestin Interventions Study Investigators. J Clin Endocrinol Metab. 1997 May;82(5):1549-56. doi: 10.1210/jcem.82.5.3925.
PubMed 9141548Margolis KL, Bonds DE, Rodabough RJ, Tinker L, Phillips LS, Allen C, Bassford T, Burke G, Torrens J, Howard BV; Women's Health Initiative Investigators. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial. Diabetologia. 2004 Jul;47(7):1175-1187. doi: 10.1007/s00125-004-1448-x. Epub 2004 Jul 14.
PubMed 15252707Jensen LB, Vestergaard P, Hermann AP, Gram J, Eiken P, Abrahamsen B, Brot C, Kolthoff N, Sorensen OH, Beck-Nielsen H, Nielsen SP, Charles P, Mosekilde L. Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women: a randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study. J Bone Miner Res. 2003 Feb;18(2):333-42. doi: 10.1359/jbmr.2003.18.2.333.
PubMed 12568411Mattiasson I, Rendell M, Tornquist C, Jeppsson S, Hulthen UL. Effects of estrogen replacement therapy on abdominal fat compartments as related to glucose and lipid metabolism in early postmenopausal women. Horm Metab Res. 2002 Oct;34(10):583-8. doi: 10.1055/s-2002-35420.
PubMed 12439787
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Visceral Fat by Estrogens After Menopause
- ClinicalTrials.gov ID
- NCT00149604
- Acronym / sponsor ID
- AG0036
- Conditions
- Postmenopause
- Keywords
- metabolic syndrome, hormone therapy, abdominal adiposity, lipolysis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants
- Lead sponsor
- National Institute on Aging (NIA)US National Institutes of Health
- Study start
- Mar 2000
- Primary completion
- Feb 2006 (actual)
- Study completion
- Feb 2006 (actual)
- First posted
- 8 Sep 2005 (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 purpose of this study is to determine whether estrogens specifically promote a reduction in fat from abdominal regions during weight loss and/or prevent the accumulation of abdominal fat during weight gain.
Detailed description
The general aim of this study is to determine whether estrogen-based hormone therapy (HT) in postmenopausal women reduces the accumulation of abdominal visceral fat and whether this is a contributing factor to the effects of estrogens on cardiovascular risk factors. An additional aim is to determine whether raloxifene, a selective estrogen receptor modulator (SERM) that is suggested to be a safer alternative to estrogen for the prevention of osteoporosis, exerts similar effects as estrogen on fat distribution. Mechanisms for possible regional differences in the regulation of fat metabolism in estrogen-sufficient vs estrogen-deficient states will be investigated, as will the extent to which estrogen status and changes in visceral adiposity are associated with changes in risk for coronary artery disease (CAD) and Type 2 diabetes mellitus (DM).
The hypotheses being tested include 1) reductions in total fat mass and total abdominal and visceral fat will be significantly greater in women treated with HT or raloxifene than in those receiving placebo treatment, 2) the accumulation of total fat mass and total abdominal and visceral fat during the 12-month follow-up period will be significantly less in women on HT or raloxifene than in those receiving placebo treatment, 3) a reduction in visceral fat mass will be associated with increased sensitivity to insulin in the breakdown of fat in the whole body, and there will be an independent enhancing effect of HT and raloxifene on insulin action, and 4) changes in risk factors for CAD and Type 2 DM will be more closely associated with changes in visceral adiposity than with changes in total fat mass or other measures of regional adiposity, independent of and in addition to the effects of HT and raloxifene on risk factors.
To meet these aims, a reduction in visceral fat will be induced in 108 postmenopausal women through a 6-month program of supervised exercise training plus mild caloric restriction. Participants will be randomized to receive HT, raloxifene, or placebo. The drug treatment will continue, but the fat reduction program will cease, during a 12-month follow-up period. Risk factors for CAD and Type 2 DM and insulin sensitivity in terms of the breakdown of fat on total body and regional adipose tissue will be evaluated before and after treatment and after the follow-up period (risk factors only). For the purpose of this application, HT refers to a regimen involving daily conjugated estrogens and, in women with a uterus, tri-monthly progestin treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 50 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- postmenopausal women
- aged 50-70 yr
- healthy, as determined by medical history, physical examination, blood chemistries, and a graded exercise stress test with monitoring of blood pressure and ECG
- good cognitive function.
Key exclusion criteria (10 listed)
- contraindications to estrogen or raloxifene treatment, including history of or active breast cancer or other estrogen-dependent neoplasms, acute liver disease, undiagnosed vaginal bleeding, and active or history of blood clotting disorders
- mild or more severe cognitive impairment, indicated by a MMSE score <26
- clinically significant abnormal resting electrocardiogram (ECG), angina and/or ECG evidence of acute myocardial ischemia during a maximal exercise stress test
- resting blood pressure above 150 mmHg systolic or 90 mmHg diastolic
- left bundle branch blocks, A-V block greater than first degree, clinically significant arrhythmias
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 |
|---|---|---|
| conjugated estrogens | Drug | – |
| Raloxifene | Drug | – |
| exercise plus mild caloric restriction for weight loss | Behavioural | – |
Primary outcome
total body fat mass
total abdominal fat area
visceral abdominal fat area
9 secondary outcomes
fat-free mass
total abdominal area
resting metabolic rate
dietary energy intake
cardiovascular fitness
glucose tolerance
blood lipids and lipoproteins
sex hormones (estradiol, estrone, testosterone, sex hormone binding globulin)
glucoregulatory and anti-lipolytic insulin action
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 2 Dec 2009.
- Background: PubMed 9141548Espeland MA, Stefanick ML, Kritz-Silverstein D, Fineberg SE, Waclawiw MA, James MK, Greendale GA. Effect of postmenopausal hormone therapy on body weight and waist and hip girths. Postmenopausal Estrogen-Progestin Interventions Study Investigators. J Clin Endocrinol Metab. 1997 May;82(5):1549-56. doi: 10.1210/jcem.82.5.3925.
- Background: PubMed 15252707Margolis KL, Bonds DE, Rodabough RJ, Tinker L, Phillips LS, Allen C, Bassford T, Burke G, Torrens J, Howard BV; Women's Health Initiative Investigators. Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial. Diabetologia. 2004 Jul;47(7):1175-1187. doi: 10.1007/s00125-004-1448-x. Epub 2004 Jul 14.
- Background: PubMed 12568411Jensen LB, Vestergaard P, Hermann AP, Gram J, Eiken P, Abrahamsen B, Brot C, Kolthoff N, Sorensen OH, Beck-Nielsen H, Nielsen SP, Charles P, Mosekilde L. Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women: a randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study. J Bone Miner Res. 2003 Feb;18(2):333-42. doi: 10.1359/jbmr.2003.18.2.333.
- Background: PubMed 12439787Mattiasson I, Rendell M, Tornquist C, Jeppsson S, Hulthen UL. Effects of estrogen replacement therapy on abdominal fat compartments as related to glucose and lipid metabolism in early postmenopausal women. Horm Metab Res. 2002 Oct;34(10):583-8. doi: 10.1055/s-2002-35420.
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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.
Wendy M. Kohrt, PhD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing conjugated estrogens, Raloxifene and exercise plus mild caloric restriction for weight loss in people with Postmenopause, run by National Institute on Aging (NIA) 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 4 inclusion and 10 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 2 Dec 2009. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
total body fat mass. 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 NCT00149604, which also lists 4 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 2 Dec 2009.