Trial record 9 of 29 for:    (menopause OR postmenopause) [CONDITION ] ((hormone therapy) OR HRT) [TREATMENT ] | Open Studies

Timing Estrogen After MenoPaUSe (TEMPUS)

This study is currently recruiting participants.
Verified November 2012 by University of Colorado, Denver
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01605071
First received: May 22, 2012
Last updated: November 20, 2012
Last verified: November 2012
  Purpose

The aim of the current study is to test whether the effect of estrogen on insulin metabolism depends on the timing of treatment relative to when a woman went through menopause. The investigators hypothesize that estrogen will improve insulin sensitivity in early postmenopausal women, but decrease insulin sensitivity in late postmenopausal women.


Condition Intervention
Insulin Resistance
Drug: Estradiol

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Official Title: TIME PAST MENOPAUSE, DURATION OF ESTROGEN DEFICIENCY, AND INSULIN ACTION

Resource links provided by NLM:


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

Primary Outcome Measures:
  • insulin-mediated glucose disposal rate (hyperinsulinemic-euglycemic clamp) [ Time Frame: after 1wk estradiol or placebo ] [ Designated as safety issue: No ]
    randomized order of testing, cross-over design


Secondary Outcome Measures:
  • fat and muscle estrogen receptor expression [ Time Frame: after 1wk estradiol or placebo ] [ Designated as safety issue: No ]
    randomized order of testing, cross-over design

  • 24hr glycemic profile (continuous glucose monitoring) [ Time Frame: after 1wk estradiol or placebo ] [ Designated as safety issue: No ]
    randomized order of testing, cross-over design


Estimated Enrollment: 60
Study Start Date: September 2011
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Early Postmenopausal
Postmenopausal women within 6 years of last menses who never used estrogen-based hormone therapy
Drug: Estradiol

1 week of transdermal estradiol (0.15mg)

1 week of transdermal placebo

Other Name: Climara
Active Comparator: Late Postmenopausal
Postmenopausal women more than 10 years since last menses who never used estrogen-based hormone therapy
Drug: Estradiol

1 week of transdermal estradiol (0.15mg)

1 week of transdermal placebo

Other Name: Climara

Detailed Description:

Large clinical trials have shown a reduced incidence of type 2 diabetes in postmenopausal women randomized to estrogen-based hormone therapy compared to placebo. Moreover, studies suggest development of diabetes is reduced in postmenopausal women who used hormone therapy for a part of the postmenopausal period compared to women who never used hormone therapy. Consistent with this, our preliminary data suggest that the timing of estrogen treatment relative to the menopause may be an important determinant of whether there are favorable effects on insulin action. Our observations suggest that estrogen improves insulin sensitivity in early postmenopausal women, but may decrease insulin sensitivity in those more than 10 years past menopause. More and more studies suggest estrogens have divergent effects on cardiovascular risk when initiated close to the onset of menopause rather than distant from the menopause; we hypothesize this is also true for diabetes risk. The goal of this study is to determine whether the effects of estrogen on insulin metabolism are different in women who are early postmenopausal compared to late postmenopausal. To meet our goal, we propose to measure insulin sensitivity in women who are within 6 years of the onset of menopause or more than 10 years beyond the menopause and who have not used hormone therapy previously. All women will be studied on two separate occasions, one day with and one day without short-term (1 week) treatment with transdermal estradiol. We expect that estradiol will increase insulin sensitivity in early postmenopausal women and decrease insulin sensitivity in late postmenopausal women. We also expect that estrogen receptors in fat and muscle may change with increasing time after menopause. Thus, we will collect fat and muscle biopsies to compare changes in estrogen receptors between early and late postmenopausal women and in response to 1 week of estradiol treatment. We believe these studies will provide evidence for a benefit of estradiol on insulin sensitivity when administered early, but not late, after menopause; likely contributing to delayed onset of type 2 diabetes in postmenopausal women.

  Eligibility

Ages Eligible for Study:   45 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • aged 45-70 yr
  • postmenopausal (no menses ≥12 mo or bilateral oophorectomy and FSH >30 IU/L)
  • ≤6yrs or ≥10yrs of menopause (last menses or oophorectomy)
  • BMI <30 kg/m2 and weight stable (±2kg in past 2mo)
  • non-smokers
  • sedentary to moderately active (<3 days/wk of structured exercise)
  • naïve to estrogen-based hormone therapies (previous use ≤6 months)
  • CBC, CMP and TSH values within normal ranges specified by lab

Exclusion Criteria:

  • underwent a partial hysterectomy (i.e., one or both ovaries left intact)
  • underwent menopause (natural, chemical, or surgical) prior to age 45yr
  • are between >6yr and <10yr of menopause (last menses or oophorectomy)
  • previously used (>6 mo) or are currently using any formulation of estrogen-based HT (e.g., oral Premarin, transdermal 17beta-estradiol, selective estrogen receptor modulators)
  • have T2DM or are being treated with glucose-lowering/ insulin sensitizing medications
  • have uncontrolled hypertension (SBP>140 and/or DBP>90 mmHg)
  • have hypertriglyceridemia (>400 mg/dL)
  • have contraindications to estrogen therapy (history of venous thromboembolism, heart disease, myocardial infarction, hormone sensitive cancer)
  • have contraindications to biopsies (severe anemia, blood clotting disorders)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01605071

Contacts
Contact: Tracy Swibas, MS 720-848-6418 tracy.swibas@ucdenver.edu

Locations
United States, Colorado
University of Colorado Denver Recruiting
Aurora, Colorado, United States, 80045
Contact: Tracy Swibas, MS    720-848-6418    tracy.swibas@ucdenver.edu   
Principal Investigator: Rachael E Van Pelt, PhD         
Sub-Investigator: Rocio Pereira, MD         
Sub-Investigator: Wendy M Kohrt, PhD         
Sub-Investigator: Teri L Hernandez, RN, PhD         
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Rachael E Van Pelt, PhD University of Colorado, Denver
  More Information

Additional Information:
Publications:
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01605071     History of Changes
Other Study ID Numbers: 11-0788, R01DK088105
Study First Received: May 22, 2012
Last Updated: November 20, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
menopause
estrogen
insulin sensitivity
estrogen receptors

Additional relevant MeSH terms:
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Estradiol
Polyestradiol phosphate
Estrogens
Estradiol valerate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Female

ClinicalTrials.gov processed this record on April 17, 2014