ObesityPhase 3POWERNCT00687739
Prevention of Obesity in Women Via Estradiol Regulation
A Phase 3 study testing leuprolide acetate, Estradiol Transdermal and progressive resistance exercise training in people with Obesity, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The purpose of this study is to evaluate potential mechanisms by which estradiol deficiency accelerates fat gain and abdominal fat accumulation in women. Read more about this study
- Who is it for?
- Ages 18 to 49 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- leuprolide acetate, Estradiol Transdermal and progressive resistance exercise training
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 79 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Jun 2014
- Phase
- Phase 3
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 18 to 49 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: 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.
Read the 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.
- Conditions
- Obesity
- Being tested
- leuprolide acetate, Estradiol Transdermal, progressive resistance exercise training
- Keywords
- hormone therapy, obesity, postmenopause, disease /disorder proneness /risk, insulin sensitivity /resistance, metabolic syndrome, women's health
- Medical subject headings
- Obesity, Disease Susceptibility, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
leuprolide acetateDrug
Also called Lupron
3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months
Estradiol TransdermalDrug
Also called Climara
0.075 mg patch per day for 5 months
progressive resistance exercise trainingBehavioural
45 minute exercise sessions 4 times per week for 5 months
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | GnRH agonist + placebo Receives: Drug: leuprolide acetate |
| 2 | Active comparator | GnRH agonist + placebo + exercise Receives: Drug: leuprolide acetate; Behavioral: progressive resistance exercise training |
| 3 | Experimental | GnRH agonist + Estradiol Receives: Drug: leuprolide acetate; Drug: Estradiol Transdermal |
| 4 | Experimental | GnRH agonist + Estradiol + exercise Receives: Drug: leuprolide acetate; Drug: Estradiol Transdermal; Behavioral: progressive resistance exercise training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resting Energy Expenditure (REE)
Resting energy expenditure measured by indirect calorimeter at baseline and after 5 months of treatment.
Measured: Before and after 5 months of treatment
Cortisol Response (Area Under the Curve) to CRH Under DEX Suppression
Cortisol response to corticotropin releasing hormone (CRH) during dexamethasone (DEX) suppression; DEX/CRH stimulation test
Measured: Before and after 5 months of treatment
Secondary outcomes (3)
Total Energy Expenditure (TEE)
24-hour energy expenditure measured by indirect calorimetry in a room calorimeter
Measured: Before and after 5 months of treatment
Fat Mass
Total body fat mass measured by DXA
Measured: Before and after 5 months of treatment
Fat-free Mass
Total body fat-free mass measured by DXA
Measured: Before and after 5 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2008 (estimated)
- Study startMay 2008
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Wendy M Kohrt, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00687739
- Sponsor's protocol ID
- 06-0512
- Other IDs
- R01AG018198
- Acronym
- POWER
- Status last verified
- Mar 2025
- First submitted
- 29 May 2008
- Last updated
- 1 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O'Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S; Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004 Apr 14;291(14):1701-12. doi: 10.1001/jama.291.14.1701.
PubMed 15082697Sites CK, L'Hommedieu GD, Toth MJ, Brochu M, Cooper BC, Fairhurst PA. The effect of hormone replacement therapy on body composition, body fat distribution, and insulin sensitivity in menopausal women: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2005 May;90(5):2701-7. doi: 10.1210/jc.2004-1479. Epub 2005 Feb 1.
PubMed 15687338Utian WH, Gass ML, Pickar JH. Body mass index does not influence response to treatment, nor does body weight change with lower doses of conjugated estrogens and medroxyprogesterone acetate in early postmenopausal women. Menopause. 2004 May-Jun;11(3):306-14. doi: 10.1097/01.gme.0000117062.54779.bd.
PubMed 15167310Gavin KM, Shea KL, Gibbons E, Wolfe P, Schwartz RS, Wierman ME, Kohrt WM. Gonadotropin-releasing hormone agonist in premenopausal women does not alter hypothalamic-pituitary-adrenal axis response to corticotropin-releasing hormone. Am J Physiol Endocrinol Metab. 2018 Aug 1;315(2):E316-E325. doi: 10.1152/ajpendo.00221.2017. Epub 2018 Apr 6.
PubMed 29631362