The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of PCOS.

NCT03843736 | Unknown Phase 3

• 2 other identifiers: JS-169181871141
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Polycystic ovary syndrome (PCOS) has a significant impact on women's health, but its pathogenesis is not yet clear. Dysbiosis of gut microbiota may play a role in the pathological change of PCOS. Most of the current researches are still limited to the use of amplicon sequencing to compare the basic taxonomic differences of gut microbiota between PCOS patients and normal controls. Overall analysis of microbiome species, genes, function, metabolism, and immunity in PCOS is still lacked. In this research, we would perform metagenomic sequencing to find the characteristics of gut microbiota of PCOS and to explore their correlations with metabolic, immune, and clinical symptoms. Finally, different interventions (lifestyle interventions, lifestyle interventions + oral probiotic, lifestyle interventions+ compound oral contraceptives) would be used to explore the change of gut microbiome in PCOS patients. This research will not only help the understanding of the pathophysiology of PCOS, but also provide a reference for the selection of clinical treatment options.

Conditions

Polycystic Ovary Syndrome

Keywords

Polycystic Ovary Syndrome; Metagenomics; Metabonomics

Outcome Measures

Primary Outcomes (4)

• Diversity analysis of genes and species

  Based on the gene and species composition of each sample, the Chao1 and Shannon indexes, as well as the observed OTUs (operational taxonomic units), will be calculated in order to identify the differences in gene and species diversity for each group.

  Through study completion, an average of 12 weeks

• Analysis of differences in intestinal microbiota between PCOS patients and the control group

  The Spearman correlation coefficient between genes will be calculated, and genes with strong correlation will be grouped into one cluster, as a CAG. The abundance of CAGs in each sample will be determined Furthermore, the significantly enriched species in the control and PCOS groups will be enumerated for network display.

  Through study completion, an average of 12 weeks

• Analysis of functional differences in the intestinal microbiota of PCOS patients in comparison to the control group

  The LEfSe discriminant analysis will be used to screen for significant differences between groups. The dimensionality reduction will be implemented by LDA, and the impact of function difference will be evaluated to obtain the LDA score and identify significantly different functions between groups.

  Through study completion, an average of 12 weeks

• Correlation analysis between biomarkers and clinical indicators

  For the obtained species, genes, or functions with significant difference, the correlation between them and clinical indicators will be calculated, and key biomarkers with significant and strong correlation will be identified.

  Through study completion, an average of 12 weeks

Secondary Outcomes (2)

• Insulin resistance

  Through study completion, an average of 12 weeks

• Androgen level

  Through study completion, an average of 12 weeks

Study Arms (4)

Health control group

NO INTERVENTION

Participants are healthy women and there are no interventions.

Lifestyle interventions group

EXPERIMENTAL

Participants are PCOS patients and only will be given lifestyle interventions.

Drug: Probiotic Agent; Drug: Oral contraceptive

Probiotic Agent group

EXPERIMENTAL

Participants are PCOS patients and will be given lifestyle interventions + Probiotic Agent interventions.

Behavioral: Lifestyle intervention; Drug: Oral contraceptive

Oral contraceptive group

EXPERIMENTAL

Participants are PCOS patients and will be given lifestyle intervention + Oral contraceptive interventions.

Behavioral: Lifestyle intervention; Drug: Probiotic Agent

Interventions

Lifestyle intervention BEHAVIORAL

1. Balance the diet; 2. Limit high-calorie and high-fat food intake, reduce eating out, and establish regular eating habits; 3. Monitor body weight, avoid sedentary, get more sun and regular activities; 4. Mental health regulation.

Oral contraceptive group; Probiotic Agent group

Probiotic Agent DRUG

Patients have to take a probiotic powder (product name: Tangwen Tai, lactobacillus plantarum LP45 + Lactobacillus acidophilus La28 + Bifidobacterium lactobacillus BAL531) twice a day for three months.

Also known as: Tangwen Tai

Lifestyle interventions group; Oral contraceptive group

Oral contraceptive DRUG

The patient needs to take drospirenone ethinyl estradiol tablets (trade name: Yousi Yue) 1 tablet daily for 3 months.

Also known as: Drospirenone and Ethinylestradiol Tablets, Yousi Yue

Lifestyle interventions group; Probiotic Agent group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Polycystic ovary syndrome (PCOS) is a syndrome of endocrine disorders characterized by sparse ovulation or anovulation, high androgen or insulin resistance, and polycystic ovary. PCOS is a woman-specific disease, so participants must be women.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Conforms to the 2003 Rotterdam classic PCOS diagnostic criteria.
• sparse ovulation or anovulation;
• clinical manifestations of high androgen and/or hyperandrogenism;
• ovarian polycystic changes: ultrasound suggests one or both sides of the ovary with a diameter of 2-9 mm follicles ≥ 12, and / or ovarian volume ≥ 10 ml;
• out of 3 items, and exclude other high androgen causes, such as congenital adrenal hyperplasia, Cushing's syndrome, and androgen-secreting tumors;
• Age: 18-45 years old.

You may not qualify if:

• pregnancy;
• menopause;
• adrenal abnormalities;
• thyroid dysfunction;
• taking antibiotics for the past 3 months;
• is taking oral contraceptive treatment;
• basic diseases of the gastrointestinal tract (ulcerative colitis, Crohn's disease, inflammatory bowel disease, etc.);
• history of smoking;
• BMI\<18kg/m2.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Peking Union Medical College: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, China

RECRUITING

Related Publications (5)

• Alvarez-Blasco F, Luque-Ramirez M, Escobar-Morreale HF. Diet composition and physical activity in overweight and obese premenopausal women with or without polycystic ovary syndrome. Gynecol Endocrinol. 2011 Dec;27(12):978-81. doi: 10.3109/09513590.2011.579658. Epub 2011 May 24.

  PMID: 21609197 BACKGROUND

• Tremellen K, Pearce K. Dysbiosis of Gut Microbiota (DOGMA)--a novel theory for the development of Polycystic Ovarian Syndrome. Med Hypotheses. 2012 Jul;79(1):104-12. doi: 10.1016/j.mehy.2012.04.016. Epub 2012 Apr 27.

  PMID: 22543078 BACKGROUND

• Liu R, Zhang C, Shi Y, Zhang F, Li L, Wang X, Ling Y, Fu H, Dong W, Shen J, Reeves A, Greenberg AS, Zhao L, Peng Y, Ding X. Dysbiosis of Gut Microbiota Associated with Clinical Parameters in Polycystic Ovary Syndrome. Front Microbiol. 2017 Feb 28;8:324. doi: 10.3389/fmicb.2017.00324. eCollection 2017.

  PMID: 28293234 BACKGROUND

• Guo Y, Qi Y, Yang X, Zhao L, Wen S, Liu Y, Tang L. Association between Polycystic Ovary Syndrome and Gut Microbiota. PLoS One. 2016 Apr 19;11(4):e0153196. doi: 10.1371/journal.pone.0153196. eCollection 2016.

  PMID: 27093642 RESULT

• Torres PJ, Siakowska M, Banaszewska B, Pawelczyk L, Duleba AJ, Kelley ST, Thackray VG. Gut Microbial Diversity in Women With Polycystic Ovary Syndrome Correlates With Hyperandrogenism. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1502-1511. doi: 10.1210/jc.2017-02153.

  PMID: 29370410 RESULT

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

Contraceptives, Oral; drospirenone; Ethinyl Estradiol

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Rong Chen, Ph. D.

  Beijing Union Medical College Hospital

  STUDY DIRECTOR

Central Study Contacts

Rong Chen, Ph. D.

CONTACT

(86-10)-69155012; chenrongpumch@163.com

Xu Zhang, master

CONTACT

zhangxu_5050@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will collect 50 healthy participants and 150 PCOS participants. At the same time, 150 patients with PCOS will be randomly divided into the lifestyle intervention group, lifestyle interventions + Probiotic Agent group, lifestyle intervention + oral contraceptive group by random number table method.

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: February 18, 2019
• Study Start: February 21, 2019
• Primary Completion: June 30, 2020
• Study Completion: December 31, 2020
• Last Updated: October 10, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)