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Bioenergetic Effects of Aging and Menopause (BEAM) (BEAM)

Primary Purpose

Menopause, Obesity, Abdominal, Aging

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
GnRH antagonist
Estrogen Product
Placebo estradiol
Placebo GnRH antagonist
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Menopause

Eligibility Criteria

40 Years - 65 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

Volunteers will be healthy peri/postmenopausal women who are willing and able to undergo the proposed hormone manipulation and study procedures. Women will be at least 6 months but not more than 7 years past the last menstrual period (i.e., late perimenopausal or early postmenopausal) with FSH >30 IU/L. We will make a major effort to ensure that the women enrolled in this study come from all races and ethnicities and a wide range of socioeconomic and educational levels. Women will be excluded for the reasons listed below.

Exclusion Criteria:

  • abnormal vaginal bleeding
  • on hormonal contraceptive or menopausal therapy or intention to start during the period of study
  • positive pregnancy test or intention to become pregnant during the period of study
  • lactation
  • known hypersensitivity to degarelix acetate, estradiol, or medroxyprogesterone acetate
  • Center for Epidemiological Studies Depression Scale (CES-D) score <,16 (unless clinician follow-up and clinical judgement determine they are eligible (will be noted in study chart)
  • current tobacco and/or vape use more than 2 times/week
  • current marijuana or tetrahydrocannabinol (THC) use in any form more than 3 times/week
  • regular self-reported alcohol consumption >14 drinks/week
  • BMI >39 kg/m2
  • use of glucocorticoids or drugs that affect glucocorticoid metabolism (e.g., ketoconazole)
  • severe osteopenia or osteoporosis, defined as femoral neck or lumbar spine t-score <-2.0
  • thyroid dysfunction, defined as an ultrasensitive TSH <0.5 or >5.0 mU/L; volunteers with abnormal thyroid stimulating hormone (TSH) values will be re-considered for participation in the study after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement
  • liver dysfunction, defined as liver function tests (AST, ALT) >1.5 times the upper limit of normal
  • uncontrolled hypertension defined as resting systolic BP >150 mmHg or diastolic BP>90 mmHg; participants who do not meet these criteria at first screening will be re-evaluated, including after follow-up evaluation by the primary care provider (PCP) with initiation or adjustment of anti-hypertensive medications
  • self-reported history of breast cancer or other estrogen-dependent neoplasms
  • self-reported history of venous thromboembolism, pulmonary embolism, or other thromboembolic disorder
  • self-reported history of cardiovascular disease

Sites / Locations

  • University of Colorado - Anschutz Medical CampusRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Postmenopausal: GnRH antagonist + estradiol

Postmenopausal: GnRH antagonist + placebo

Postmenopausal: placebo + placebo

Arm Description

GnRH antagonist is degarelix acetate, 80 mg, delivered twice as a subcutaneous injection (at baseline and after 12 weeks) Estradiol is a transdermal patch 0.075 mg, applied weekly for 24 weeks

GnRH antagonist is degarelix acetate, 80 mg, delivered twice as a subcutaneous injection (at baseline and after 12 weeks) Placebo is a transdermal patch, applied weekly for 24 weeks

Placebo (1) is normal saline, delivered twice as a subcutaneous injection (at baseline and after 12 weeks) Placebo (2) is a transdermal patch, applied weekly for 24 weeks

Outcomes

Primary Outcome Measures

Change in the Microdialysis Cortisone Challenge (MCC) Index
The MCC Index is an in vivo measurement of local cortisol production in abdominal adipose tissue. A higher MCC Index is an indicator of more local cortisol production.
Change in the Oral Cortisone Challenge (OCC) Area Under the Curve (AUC)
The OCC AUC is a systemic measurement of peripheral glucocorticoid metabolism. A higher OCC AUC is an indicator of more production of cortisol.

Secondary Outcome Measures

Change in lumbar spine Bone Mineral Density (BMD)
Lumbar spine BMD is measured by dual-energy x-ray absorptiometry. A higher BMD is a general indicator of less risk for osteoporosis.
Change in resting energy expenditure (REE)
REE is an index of metabolic rate at rest, measured by indirect calorimetry. A higher REE is an indicator of greater energy expenditure at rest.
Change in visceral fat area (VFA)
VFA of the abdominal visceral region is measured by computed tomography. VFA is an indicator of the amount of fat stored in this region.
Change in flow-mediated dilation (FMD)
FMD of the brachial artery as an index of vascular function. A higher number is a general indicator of better vascular function.
Change in proximal femur Bone Mineral Density (BMD)
Proximal femur BMD is measured by dual-energy x-ray absorptiometry. A higher BMD is a general indicator of less risk for osteoporosis.

Full Information

First Posted
June 25, 2019
Last Updated
October 19, 2022
Sponsor
University of Colorado, Denver
Collaborators
National Institute on Aging (NIA)
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1. Study Identification

Unique Protocol Identification Number
NCT04043520
Brief Title
Bioenergetic Effects of Aging and Menopause (BEAM)
Acronym
BEAM
Official Title
Bioenergetic and Metabolic Consequences of the Loss of Ovarian Function in Women - 2018
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 24, 2019 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
August 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
National Institute on Aging (NIA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The menopause transition is associated with increased risk for weight gain and a shift toward storing fat in the belly region, which may increase risk for cardiovascular disease and diabetes. The study will determine whether the stress hormone cortisol contributes to this shift.
Detailed Description
The menopause transition is associated with increased risk for weight gain and a shift toward storing fat in the belly region, which may increase risk for cardiovascular disease and diabetes. The stress hormone cortisol is known to promote the accumulation of belly fat, and there is evidence that low estrogen is associated with higher cortisol levels. The first aim of the study is to determine whether low estrogen levels in premenopausal and early postmenopausal women increase cortisol levels in the blood and in fat tissue. When estrogen level decreases at the time of menopause, there is an increase in follicle-stimulating hormone, or FSH. Recent evidence in mice suggests that blocking FSH prevents the increase in belly fat. The second aim of the study is to determine whether decreasing the high FSH level in postmenopausal women causes a decrease in belly fat and changes other factors that are typically thought to be related to estrogen rather than FSH. Because estrogen and FSH levels fluctuate in premenopausal and early postmenopausal women, the investigators will use an approach that controls estrogen and FSH levels to address the aims. The investigators will use a drug that is typically used to treat endometriosis or uterine fibroids to reduce estrogen and FSH levels and an estrogen patch to increase estrogen in some women. The study will generate new knowledge on how menopause affects fat gain and disease risk.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Menopause, Obesity, Abdominal, Aging, Weight Gain

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
57 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Postmenopausal: GnRH antagonist + estradiol
Arm Type
Experimental
Arm Description
GnRH antagonist is degarelix acetate, 80 mg, delivered twice as a subcutaneous injection (at baseline and after 12 weeks) Estradiol is a transdermal patch 0.075 mg, applied weekly for 24 weeks
Arm Title
Postmenopausal: GnRH antagonist + placebo
Arm Type
Experimental
Arm Description
GnRH antagonist is degarelix acetate, 80 mg, delivered twice as a subcutaneous injection (at baseline and after 12 weeks) Placebo is a transdermal patch, applied weekly for 24 weeks
Arm Title
Postmenopausal: placebo + placebo
Arm Type
Placebo Comparator
Arm Description
Placebo (1) is normal saline, delivered twice as a subcutaneous injection (at baseline and after 12 weeks) Placebo (2) is a transdermal patch, applied weekly for 24 weeks
Intervention Type
Drug
Intervention Name(s)
GnRH antagonist
Other Intervention Name(s)
Degarelix Acetate
Intervention Description
GnRH antagonist will be given once for premenopausal women (12-week intervention) and twice for postmenopausal women (24-week intervention)
Intervention Type
Drug
Intervention Name(s)
Estrogen Product
Other Intervention Name(s)
Estrogen transdermal patch
Intervention Description
Estrogen patches will be worn by those randomized to the Estradiol arms in both premenopausal and postmenopausal groups. Patches will be applied weekly and will be worn for the for entirety of the intervention (12 or 24 weeks).
Intervention Type
Drug
Intervention Name(s)
Placebo estradiol
Other Intervention Name(s)
Placebo transdermal patch
Intervention Description
Placebo patches will be worn by those randomized to the placebo arms in both premenopausal and postmenopausal groups. Patches will be applied weekly and will be worn for the for entirety of the intervention (12 or 24 weeks).
Intervention Type
Drug
Intervention Name(s)
Placebo GnRH antagonist
Other Intervention Name(s)
Placebo injection
Intervention Description
Postmenopausal women randomized to the placebo injection arm will receive two placebo drug injections of normal saline (24-week intervention)
Primary Outcome Measure Information:
Title
Change in the Microdialysis Cortisone Challenge (MCC) Index
Description
The MCC Index is an in vivo measurement of local cortisol production in abdominal adipose tissue. A higher MCC Index is an indicator of more local cortisol production.
Time Frame
Baseline, week 12
Title
Change in the Oral Cortisone Challenge (OCC) Area Under the Curve (AUC)
Description
The OCC AUC is a systemic measurement of peripheral glucocorticoid metabolism. A higher OCC AUC is an indicator of more production of cortisol.
Time Frame
Baseline, week 12
Secondary Outcome Measure Information:
Title
Change in lumbar spine Bone Mineral Density (BMD)
Description
Lumbar spine BMD is measured by dual-energy x-ray absorptiometry. A higher BMD is a general indicator of less risk for osteoporosis.
Time Frame
Baseline, week 24
Title
Change in resting energy expenditure (REE)
Description
REE is an index of metabolic rate at rest, measured by indirect calorimetry. A higher REE is an indicator of greater energy expenditure at rest.
Time Frame
Baseline, week 12, week 24
Title
Change in visceral fat area (VFA)
Description
VFA of the abdominal visceral region is measured by computed tomography. VFA is an indicator of the amount of fat stored in this region.
Time Frame
Baseline, week 24
Title
Change in flow-mediated dilation (FMD)
Description
FMD of the brachial artery as an index of vascular function. A higher number is a general indicator of better vascular function.
Time Frame
Baseline, week 12, week 24
Title
Change in proximal femur Bone Mineral Density (BMD)
Description
Proximal femur BMD is measured by dual-energy x-ray absorptiometry. A higher BMD is a general indicator of less risk for osteoporosis.
Time Frame
Baseline, week 24

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Volunteers will be healthy peri/postmenopausal women who are willing and able to undergo the proposed hormone manipulation and study procedures. Women will be at least 6 months but not more than 7 years past the last menstrual period (i.e., late perimenopausal or early postmenopausal) with FSH >30 IU/L. We will make a major effort to ensure that the women enrolled in this study come from all races and ethnicities and a wide range of socioeconomic and educational levels. Women will be excluded for the reasons listed below. Exclusion Criteria: abnormal vaginal bleeding on hormonal contraceptive or menopausal therapy or intention to start during the period of study positive pregnancy test or intention to become pregnant during the period of study lactation known hypersensitivity to degarelix acetate, estradiol, or medroxyprogesterone acetate Center for Epidemiological Studies Depression Scale (CES-D) score <,16 (unless clinician follow-up and clinical judgement determine they are eligible (will be noted in study chart) current tobacco and/or vape use more than 2 times/week current marijuana or tetrahydrocannabinol (THC) use in any form more than 3 times/week regular self-reported alcohol consumption >14 drinks/week BMI >39 kg/m2 use of glucocorticoids or drugs that affect glucocorticoid metabolism (e.g., ketoconazole) severe osteopenia or osteoporosis, defined as femoral neck or lumbar spine t-score <-2.0 thyroid dysfunction, defined as an ultrasensitive TSH <0.5 or >5.0 mU/L; volunteers with abnormal thyroid stimulating hormone (TSH) values will be re-considered for participation in the study after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement liver dysfunction, defined as liver function tests (AST, ALT) >1.5 times the upper limit of normal uncontrolled hypertension defined as resting systolic BP >150 mmHg or diastolic BP>90 mmHg; participants who do not meet these criteria at first screening will be re-evaluated, including after follow-up evaluation by the primary care provider (PCP) with initiation or adjustment of anti-hypertensive medications self-reported history of breast cancer or other estrogen-dependent neoplasms self-reported history of venous thromboembolism, pulmonary embolism, or other thromboembolic disorder self-reported history of cardiovascular disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Haley Thomas
Phone
303-724-1407
Email
haley.thomas@cuanschutz.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Ellie Gibbons
Email
ellie.gibbons@cuanschutz.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wendy M Kohrt, PhD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado - Anschutz Medical Campus
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wendy M Kohrt, PhD
Phone
303-724-1913
Email
wendy.kohrt@cuanschutz.edu
First Name & Middle Initial & Last Name & Degree
Wendy M Kohrt, PhD
First Name & Middle Initial & Last Name & Degree
Margaret Wierman, MD
First Name & Middle Initial & Last Name & Degree
Daniel Bessesen, MD
First Name & Middle Initial & Last Name & Degree
Kerrie Moreau, PhD
First Name & Middle Initial & Last Name & Degree
Edward Melanson, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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Bioenergetic Effects of Aging and Menopause (BEAM)

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