The Effect of Tirzepatide on Menopausal Vasomotor Symptoms and Biological Aging in Post-menopausal Women With Obesity: A Pilot Study
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in Vasomotor Symptoms Frequency
研究概览
简要总结
The purpose of this study is to determine the effect of tirzepatide on vasomotor symptoms and on measures of biological aging.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Sponsor
入排标准
- 年龄范围
- 46 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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 (an average of ≥ 28 episodes during a consecutive 2-week period with symptom severity sufficient to have prompted the participant to seek therapeutic treatment).
- •Hot flashes must be present for >30 days prior to study entry.
- •Willingness to self-inject drug
- •Provided informed consent to be part of the study.
- •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.
- •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.
排除标准
- •Current or recent use (past 4 weeks) treatment with menopausal hormone therapy.
- •Any current, recent use (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.
- •Progestogens.
- •Current or recent use (past 4 weeks) treatment for menopausal symptoms with cognitive behavioral therapy and/or hypnosis.
- •Current or recent use (past 4 weeks) of fezolinetant or elinzanetant.
- •Menopause as a result of cancer treatments.
- •Impaired renal function (GFR ≤30 ml/min/1.73 m²).
- •Thyroid-stimulating hormone ≥7 with low free T
- •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 was 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.
- •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
- •Current or recent (within 3 months) use of chronic systemic glucocorticoid therapy for over 2 weeks within the past 3 months.
- •Female who is pregnant, breastfeeding, or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.
- •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.
研究组 & 干预措施
Tirzepatide
Participants will receive tirzepatide for 24 weeks, in addition to standard lifestyle modification recommendations
干预措施: Tirzepatide (Drug)
Placebo
Participants will receive a placebo for 24 weeks, in addition to standard lifestyle modification recommendations
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Vasomotor Symptoms Frequency
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Change in Cardiometabolic Parameters: Blood Pressure(Baseline, 24 weeks)
- Change in Cardiometabolic Parameters: Fasting Glucose(Baseline, 24 weeks)
- Changes in Cardiometabolic Parameters: HbA1C(Baseline, 24 weeks)
- Changes in Cardiometabolic Parameters: Lipoprotein profile(Baseline, 24 weeks)
- Changes in Cardiometabolic Parameters: hsCRP(Baseline, 24 weeks)
- Change in Reactive hyperemic index(Baseline, 12 weeks and 24 weeks)
- Change in Augmentation Index percentage(Baseline, 12 weeks, and 24 weeks)
- Change in Pulse Wave Velocity(Baseline, 12 weeks, and 24 weeks)
- Change in Physical Function Measure: Short Physical Performance Battery (SPPB) score.(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(Baseline, 24 weeks)
- Change in Physical Function Measure: Standing Chest Throw Test with a 2-kg Weighted Ball using Motion Sensor Technology (MST)(Baseline, 24 weeks)
- Change in Physical Function Measure: Chair-to-Stand Tests using Motion Sensor Technology (MST)(Baseline, 24 weeks)
- Change in Physical Function Measure: Six-Minute Walk Test (6MWT)(Baseline, 24 weeks)
- Change in Physical Function Measure: Hand Grip Strength using a Hydraulic Hand Dynamometer(Baseline, 24 weeks)
研究者
Chrisandra L. Shufelt, MD
Principal Investigator
Mayo Clinic