The Effect of Tirzepatide on Menopausal Vasomotor Symptoms and Biological Aging in Post-menopausal Women With Obesity

Official title

The Effect of Tirzepatide on Menopausal Vasomotor Symptoms and Biological Aging in Post-menopausal Women With Obesity: A Pilot Study

Overview

The purpose of this study is to determine the effect of tirzepatide on vasomotor symptoms and on measures of biological aging.

Interventions

• Drug Tirzepatide
  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
• Drug Placebo
  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 (c

Primary outcome measures

• Change in Vasomotor Symptoms Frequency [Time frame: Baseline, 24 weeks]
• Change in Vasomotor Symptom Severity [Time frame: Baseline, 24 weeks]
• Aging Biomarkers: Cellular Senescence Markers in Plasma [Time frame: 24 weeks]
• Difference between biological and chronological age [Time frame: 24 weeks]

Secondary outcome measures (12)

• Change in Reactive hyperemic index [Time frame: Baseline, 12 weeks and 24 weeks]
• Change in Augmentation Index percentage [Time frame: Baseline, 12 weeks, and 24 weeks]
• Change in Pulse Wave Velocity [Time frame: Baseline, 12 weeks, and 24 weeks]
• Change in Cardiometabolic Parameters: Blood Pressure [Time frame: Baseline, 24 weeks]
• Change in Cardiometabolic Parameters: Fasting Glucose [Time frame: Baseline, 24 weeks]
• Changes in Cardiometabolic Parameters: HbA1C [Time frame: Baseline, 24 weeks]
• Changes in Cardiometabolic Parameters: Lipoprotein profile [Time frame: Baseline, 24 weeks]
• Changes in Cardiometabolic Parameters: hsCRP [Time frame: Baseline, 24 weeks]
• Change in Physical Function Measure: Short Physical Performance Battery (SPPB) score. [Time frame: Baseline, 24 weeks]
• 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 [Time frame: Baseline, 24 weeks]
• Change in Physical Function Measure: Standing Chest Throw Test with a 2-kg Weighted Ball using Motion Sensor Technology (MST) [Time frame: Baseline, 24 weeks]
• Change in Physical Function Measure: Chair-to-Stand Tests using Motion Sensor Technology (MST) [Time frame: Baseline, 24 weeks]

Eligibility criteria

Inclusion criteria

• Postmenopausal women defined as 12 months of spontaneous amenorrhea, or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels > 40 mIU/ml, or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
• Age 46-60 years old.
• BMI ≥30 kg/m2 or BMI ≥27 kg/m2 in the presence of adiposity-associated diseases (hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease).
• Presence of bothersome hot flashes (≥ 28 episodes per week and of sufficient severity to prompt patients to seek therapeutic interventions).
• Hot flashes must be present for >30 days prior to study entry.
• Ability to participate in all portions of the study, including willingness to self-inject drug
• Provided informed consent to be part of the study.
• Willingness and capability to follow a hypocaloric diet, consisting of an energy deficit of approximately 500 kcal/day compared to baseline total energy expenditure, and composed of 30% from fat, 20% from protein, and 50% of carbohydrate. In addition to performing at least 150 min/week of physical activity

Exclusion criteria

• Current treatment with menopausal hormone therapy.
• Any current (past 4 weeks) or planned use of:

• Estrogen-containing contraceptive methods or menopausal hormone therapy (oral, transdermal, high dose vaginal ring, injection, pellets).
• Vaginal estrogen.
• Androgens.
• Progestogens.
• Current treatment for menopausal symptoms with cognitive behavioral therapy and/or hypnosis.
• Current use of fezolinetant.
• Menopause as a result of cancer treatments.
• Impaired renal function (GFR ≤30 ml/min/1.73 m²).
• Thyroid-stimulating hormone ≥7 with low free T4.
• 10-year ASCVD risk > 7.5%.
• Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignancy, or uncontrolled psychiatric disease.
• >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).
• Other obesity medication used within the past 3 months.
• History of bariatric surgery. Prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty performed > 1 year before screening).
• Past or intended endoscopic and/or device-based therapy or removal within last six months.
• Current or recent (within 3 months) use of medications that may cause weight gain, including tricyclic antidepressants, atypical antipsychotics, and mood stabilizers.
• Current or recent (within 3 months) use of chronic systemic glucocorticoid therapy for over 2 weeks within the past 3 months.
• 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.
• 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.
• Planned surgical procedures requiring general anesthesia or sedation during the study or within 2 weeks following the last dose of study drug.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Mayo Clinic in Florida — Jacksonville

Identifiers

NCT: NCT07218445 · 25-001692

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗