AFTER: Altering Fat Through Estrogen and Raloxifene

Postmenopause Clinical Trial

Official title:

Modulation of Visceral Fat by Estrogens After Menopause

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00149604
• Other study ID #: AG0036
• Secondary ID: R01AG018198
• Status: Completed
• Phase: Phase 2
• First received: September 6, 2005
• Last updated: December 1, 2009
• Start date: March 2000
• Est. completion date: February 2006

Study information

• Verified date: December 2009
• Source: National Institute on Aging (NIA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: February 2006
• Est. primary completion date: February 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 50 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Postmenopause

Intervention

Drug:
• conjugated estrogens

• Raloxifene

Behavioral:
• exercise plus mild caloric restriction for weight loss

Locations

Country	Name	City	State
United States	University of Colorado at Denver and Health Sciences Center	Denver	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. — View Citation

Jensen LB, Vestergaard P, Hermann AP, Gram J, Eiken P, Abrahamsen B, Brot C, Kolthoff N, Sørensen 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. — View Citation

Margolis 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):1175-87. Epub 2004 Jul 14. — View Citation

Mattiasson I, Rendell M, Törnquist C, Jeppsson S, Hulthén 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	total body fat mass
Primary	total abdominal fat area
Primary	visceral abdominal fat area
Secondary	fat-free mass
Secondary	total abdominal area
Secondary	resting metabolic rate
Secondary	dietary energy intake
Secondary	cardiovascular fitness
Secondary	glucose tolerance
Secondary	blood lipids and lipoproteins
Secondary	sex hormones (estradiol, estrone, testosterone, sex hormone binding globulin)
Secondary	glucoregulatory and anti-lipolytic insulin action