Menopause Hot Flashes, Obesity
Conditions
Keywords
Hot flashes, menopause, Tirzepatide, GLP
Brief summary
The purpose of this study is to determine the effect of tirzepatide on vasomotor symptoms and on measures of biological aging.
Interventions
DRUGTirzepatide
Tirzepatide will be administered with a starting dose of 2.5 mg weekly, subcutaneously injected. The dose will increase by 2.5 mg every 4 weeks until reaching 15 mg. Participants will be asked to follow lifestyle interventions: * Low-calorie diet based on their predicted by Harris Benedict resting energy expenditure minus 500 kcal per day * Physical activity: a goal of 10,000 steps or more per day * Exercise: a goal of 150 minutes or more of moderate-intensity aerobic activity (cardiovascular exercise) per week * Limited consumption of liquid calories (i.e. sodas, juices, alcohol, etc.).
DRUGPlacebo
A placebo for Tirzepatide will be administered with a starting dose of 2.5 mg weekly, subcutaneously injected. The dose will increase by 2.5 mg every 4 weeks until reaching 15 mg. Participants will be asked to follow lifestyle interventions: * Low-calorie diet based on their predicted by Harris Benedict resting energy expenditure minus 500 kcal per day * Physical activity: a goal of 10,000 steps or more per day * Exercise: a goal of 150 minutes or more of moderate-intensity aerobic activity (cardiovascular exercise) per week * Limited consumption of liquid calories (i.e. sodas, juices, alcohol, etc.).
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor
Eligibility
Sex/Gender
FEMALE
Age
46 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Females 2. Age 46-60 years old. 3. BMI ≥30 kg/m2 or BMI ≥27 kg/m2 in the presence of adiposity-associated diseases (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease). 4. Presence of bothersome hot flashes (an average of ≥ 28 episodes during a consecutive 2-week period with symptom severity sufficient to have prompted the participant to seek therapeutic treatment). 5. Hot flashes must be present for \>30 days prior to study entry. 6. Willingness to self-inject drug 7. Provided informed consent to be part of the study. 8. Willingness and capability to follow an individualized hypocaloric diet designed to achieve an approximate energy deficit of 500 kcal/day relative to estimated total daily energy requirements. Daily energy requirements will be calculated using Harris-Benedict equation to estimate resting energy expenditure and multiplied by a sedentary physical activity factor of 1.2. Prescribed daily caloric intake will not be less than 1,000 kcal/day. Participants must also be willing to engage in at least 150 minutes per week of moderate-intensity or greater physical activity.
Exclusion criteria
1. Current or recent use (past 4 weeks) treatment with menopausal hormone therapy. 2. Any current, recent use (past 4 weeks), or planned use of: 1. Estrogen-containing contraceptive methods or menopausal hormone therapy (oral, transdermal, high dose vaginal ring, injection, pellets). 2. Vaginal estrogen. 3. Androgens. 4. Progestogens. 3. Current or recent use (past 4 weeks) treatment for menopausal symptoms with cognitive behavioral therapy and/or hypnosis. 4. Current or recent use (past 4 weeks) of fezolinetant or elinzanetant. 5. Menopause as a result of cancer treatments. 6. Impaired renal function (GFR ≤30 ml/min/1.73 m²). 7. Thyroid-stimulating hormone ≥7 with low free T4. 8. 10-year ASCVD risk \> 7.5%. 9. Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignancy, or uncontrolled psychiatric disease. 10. \>5% change in weight during the 3 months prior to screening and, or eight fluctuation of ≥20 pounds within the past 6 months (self-report). 11. Other obesity medication was used within the past 3 months. 12. History of bariatric surgery. Prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty performed \> 1 year before screening). 13. Past or intended endoscopic and/or device-based therapy or removal within last six months. 14. Use of weight gain-promoting medications (including tricyclic antidepressants, atypical antipsychotics, and mood stabilizers), unless the participant has been receiving the medication at a stable dose for ≥3 months prior to enrollment and has maintained a stable body weight during that time 15. Current or recent (within 3 months) use of chronic systemic glucocorticoid therapy for over 2 weeks within the past 3 months. 16. Female who is pregnant, breastfeeding, or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method. 17. Contraindications to GLP-1 receptor agonist therapy as per Tirzepatide (Zepbound ®) label, including a personal or family history of medullary thyroid carcinoma; a history or diagnosis of multiple endocrine neoplasia syndrome type 2; known hypersensitivity to tirzepatide or any of its excipients. 18. Currently enrolled in another clinical study involving an investigational product or participated in one and received treatment (active or placebo) in the last 30 days. 19. Planned surgical procedures requiring general anesthesia or sedation during the study or within 2 weeks following the last dose of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Vasomotor Symptoms Frequency | Baseline, 24 weeks | Change in the frequency of self-reported daily average vasomotor symptoms from baseline to 24 weeks. Vasomotor symptoms will be captured for 2 weeks at baseline and 2 weeks at the end of the study. |
| Change in Vasomotor Symptom Severity | Baseline, 24 weeks | Change in self-reported daily vasomotor symptom severity from baseline to 24 weeks. Vasomotor symptoms will be captured for 2 weeks at baseline and at the end of the study. Severity will be classified as follows: Mild, sensation of heat without sweating/dampness; Moderate: sensation of heat with sweating/dampness, but able to continue current activity. May briefly fan yourself; Severe: sensation of intense heat with sweating causing disruption of current activity. |
| Aging Biomarkers: Cellular Senescence Markers in Plasma | 24 weeks | Cellular senescence markers are measured in plasma samples to assess biological aging and cellular stress. These markers may include proteins associated with the senescence-associated secretory phenotype (SASP). Quantification is performed using immunoassays. Higher levels of senescence markers indicate increased cellular senescence. |
| Difference between biological and chronological age | 24 weeks | Epigenetic clocks estimate biological age by analyzing DNA methylation patterns at specific CpG sites across the genome. Biological age estimates are compared to chronological age to assess aging acceleration or deceleration. Biological age greater than chronological age indicates accelerated biological aging and potential increased risk of morbidity and mortality. Primary measure is the difference (ΔAge) between biological and chronological ages = reported in years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Reactive hyperemic index | Baseline, 12 weeks and 24 weeks | Vascular function will be measured using the EndoPAT device to assesses reactive hyperemia index (RHI) from baseline to week 24 on treatment or placebo. RHI is automatically calculated through a computer algorithm by following the equation: \[(tested arm-post occlusion/tested arm-baseline)/(control arm-post occlusion/control arm-baseline)\] × baseline correction factor. Endothelial dysfunction is defined as having an RHI ratio of equal or less than 1.67. |
| Change in Augmentation Index percentage | Baseline, 12 weeks, and 24 weeks | Augmentation Index (AIx): AIX uses applanation tonometry of the radial artery pulse, calibrated to resting brachial systolic and diastolic pressures (SphygmoCor XCEL, Medtronic, Minneapolis, MN). Aortic systolic, diastolic, and pulse pressures will be derived from a synthesized aortic waveform using a validated mathematical transfer function. Augmentation pressure, reflecting the difference between aortic systolic pressure and the inflection point caused by the reflected wave, is influenced by arterial stiffness as well as factors like heart rate and ejection dynamics. AIx is calculated as augmentation pressure divided by aortic pulse pressure × 100%, adjusted to a heart rate of 75 bpm (AIx@75 bpm). Measurements will be performed in duplicate and averaged. |
| Change in Pulse Wave Velocity | Baseline, 12 weeks, and 24 weeks | SphygmoCor estimates central arterial stiffness by calculating the speed at which the pressure wave travels between the carotid and femoral arteries using applanation tonometry and reported as the pulse wave velocity (PWV); PWV m/s |
| Change in Cardiometabolic Parameters: Blood Pressure | Baseline, 24 weeks | Change in cardiometabolic parameters including blood pressure from baseline to week 24 on treatment or placebo. Measured in mmhg |
| Change in Cardiometabolic Parameters: Fasting Glucose | Baseline, 24 weeks | Change in cardiometabolic parameters including fasting glucose from baseline to week 24 on treatment or placebo. Measured in mg/dL |
| Changes in Cardiometabolic Parameters: HbA1C | Baseline, 24 weeks | Change in cardiometabolic parameters including HbA1C from baseline to week 24 on treatment or placebo. Measured in % |
| Changes in Cardiometabolic Parameters: Lipoprotein profile | Baseline, 24 weeks | Change in cardiometabolic parameters including Lipoprotein profile from baseline to week 24 on treatment or placebo. Measured in mg/dL |
| Changes in Cardiometabolic Parameters: hsCRP | Baseline, 24 weeks | Change in cardiometabolic parameters including hsCRP from baseline to week 24 on treatment or placebo. Measured in mg/L |
| Change in Physical Function Measure: Short Physical Performance Battery (SPPB) score. | Baseline, 24 weeks | The SPPB is a standardized test that evaluates lower extremity function using three components: balance tests (standing in various positions), gait speed (walking a short distance), and chair stand (repeated standing from a seated position). Each component is scored from 0 to 4; the total score ranges from 0 to 12. Higher scores represent better physical function |
| Change in Physical Function Measure: Modified Clinical Test of Sensory Interaction in Balance (mCTSIB) performed on the Rehabilitation Artificial Physical Intelligence Database (RAPID) foot pressure mat | Baseline, 24 weeks | The mCTSIB assesses balance under four sensory conditions: eyes open/closed on firm and foam surfaces. Testing is performed while standing on the RAPID foot pressure mat, which captures center of pressure and postural sway data. The primary measure is average sway area of the four sensory conditions. The sway area is the area which is required to correct equilibrium, representing the total area covered by postural sway, measured in square centimeters (cm²). |
| Change in Physical Function Measure: Standing Chest Throw Test with a 2-kg Weighted Ball using Motion Sensor Technology (MST) | Baseline, 24 weeks | This test evaluates upper body muscular power. Participants perform a two-handed chest throw of a 2-kg medicine ball from a standing position. The MST is used to record throw distance, velocity, and related performance metrics. The primary measure is Peak Power Score (W). |
| Change in Physical Function Measure: Chair-to-Stand Tests using Motion Sensor Technology (MST) | Baseline, 24 weeks | This test assesses lower body strength and function. Participants are instructed to stand up from a chair and sit back down five times without using their arms. The MST measures movement dynamics. The primary measure is peak power score (W). |
| Change in Physical Function Measure: Six-Minute Walk Test (6MWT) | Baseline, 24 weeks | The 6MWT is a standardized submaximal exercise test used to assess functional aerobic capacity. Participants are instructed to walk as far as possible in six minutes along a flat, straight course. The total distance walked is recorded in feet. Longer walking distances indicate better aerobic capacity and endurance. |
| Change in Physical Function Measure: Hand Grip Strength using a Hydraulic Hand Dynamometer | Baseline, 24 weeks | Participants are instructed to squeeze the dynamometer with maximum effort, measured in kilograms. The highest value from multiple trials is recorded. |
Countries
United States
Contacts
CONTACTTina Taaffe
CONTACTLauren Uy
PRINCIPAL_INVESTIGATORChrisandra Shufelt, MD
Mayo Clinic
Outcome results
None listed