Treating PCOS With Semaglutide vs Active Lifestyle Intervention
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Change in Hepatic Fat Fraction
研究概览
简要总结
Girls with obesity and polycystic ovarian syndrome will receive either glucagon like peptide-1 receptor agonist therapy or a dietary intervention for 12 weeks to decrease the metabolic syndrome, in particular to lower hepatic fat and improve insulin sensitivity.
详细描述
In obese girls with polycystic ovarian syndrome, testosterone and obesity combine to create unique pathology to increase metabolic disease including fatty liver and insulin resistance, which may be mediated by altered glucagon like peptide-1 activity. The investigators will treat girls with obesity and polycystic ovarian syndrome for 4 months with a glucagon like peptide-1 receptor agonist compared to dietary intervention to primarily lower hepatic fat and secondarily improve whole body and adipose insulin sensitivity. Mechanisms of hepatic metabolism, including rates of de novo lipogenesis and relative mitochondrial flux will also be assessed.
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
- 12 Years 至 21 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Sedentary- less than 2 hours of moderate (jogging, swimming etc) exercise a week.
- •BMI equal or greater than the 90th percentile for age and gender
- •PCOS per the most stringent NIH criteria adapted for adolescents (irregular menses >12 months post-menarche and clinical or biochemical hypertestosteronemia
- •Participants cannot be on hormonal contraception, so participants should remain abstinent or use reliable non-hormonal contraception (e.g. copper IUD) for the entire study period. For participants who receive semaglutide, they should avoid pregnancy for at least 2 months after stopping medication to avoid fetal exposure to the medication.
排除标准
- •Diagnosed with or have a family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Family history of medullary thyroid cancer or thyroid nodule palpated by endocrinologist at screening.
- •Use of medications known to affect insulin sensitivity: metformin (cannot have been used in the 3 months prior to screening), oral glucocorticoids within 10 days, atypical antipsychotics, immunosuppressant agents, HIV medications, hormonal contraception (cannot have been used in the 6 months prior to screening). Dermal patch or vaginal ring contraception methods.Weight loss medications or stimulants. Use of other products containing other GLP-1 agonists.
- •Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.
- •Severe illness requiring hospitalization within 60 days.
- •Diabetes, defined as Hemoglobin A1C > 6.4%
- •BMI percentile less than the 90th percentile for age and sex. Weight >325 lbs. or <84 lbs.
- •Anemia, defined as Hemoglobin < 11 mg/dL
- •Diagnosed major psychiatric or developmental disorder limiting informed consent.
- •Implanted metal devices that are not compatible with MRI
- •Use of blood pressure medications.
- •Known liver disease other than NAFLD or AST or ALT >100 IU/L.
- •Personal history of pancreatitis
- •Known renal disease of any severity or an eGFR at screening of <45ml/min/1.73m2
- •History of severe GI disease (e.g. gastroparesis)
- •History of gallstones
- •Untreated thyroid disease
- •History of hypersensitivity to semaglutide
- •Other causes of hyperandrogenism (example: tumor, CAH) or amenorrhea (untreated thyroid disease, tumor, primary ovarian failure, prolactinoma).
- •Active symptoms or undergoing treatment for anorexia nervosa or binging/purging disorder
研究组 & 干预措施
Diet Intervention
Weight loss with dietary intervention
干预措施: Weight loss diet (Other)
GLP-1 Intervention
Participants will take a daily oral tablet of semaglutide for 4 months.
干预措施: Semaglutide 3mg and 7mg [Rybelsus] (Drug)
结局指标
主要结局
Change in Hepatic Fat Fraction
时间窗: Baseline and 12 weeks
Change from baseline in presence/severity of hepatic fat fraction will be measured with MRI, and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%. A negative value means a decrease in liver fat, and a positive value means an increase in liver fat.
Change in Weight
时间窗: Baseline and 12 weeks
Change in weight will be calculated for each group (diet and semaglutide), and both the absolute and relative weight changes between the two groups will be reported.
次要结局
- Change in Rate of De Novo Lipogenesis (DNL)(Baseline and 12 weeks)
- Change in Whole Body Insulin Sensitivity(Baseline and 12 weeks)
- Change in Adipose Insulin Sensitivity(Baseline and 12 weeks)