Bioenergetic Effects of Aging and Menopause (BEAM)

NCT ID: NCT04043520

Last Updated: 2023-12-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-24
• Study Completion Date: 2024-08-31

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.

Conditions

Menopause; Obesity, Abdominal; Aging; Weight Gain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Postmenopausal: GnRH antagonist + estradiol

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

Group Type: EXPERIMENTAL

GnRH antagonist

Intervention Type: DRUG

GnRH antagonist will be given once for premenopausal women (12-week intervention) and twice for postmenopausal women (24-week intervention)

Estrogen Product

Intervention Type: DRUG

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).

Postmenopausal: GnRH antagonist + placebo

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

Group Type: EXPERIMENTAL

GnRH antagonist

Intervention Type: DRUG

GnRH antagonist will be given once for premenopausal women (12-week intervention) and twice for postmenopausal women (24-week intervention)

Placebo estradiol

Intervention Type: DRUG

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).

Postmenopausal: placebo + placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo estradiol

Intervention Type: DRUG

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).

Placebo GnRH antagonist

Intervention Type: DRUG

Postmenopausal women randomized to the placebo injection arm will receive two placebo drug injections of normal saline (24-week intervention)

Interventions

GnRH antagonist

GnRH antagonist will be given once for premenopausal women (12-week intervention) and twice for postmenopausal women (24-week intervention)

Intervention Type: DRUG

Estrogen Product

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

Placebo estradiol

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

Placebo GnRH antagonist

Postmenopausal women randomized to the placebo injection arm will receive two placebo drug injections of normal saline (24-week intervention)

Intervention Type: DRUG

Other Intervention Names

Degarelix Acetate; Estrogen transdermal patch; Placebo transdermal patch; Placebo injection

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wendy M Kohrt, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado - Anschutz Medical Campus

Aurora, Colorado, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Haley Thomas

Role: CONTACT

Phone: 303-724-1407

Email: haley.thomas@cuanschutz.edu

Facility Contacts

Wendy M Kohrt, PhD

Role: primary

Other Identifiers

U54AG062319

Identifier Type: NIH

Identifier Source: secondary_id

View Link

18-2483

Identifier Type: -

Identifier Source: org_study_id