Megestrol Acetate Versus Liraglutide Plus Megestrol Acetate in Obese Women With Endometrial Atypical Hyperplasia: A Randomized Controlled Pilot Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 主要终点
- Pathological complete response (CR) rates
研究概览
简要总结
To investigate the efficacy of liraglutide plus megestrol acetate in obesity patients with atypical endometrial hyperplasia (AEH)
详细描述
Backgrounds: High-dose progesterone (MA/MPA) or LNG-IUS is the first-line treatment for women with atypical endometrial hyperplasia (AEH) or early endometrioid cancer who want to preserve fertility. About 70-80% of them can achieve complete response (CR) with the median time of 7-8 months. Over 10% of the patients can not achieve CR and choose operation finally. By the way, long-term treatment of progesterone has many side effects. Our previous study showed that overweight (BMI≥25kg/m2) AEH patients had a significantly increased risk of progesterone treatment failure, and the time to achieve CR is significantly prolonged. What's more, the greater the baseline weight of AEH patients, the greater the weight gains after high-dose progesterone treatment. Obese AEH patients have a lower response to high-dose progesterone. Weight management and lifestyle interventions are clearly written into 2020 uterine NCCN guidelines. We also find that metformin may improve insulin resistance in patients with AEH, and shorten time to achieve CR and increase the CR rates.
Liraglutide is a GLP-1 receptor agonist (GLP-1RA), which is one of the commonly used hypoglycemic drugs, has been approved for losing weight. And it is applicable for patients with BMI≥30 kg/m2 or ≥27 kg/m2 combined with one of the following: diabetes, hypertension, hyperlipidemia, sleep apnea. Liraglutide acts through improving insulin sensitivity, decreasing glucagon secretion , inhibiting appetite, delaying gastric emptying and improving whole-body inflammation condition.
Objective: To investigate whether liraglutide plus MA improve the efficacy of preserving fertility when compared to MA alone in obese women with AEH who want fertility conservation.
Design: A pilot prospective randomized controlled study is designed. And this study is open-label. We use SPSS (version 22.0,IBM) to design simple randomization. And participants will be randomly assigned (1:1) to receive MA alone or liraglutide plus MA. Patients in MA alone group will receive MA 160mg po qd and patients in the liraglutide plus MA group will receive liraglutide additionally with dose of 1.8mg/d or the max tolerance dose.
All enrolled patients will receive mentoring in weight management and lifestyle improvement. Hysteroscopic assessment will be performed every 12-16 weeks while other indexes will be evaluated every month, including weight, metabolic indications，inbody fat analysis, inflammation indicators and so on.
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
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •BMI (body mass index) ≥28kg/m2
- •Consent informed and signed
- •Pathologically confirmed as endometrial atypical hyperplasia
- •Have a strong desire to reproduce and ask for fertility preservation or those who insist on keeping the uterus despite no reproductive requirements
- •Have good compliance and follow-up conditions, and patients are willing to follow up in Obstetrics and Gynecology Hospital of Fudan University in time
排除标准
- •Diagnosed as type 2 diabetes
- •Diabetic ketoacidosis
- •History of acute pancreatitis
- •Have a history or family history of medullary thyroid carcinoma; multiple endocrine neoplasia syndrome type 2 (MEN2)
- •Combined with severe medical disease or severely impaired liver and kidney function
- •Patients with other types of endometrial cancer or other malignant tumors of the reproductive system; patients with breast cancer or other hormone-dependent tumors that cannot be used with progesterone
- •Those who require hysterectomy or other methods other than conservative treatment with drugs
- •Deep vein thrombosis, stroke, myocardial infarction
- •Smokers (≥15 cigarettes/day)
研究组 & 干预措施
MA alone
enrolled patients will receive megestrol acetate 160mg po qd
干预措施: Megestrol Acetate 160 MG (Drug)
MA+liraglutide
enrolled patients will receive megestrol acetate 160mg po qd plus liraglutide (1.8mg/d or the max tolerable dosage)
干预措施: Liraglutide Injection (Drug)
MA+liraglutide
enrolled patients will receive megestrol acetate 160mg po qd plus liraglutide (1.8mg/d or the max tolerable dosage)
干预措施: Megestrol Acetate 160 MG (Drug)
结局指标
主要结局
Pathological complete response (CR) rates
时间窗: From date of randomization until the date of CR, assessed up to 28 weeks.
The 28-week CR rates will be calculated in two groups
次要结局
- changing of insulin resistance(From date of randomization until the date of CR, assessed up to 28 weeks.)
- Time of pathological complete response (CR)(From date of randomization until the date of CR, assessed up to 2 years.)
- weight lose(From date of randomization until the date of CR, assessed up to 28 weeks)
- improvement of chronic inflammation(From date of randomization until the date of CR, assessed up to 28 weeks)
- safety and side effects(From date of randomization until the date of CR, assessed up to 2 years.)
- Relapse rates(up to 2 years after the treatment for each patient)
- pregnancy outcomes(up to 2 years after the treatment for each patient)
研究者
Xiaojun Chen
Principal Investigator
Fudan University