Bioenergetic Effects of Aging and Menopause (BEAM)

NCT04043520 | Unknown Phase 4 DMC FDA Drug

• 2 other identifiers: 18-2483U54AG062319
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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.

Conditions

Menopause; Obesity, Abdominal; Aging; Weight Gain

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline, week 12

• 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.

  Baseline, week 12

Secondary Outcomes (5)

• Change in lumbar spine Bone Mineral Density (BMD)

  Baseline, week 24

• Change in resting energy expenditure (REE)

  Baseline, week 12, week 24

• Change in visceral fat area (VFA)

  Baseline, week 24

• Change in flow-mediated dilation (FMD)

  Baseline, week 12, week 24

• Change in proximal femur Bone Mineral Density (BMD)

  Baseline, week 24

Study Arms (3)

Postmenopausal: GnRH antagonist + estradiol

EXPERIMENTAL

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

Drug: GnRH antagonist; Drug: Estrogen Product

Postmenopausal: GnRH antagonist + placebo

EXPERIMENTAL

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

Drug: GnRH antagonist; Drug: Placebo estradiol

Postmenopausal: placebo + placebo

PLACEBO COMPARATOR

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

Drug: Placebo estradiol; Drug: Placebo GnRH antagonist

Interventions

GnRH antagonist DRUG

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

Also known as: Degarelix Acetate

Postmenopausal: GnRH antagonist + estradiol; Postmenopausal: GnRH antagonist + placebo

Estrogen Product 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).

Also known as: Estrogen transdermal patch

Postmenopausal: GnRH antagonist + estradiol

Placebo estradiol 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).

Also known as: Placebo transdermal patch

Postmenopausal: GnRH antagonist + placebo; Postmenopausal: placebo + placebo

Placebo GnRH antagonist DRUG

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

Also known as: Placebo injection

Postmenopausal: placebo + placebo

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Colorado - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Obesity, Abdominal; Weight Gain

Interventions

LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)-; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Study Officials

• Wendy M Kohrt, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haley Thomas

CONTACT

303-724-1407; haley.thomas@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2019
• First Posted: August 2, 2019
• Study Start: September 24, 2019
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: December 18, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)