Prevention of Obesity in Women Via Estradiol Regulation (POWER)

November 20, 2019 updated by: University of Colorado, Denver

Estrogen Deficiency and Mechanisms of Fat Accumulation

The purpose of this study is to evaluate potential mechanisms by which estradiol deficiency accelerates fat gain and abdominal fat accumulation in women.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Many factors contribute to the current epidemic of obesity. Although estrogen status is not commonly recognized as a determinant of obesity risk in women, there is strong evidence from large randomized controlled trials that estradiol (E2)-based hormone therapy (HT) reduces weight gain by about 40% in postmenopausal women. Importantly, there is also strong evidence that E2 reduces abdominal fat accumulation, a fundamental component of the Metabolic Syndrome. Some studies suggest risks of HT outweigh the benefits for some women. However, this does not negate the importance of learning the mechanisms by which E2 influences energy balance and fat patterning.

This study uses gonadotropin releasing hormone (GnRH) analog therapy to determine the effects of chronic (5-month) sex hormone suppression on resting energy expenditure (REE), altered hypothalamic-pituitary-adrenal (HPA) axis activity, and fat gain.

It is hypothesized that REE will be reduced in response to chronic sex hormone suppression, promoting fat gain. It is also hypothesized that stress-induced hypothalamic-pituitary-adrenal (HPA)axis activity will be amplified during sex hormone suppression; altered HPA axis activity leading to cortisol excess causes abdominal fat accumulation. Finally, it is hypothesized that E2 add-back therapy will lessen these responses.

Participants will be randomized so that half of the women in each treatment arm will participate in an exercise training program, consisting of progressive resistance exercise to prevent the decline in fat-free mass (FFM) and the increase in fat mass that has been observed in young women in response to GnRH analog therapy.

Study Type

Interventional

Enrollment (Actual)

79

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Denver

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 49 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Healthy premenopausal women, aged 18 to 49 years
  • Regular menses (no missed cycles in previous year; cycle length 25-35 days)
  • Positive luteinizing hormone test or a mid-luteal serum progesterone greater than 3 ng/mL
  • Nonsmokers
  • Willing to receive all study interventions
  • Physically able and willing to be randomized to participate in a supervised resistance exercise training program

Exclusion Criteria:

  • Already performing high-intensity resistance exercise training more than 1 day per week
  • On diabetes medications
  • Use of hormonal contraception in the past 3 months
  • On oral or inhaled glucocorticoids
  • Positive pregnancy test
  • Intention to become pregnant or start hormonal contraceptive therapy during the period of study
  • Lactation
  • Hypersensitivity to extrinsic peptide hormones, mannitol, Gonadotropin-releasing hormone (GnRH), leuprolide acetate, benzyl alcohol (the vehicle for injection of leuprolide acetate), or transdermal patch
  • Score greater than 16 on the Center for Epidemiologic Studies Depression Scale and Beck Depression Inventory-II score greater than 18, or clinician recommendation to exclude
  • Severe osteopenia or osteoporosis (proximal femur or lumbar spine t scores < -2.0)
  • BMI greater than 40 kg/m2, weight change of more than ± 2 kg in last 6 months, or weight-reduced by more than 5 kg from maximal body weight
  • Abnormal vaginal bleeding
  • History of breast cancer or other estrogen-dependent neoplasms
  • History of venous thromboembolic events
  • Moderate or severe renal impairment (creatinine clearance <50 mL/min by Cockcroft-Gault)
  • Chronic hepatobiliary disease, defined as liver function tests (AST, ALT, alkaline phosphatase, total bilirubin) greater than 1.5 times the upper limit of normal
  • Thyroid dysfunction, defined as ultra sensitive TSH less than 0.5 or greater than 5.0 mU/L
  • Uncontrolled hypertension, defined as resting BP greater than 150/90 mmHg
  • Cardiovascular disease, including indicators of ischemic heart disease or serious arrhythmias at rest or during the graded exercise test; follow-up diagnostic testing to rule out cardiovascular disease by a cardiologist will be allowed
  • Orthopedic or other problems that would interfere with participation in the exercise program

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 1
GnRH agonist + placebo
Drug: leuprolide acetate
3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months
Other Names:
  • Lupron
Active Comparator: 2
GnRH agonist + placebo + exercise
Drug: leuprolide acetate
3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months
Other Names:
  • Lupron
Behavioral: progressive resistance exercise training
45 minute exercise sessions 4 times per week for 5 months
Experimental: 3
GnRH agonist + Estradiol
Drug: leuprolide acetate
3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months
Other Names:
  • Lupron
Drug: Estradiol Transdermal
0.075 mg patch per day for 5 months
Other Names:
  • Climara
Experimental: 4
GnRH agonist + Estradiol + exercise
Drug: leuprolide acetate
3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months
Other Names:
  • Lupron
Behavioral: progressive resistance exercise training
45 minute exercise sessions 4 times per week for 5 months
Drug: Estradiol Transdermal
0.075 mg patch per day for 5 months
Other Names:
  • Climara

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Resting Energy Expenditure (REE)
Time Frame: Before and after 5 months of treatment
Resting energy expenditure measured by indirect calorimeter at baseline and after 5 months of treatment.
Before and after 5 months of treatment
Cortisol Response (Area Under the Curve) to CRH Under DEX Suppression
Time Frame: Before and after 5 months of treatment
Cortisol response to corticotropin releasing hormone (CRH) during dexamethasone (DEX) suppression; DEX/CRH stimulation test
Before and after 5 months of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Energy Expenditure (TEE)
Time Frame: Before and after 5 months of treatment
24-hour energy expenditure measured by indirect calorimetry in a room calorimeter
Before and after 5 months of treatment
Fat Mass
Time Frame: Before and after 5 months of treatment
Total body fat mass measured by DXA
Before and after 5 months of treatment
Fat-free Mass
Time Frame: Before and after 5 months of treatment
Total body fat-free mass measured by DXA
Before and after 5 months of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Collaborators

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Wendy M Kohrt, PhD, University of Colorado, Denver

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (Actual)

June 1, 2014

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

May 29, 2008

First Submitted That Met QC Criteria

May 29, 2008

First Posted (Estimate)

June 2, 2008

Study Record Updates

Last Update Posted (Actual)

December 9, 2019

Last Update Submitted That Met QC Criteria

November 20, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-0512
  • R01AG018198 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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