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临床试验/NCT03573063
NCT03573063已完成不适用

Starvation Effect on Androgen Metabolism in Healthy Young Women.

Insel Gruppe AG, University Hospital Bern2 个研究点 分布在 1 个国家目标入组 20 人开始时间: 2018年10月26日最近更新:
适应症
干预措施

试验速览

阶段
不适用
状态
已完成
入组人数
20
试验地点
2
主要终点
The primary outcome is changes in androgen metabolism. The evaluation will compare the steroid concentrations at the three time points with uni- and multivariate data analysis to detect fasting-related differences.

研究概览

简要总结

In this study, the investigators wanted to investigate the energy homeostasis and the steroid metabolism of 20 healthy, young and normal weight women aged between 16-35 years before and after a 48 hours fasting period.

The following substrates and hormone concentrations representing the carbohydrate, fat and protein metabolism will be measured from plasma or urine before and after fasting: glucose, insulin, lactate, alpha-synucleine, free fatty acids, beta-hydroxybutyrate (ketone bodies), carnitine (surrogate for acetyl-CoA) and alanine (amino acids). In addition, the investigators will measure 67 steroid metabolites by GC/MS and Biokrates AbsolutIDQ Steroid Assay in all collected urines and blood samples.

In the analysis of the data, the investigators will focus on correlations between biochemical parameters of the energy metabolism and parameters of the steroid metabolism, specifically the androgens. In addition, the steroid profiles obtained from healthy young women before and after fasting will be compared to steroid profiles of PCOS women in search for specific differences.

详细描述

The first aim of this study is to investigate the energy homeostasis and the steroid metabolism of healthy, young and normal weight women aged 16-35 years, before and after a 48 hours fasting period. Furthermore, second aim of this study is the comparison of their steroid profiles with PCOS women in search for specific differences.

In fact it might be therefore hypothesized that the energy metabolism in PCOS women functions like under (glucose) starvation conditions. In a pilot experiment performed in a healthy young women of normal weight, the investigators observed that short term starvation over 48 hours changed her steroid profile from normal to PCOS-like with elevated testosterone with elevated testosterone, DHT and androsterone/etiocholanolone ratio. It has been suggested that during normal fasting and feeding metabolic signals such as AMP/NAD+ and acetyl-CoA translate the energy state into specific metabolic programs. The investigators suggest that androgen biosynthesis might be one of these programs. Therefore, becoming hyperandrogenic during short term starvation might be normal, and the regulation between energy balance and androgen biosynthesis might be visible in healthy subjects, thereby hinting pathways leading to PCOS and better treatment options.

In this study the investigators will recruit 20 healthy, normal weight women aged 16-35 years with regular cycle and without drug treatment, including hormonal contraception. Characteristics of the participant and written informed consent with the study will be collected. The study will start 14-21 days after the last menstrual period of the participant. Twenty-four hours prior the first study visit the participant will collect a 24 hours urine sample and a spot urine.

On day one of the study, the participant will come early morning for the first visit to the Inselspital Bern. The participant will be informed again and the exact study protocol will be explained to make sure the participant is willing to fulfil the study requirements. The investigators will draw blood, perform a pregnancy test and collect the 24 hours urine as well as a spot urine. At this point the starvation period will start (=intake to a maximum of 500-800 kcal/d for 24 hours, depends on the weight of the participant). A dietary plan is provided by Mrs. T. Zürcher, Pediatric Dietician, Childrens' Hosp. Inselspital Berne.

This regimen is selected on the basis that the human body switches into a state of "hunger" and starts to burn fat instead of glucose after about 12 hours. During a 48 hours fasting period the metabolism changes dramatically. During this state hormonal and chemical changes will be investigated in blood and urine samples. During the starvation the participants have to stick strictly to the dietary restriction regimen, which they will monitor themselves. If the participants fails to do so, they will be excluded from continuation of the study and cannot participate a second time. Fasting state and thus compliance are visible in the measured lab data (e.g. ketone bodies).

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Basic Science
盲法
None

入排标准

年龄范围
16 Years 至 35 Years(Child, Adult)
性别
Female
接受健康志愿者

入选标准

  • Aged 16-35
  • Normal weight
  • Postpubertal
  • No drug treatments (including oral/hormonal anticonception)
  • Informed consent

排除标准

  • Hormone treatment (i.e.: hormonal contraception, cortisol)
  • Hormone disorders
  • Infertile
  • Chronic diseases

研究组 & 干预措施

Androgen metabolism after starvation

Other

Metabolism changes after 48 hours starvation in healthy women

干预措施: Androgen metabolism after starvation (Other)

结局指标

主要结局

The primary outcome is changes in androgen metabolism. The evaluation will compare the steroid concentrations at the three time points with uni- and multivariate data analysis to detect fasting-related differences.

时间窗: One year

With GC/MS (urine) and LCMSMS (blood) 40 steroids in urine (ug/24h) and 18 steroids in serum (pg/ml or nmol/L) (Biokrates) will be measured; these includes Progesterones, Androgens, Estrogens, Corticosterones, Mineralocorticoids, Glucocorticoids. Other markers consist of glucose (mmol/L), potassium (mmol/L), insulin (mU/L), lactate (mmol/L), free fatty acids (umol/L), ketone-bodies (beta-hydroxy-butyrate), carnitin, alanin - all umol/L). All parameters will be analysed in the laboratories of the Institute of Clinical Chemistry and Steroid Laboratory of Nephrology of Inselspital. For more details please see list in Appendices of the Clinical Study Protocol (Page 38-41). All data are assessed as absolute values and follow-up is studied for changes in values rather than for normative values, which mostly do not exist for fasting intervention.

次要结局

  • Steroid profiles(One year)

研究者

申办方类型
Other
责任方
Sponsor

研究点 (2)

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