A Metabolomic Study of Polycystic Ovary Syndrome With Insulin Resistance and Its Relationship With TCM Syndrome Types

PCOS Clinical Trial

Official title:

Fujian Maternity and Child Health Hospital

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02992093
• Other study ID #: Dunjingjing
• Status: Not yet recruiting
• Phase: N/A
• First received: December 1, 2016
• Last updated: December 14, 2016
• Start date: December 2016
• Est. completion date: August 2020

Study information

• Verified date: December 2016
• Source: Fujian Maternity and Child Health Hospital
• Contact: Jinbang Xu
• Phone: 13559958096
• Email: 13559958096[@]126.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Observational

Clinical Trial Summary

The type-2 diabetes mellitus（T2DM）, metabolic syndrome, cardiovascular disease complications induced by polycystic ovary syndrome(PCOS) with insulin resistance(IR）, which become serious threat to public health. In this observational study, obese patients with PCOS,nonobese patients with PCOS, PCOS patients with impaired glucose tolerance（IGT）, PCOS patients with type-2 diabetes mellitus（T2DM）, and healthy volunteers would enrolled into this study, through the Liquid Chromatography-Mass Spectrometry coupled to Mass Spectrometry（ LC-MS/MS）and Rapid Resolution Liquid Chromatography（RRLC） and Quadrupole Linear Trap（QTRAP）Mass Spectrometry coupled to Mass Spectrometry （MS/MS）analysis of serum samples collected from PCOS patients and healthy volunteers to screen the biomarker of diagnosis for PCOS with insulin resistance, to explore the correlation between traditional chinese medicine （TCM） syndrome（phlegm, kidney yin deficiency, kidney yang deficiency, qi stagnation and blood stasis，dampness-heat of liver channel）and metabolites of PCOS.

Description:

1. The selection of research subjects: All the subjects collect from Fujian Maternity and Child Health Hospital.

2. The participants will be divided into five groups：obese with PCOS，nonobese with PCOS，PCOS with IGT，PCOS with T2DM，healthy volunteers.the syndrome type of PCOS will be divided into five types: phlegm, kidney yin deficiency, kidney yang deficiency, liver qi stagnation and blood stasis syndrome, dampness-heat of liver channel.

3. Ethical requirements and subjects' informed consent Before clinical trials begin, the program needs to be approved by the ethics committee to approve and sign the approval.The subjects need fully aware of the clinical trial and are given sufficient time to consider whether they are willing to participate in the trial, and to sign the informed consent form.

4. Indicator test (the cost of all health volunteers are paid by the research) (1)Physical examination: blood pressure, height, body weight,waist circumference,hip circumference，body mass index(BMI),waist-hip ratio（WHR）.

(2)Endocrine hormones: collect serum from all the subjects，use the enzyme linked immunosorbent assay (ELISA) method to detect the level of serum follicle-stimulating hormone（FSH）,luteinizing hormone（LH）,prolactin（PRL）,estradiol（E2）,testosterone（T）. Blood lipid: glycerin three vinegar (TG), cholesterol (CHOL) detect by enzymatic method, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) detect by the turbidity method. Glucose tolerance and insulin release test after glucose loading: all subjects were fasting for 8 to 10 h, check the fasting blood glucose(FBG)and fasting insulin （FINS）.The oral glucose tolerance test（OGTT）and insulin release test were performed in the next morning.

5.Study on the characteristics of metabolism

（1）Through the sample pretreatment method, analyzes the optimization of the condition of mass spectrometry, according to the requirements of the metabolism to establish the blood sample LC-MS/MS metabolism analysis method.（2）Carry out the analysis of metabolism and data collection.（3）Model building and data analysis（4）Use RRLC and QTRAP type MS/MS with positive and negative ion detection mode with the combination of hyphenated techniques, combined with the method of data statistics,to establish multiple reaction monitoring（MRM） detection, to verify the precision and sensitivity of the method.

6.Statistical methods: All data use statistical product and service solutions18.0（SPSS18.0）software package for statistical analysis. According to the character of clinical trial data (measurement, classification and grade data), select the appropriate statistical analysis method.receiver operating characteristic curve（ROC） analysis of the potential metabolites selected from the targeting metabolic biomarker.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: August 2020
• Est. primary completion date: May 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

1. The diagnosis of polycystic ovary syndrome (PCOS) according to the Rotterdam consensus criteria recommended by European Society of Human Reproduction and Embryology and American Society for Reproductive Medicine in 2003(2 out of 3):Oligo-and/or anovulation;Clinical and/or biochemical signs of hyperandrogenism;Polycystic ovaries.

2. Diagnostic criteria for insulin resistance: use the HOMA model to evaluate insulin resistance. The HOMA index of insulin resistance (HOMA-IR) = (fasting blood glucose (mmol/L)× fasting insulin (mIU/L) /22.5.

3. voluntary subjects

Exclusion Criteria:

1. the exclusion of other causes of Kaohsiung hormones, such as congenital adrenal hyperplasia, Cushing syndrome, androgen secreting tumors, and other diseases caused by ovulation disorders, such as hyperprolactinemia, premature ovarian failure, pituitary or hypothalamus closed by etc;

2. exclusion of organic disease or other endocrine diseases;

3. with liver and kidney, cerebral blood vessels, cardiovascular and hematopoietic disorders, such as primary disease, mental patients;

4. patients who had been treated with steroids in nearly three months , such as the birth control pill, and corticosteroids.

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• PCOS
• Polycystic Ovary Syndrome

Intervention

Other:
• all the indicators
BMI?WHR?FSH?LH?PRL?T?E2?TG?CHOL?LDL-C?HDL-C?FBG?OGTT?FINS?insulin release test?HOMA index?identification of metabolites

Locations

Country	Name	City	State
China	Fujian Maternity and Child Health Hosptial	Fuzhou	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
Fujian Maternity and Child Health Hospital

Country where clinical trial is conducted

China, 

References & Publications (14)

Atiomo W, Daykin CA. Metabolomic biomarkers in women with polycystic ovary syndrome: a pilot study. Mol Hum Reprod. 2012 Nov;18(11):546-53. doi: 10.1093/molehr/gas029. — View Citation

Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society.. The An — View Citation

Chen L, Xu WM, Zhang D. Association of abdominal obesity, insulin resistance, and oxidative stress in adipose tissue in women with polycystic ovary syndrome. Fertil Steril. 2014 Oct;102(4):1167-1174.e4. doi: 10.1016/j.fertnstert.2014.06.027. Erratum in: F — View Citation

Collins FS, Green ED, Guttmacher AE, Guyer MS; US National Human Genome Research Institute.. A vision for the future of genomics research. Nature. 2003 Apr 24;422(6934):835-47. — View Citation

Escobar-Morreale HF, Samino S, Insenser M, Vinaixa M, Luque-Ramírez M, Lasunción MA, Correig X. Metabolic heterogeneity in polycystic ovary syndrome is determined by obesity: plasma metabolomic approach using GC-MS. Clin Chem. 2012 Jun;58(6):999-1009. doi — View Citation

Gaster M, Nehlin JO, Minet AD. Impaired TCA cycle flux in mitochondria in skeletal muscle from type 2 diabetic subjects: marker or maker of the diabetic phenotype? Arch Physiol Biochem. 2012 Jul;118(3):156-89. doi: 10.3109/13813455.2012.656653. Review. — View Citation

Sathyapalan T, Atkin SL. Recent advances in cardiovascular aspects of polycystic ovary syndrome. Eur J Endocrinol. 2012 Apr;166(4):575-83. doi: 10.1530/EJE-11-0755. Review. — View Citation

Sun L, Hu W, Liu Q, Hao Q, Sun B, Zhang Q, Mao S, Qiao J, Yan X. Metabonomics reveals plasma metabolic changes and inflammatory marker in polycystic ovary syndrome patients. J Proteome Res. 2012 May 4;11(5):2937-46. doi: 10.1021/pr3000317. — View Citation

Suvarna Y, Maity N, Kalra P, Shivamurthy MC. Comparison of efficacy of metformin and oral contraceptive combination of ethinyl estradiol and drospirenone in polycystic ovary syndrome. J Turk Ger Gynecol Assoc. 2016 Jan 12;17(1):6-9. doi: 10.5152/jtgga.201 — View Citation

Victor VM, Rovira-Llopis S, Bañuls C, Diaz-Morales N, Martinez de Marañon A, Rios-Navarro C, Alvarez A, Gomez M, Rocha M, Hernández-Mijares A. Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase. P — View Citation

Wehr E, Gruber HJ, Giuliani A, Möller R, Pieber TR, Obermayer-Pietsch B. The lipid accumulation product is associated with impaired glucose tolerance in PCOS women. J Clin Endocrinol Metab. 2011 Jun;96(6):E986-90. doi: 10.1210/jc.2011-0031. — View Citation

Wild RA, Rizzo M, Clifton S, Carmina E. Lipid levels in polycystic ovary syndrome: systematic review and meta-analysis. Fertil Steril. 2011 Mar 1;95(3):1073-9.e1-11. doi: 10.1016/j.fertnstert.2010.12.027. Review. — View Citation

Zhao X, Xu F, Qi B, Hao S, Li Y, Li Y, Zou L, Lu C, Xu G, Hou L. Serum metabolomics study of polycystic ovary syndrome based on liquid chromatography-mass spectrometry. J Proteome Res. 2014 Feb 7;13(2):1101-11. doi: 10.1021/pr401130w. — View Citation

Zhao Y, Fu L, Li R, Wang LN, Yang Y, Liu NN, Zhang CM, Wang Y, Liu P, Tu BB, Zhang X, Qiao J. Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis. BMC Med. 2012 Nov 30;10:153. doi: 10.1186/1741 — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	metabolites	Collect serum from all the subjects , through the sample pretreatment method,the metabolic features are first scanned by using Liquid Chromatography-Mass Spectrometry coupled w ith Mass Spectrometry,extracted ion-pairs were fetched to type RRLC and QTRAP(MS/MS) for multiple reaction monitoring(MRM) detection,Peak detection and alignment from the raw date use Analyst Quantitation software ,use SIMCA-P11.0 to conduct principle component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) model,use SPSS18.0 software package for statistical analysis	six months	No
Secondary	BMI	weight(kg)/ the square of height(m2)	day 1	No
Secondary	WHR		day 1	No
Secondary	FSH	use the ELISA method to detect the levels of serum FSH	day 2 to 5 in menstrual period	No
Secondary	LH	use the ELISA method to detect the levels of serum LH	day 2 to 5 in menstrual period	No
Secondary	PRL	use the ELISA method to detect the levels of serum PRL	day 2 to 5 in menstrual period	No
Secondary	T	use the ELISA method to detect the levels of serum T	day 2 to 5 in menstrual period	No
Secondary	E2	use the ELISA method to detect the levels of serum E2	day 2 to 5 in menstrual period	No
Secondary	TG	use the enzymatic method to detect the levels of serum TG	day 1	No
Secondary	CHOL	use the enzymatic method to detect the levels of serum CHOL	day 1	No
Secondary	LDL-C	use turbidity method to detect the levels of serum LDL-C	day 1	No
Secondary	HDL-C	use turbidity method to detect the levels of serum HDL-C	day 1	No
Secondary	FBG	use glucose oxidase method to detect the levels of serum FBG	day 1	No
Secondary	OGTT	The levels of blood glucose about 1, 2, 3 hours after glucose loading	day 1	No
Secondary	FINS	use radioimmunoassay to detect the levels of serum FINS	day 1	No
Secondary	insulin release test	The levels of Insulin about 1, 2, 3 hours after glucose loading	day 1	No
Secondary	HOMA index		day 1	No

External Links

•   Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome:a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome(AEPCOS)Society
•   Detection of urine metabolites in polycystic ovary syndrome by UPLC triple-TOF-MS
•   Metabonomic analysis and biomarker screening of serum for polycystic ovary syndrome patients with phlegm-dampness syndrome