AFTER: Altering Fat Through Estrogen and Raloxifene

This study has been completed.
Sponsor:
Information provided by:
National Institute on Aging (NIA)
ClinicalTrials.gov Identifier:
NCT00149604
First received: September 6, 2005
Last updated: December 1, 2009
Last verified: December 2009
  Purpose

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.


Condition Intervention Phase
Postmenopause
Drug: conjugated estrogens
Drug: Raloxifene
Behavioral: exercise plus mild caloric restriction for weight loss
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Modulation of Visceral Fat by Estrogens After Menopause

Resource links provided by NLM:


Further study details as provided by National Institute on Aging (NIA):

Primary Outcome Measures:
  • total body fat mass
  • total abdominal fat area
  • visceral abdominal fat area

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 108
Study Start Date: March 2000
Study Completion Date: February 2006
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   50 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • pulmonary emboli in the previous 6 months
  • aortic stenosis
  • chronic infections
  • orthopedic or other problems that would interfere with participation in the exercise program
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00149604

Locations
United States, Colorado
University of Colorado at Denver and Health Sciences Center
Denver, Colorado, United States, 80262
Sponsors and Collaborators
Investigators
Principal Investigator: Wendy M. Kohrt, PhD University of Colorado, Denver
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00149604     History of Changes
Other Study ID Numbers: AG0036, R01AG018198
Study First Received: September 6, 2005
Last Updated: December 1, 2009
Health Authority: United States: Federal Government

Keywords provided by National Institute on Aging (NIA):
metabolic syndrome
hormone therapy
abdominal adiposity
lipolysis

Additional relevant MeSH terms:
Estrogens, Conjugated (USP)
Estrogens
Raloxifene
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on August 21, 2014