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Prevention of Obesity in Women Via Estradiol Regulation (POWER)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2009 by University of Colorado, Denver.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00687739
First received: May 29, 2008
Last updated: January 10, 2013
Last verified: November 2009
  Purpose

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


Condition Intervention Phase
Obesity
Drug: leuprolide acetate
Drug: Estradiol Transdermal
Behavioral: progressive resistance exercise training
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Estrogen Deficiency and Mechanisms of Fat Accumulation

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Resting Energy Expenditure (REE) Resting Metabolic Rate (RMR) [ Time Frame: Baseline, after 5 months of treatment, and 4 months post-treatment ] [ Designated as safety issue: No ]
  • DEX/CRH stimulation test (dexamethasone-suppressed CRH test)to measure stress-induced HPA axis activity [ Time Frame: Baseline, after 5 months of treatment, and 4 months post-treatment ] [ Designated as safety issue: No ]
    Cortisol response to Corticotropin Releasing Hormone under Dexamethasone suppression


Secondary Outcome Measures:
  • Energy Expenditure (EE) and Total Energy Expenditure (TEE) [ Time Frame: Baseline, 5 months of treatment, and 4 months post-treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: May 2008
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
GnRH agonist + placebo
Drug: leuprolide acetate
3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months
Other Name: 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 Name: Lupron
Behavioral: progressive resistance exercise training
45 minute exercise sessions 4 times per week for 5 months
Experimental: 3
GnRH agonist + E2
Drug: leuprolide acetate
3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months
Other Name: Lupron
Drug: Estradiol Transdermal
0.075 mg patch per day for 5 months
Other Name: Climara
Experimental: 4
GnRH agonist + E2 + exercise
Drug: leuprolide acetate
3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months
Other Name: Lupron
Drug: Estradiol Transdermal
0.075 mg patch per day for 5 months
Other Name: Climara
Behavioral: progressive resistance exercise training
45 minute exercise sessions 4 times per week for 5 months

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.

  Eligibility

Ages Eligible for Study:   18 Years to 49 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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
  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: NCT00687739

Contacts
Contact: Ellie Gibbons, BA 720-848-6408 Ellie.Gibbons@UCHSC.edu

Locations
United States, Colorado
University of Colorado Denver Recruiting
Aurora, Colorado, United States, 80045
Contact: Ellie Gibbons, BA    720-848-6408    Ellie.Gibbons@UCHSC.edu   
Principal Investigator: Wendy M Kohrt, PhD         
Sub-Investigator: Wendolyn S Gozansky, MD, MPH         
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Wendy M Kohrt, PhD University of Colorado, Denver
  More Information

Publications:
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00687739     History of Changes
Other Study ID Numbers: 06-0512, R01AG018198
Study First Received: May 29, 2008
Last Updated: January 10, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Colorado, Denver:
hormone therapy
obesity
postmenopause
disease /disorder proneness /risk
insulin sensitivity /resistance
metabolic syndrome
women's health

Additional relevant MeSH terms:
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Obesity
Body Weight
Nutrition Disorders
Overnutrition
Overweight
Signs and Symptoms
Estradiol
Estradiol 17 beta-cypionate
Estradiol 3-benzoate
Estradiol valerate
Leuprolide
Polyestradiol phosphate
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Contraceptive Agents
Contraceptive Agents, Female
Estrogens
Fertility Agents
Fertility Agents, Female
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014