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Polycystic Ovary SyndromePhase 3NCT03843736

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

A Phase 3 study testing Lifestyle intervention, Probiotic Agent and Oral contraceptive in people with Polycystic Ovary Syndrome, run by Peking Union Medical College Hospital at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for
Polycystic Ovary Syndrome
What is being tested?
Lifestyle intervention, Probiotic Agent and Oral contraceptive
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
1 siteChina
Study dates
21 Feb 2019to 31 Dec 2020
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 45 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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;
  • 2 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.

Who cannot join

  • pregnancy;
  • menopause;
  • adrenal abnormalities;
  • thyroid dysfunction;
  • taking antibiotics for the past 3 months;
  • is taking oral contraceptive treatment;
Show all 9Show fewer
  • basic diseases of the gastrointestinal tract (ulcerative colitis, Crohn's disease, inflammatory bowel disease, etc.);
  • history of smoking;
  • BMI<18kg/m2.

Trial locations and contacts

1 site in 1 country.

Rong Chen, Ph. D. contact

(86-10)-69155012

chenrongpumch@163.com

Xu Zhang, master contact

zhangxu_5050@163.com

China1 site, 1 recruiting

  • Peking Union Medical College Hospital

    Beijing

    Rong Chen, Ph. D, (86-10)-69155012, chenrongpumch@163.com

    Xu Zhang, Master, zhangxu_5050@163.com

    Recruiting

Other trials in China

About this study

Official title: The Role of Dysbiosis of Gut Microbiota in the Pathogenesis of Polycystic Ovary Syndrome.

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.

Read the detailed description
  1. Data quality assurance: ① all inspections and measurements will be performed by either the hospital or the sequencing company personnel according to standard operating procedures (SOPs), except for saliva and stool samples, which will be self-collected by patients. For sample collection, we will provide text descriptions of the SOPs as well as video instruction. Designated staff will be assigned for support and can be contacted if participants have any queries concerning sample collection; ② a case report form (CRF) will be prepared according to the current SOPs, and detailed instructions will be provided to ensure consistency in data collection. At the same time, each CRF will be properly stored at least 5 years for verification and backtracking; ③ all experimental data will be logged into the database to ensure information accuracy based on the existing data; ④ we will keep the contact information of each participant, remind them of precautions during participation, and conduct regular follow-ups.
  2. Sample size determination: The number of participants is based on comparable sample sizes in the literature. In this trial, there will be 50 healthy individuals (control group) and 150 PCOS (polycystic ovary syndrome) patients. The 150 PCOS patients will be randomly assigned to three intervention groups. This sample size accounts for a plausible insufficiency of data caused by patient dropouts and withdrawals before the study is completed. The participation cycle is of approximately four months, followed by a 2-year follow-up.
  3. Metagenomic sequencing technology Metagenomic sequencing is the main technique used in this study. Metagenomics, also known as economics, was first proposed by Handelman and studies the molecular composition of microbial populations, their interactions, and gene functions. In medicine, metagenomics compares the structural and functional changes of human microbial communities under normal and disease states. It can analyze the diversity and the functional differences of microbial communities from healthy individuals and from patients with diseases, thus determine how diseases relate to changes in the microbial communities and in their respective metabolic networks. Therefore, metagenomics provides theoretical evidence for disease prevention, detection, and treatment. At present, the internationally renowned Human Microbiome Project (HMP, http://www.hmpdacc.org/) and the Metagenomics of the Human Intestinal Tract (MetaHIT) are typical applications of metagenomics in medicine. [Metagenomic species, genes, and functional annotation] ① Data quality control: the sequenced raw data will contain a certain amount of low-quality data, so quality control must be performed. Only high-quality data can correctly reflect the actual occurrence of microorganisms in the sample. ② Metagenome assembly: based on Clean Data, individual samples will be assembled separately at first, then reads that do not participate in the assembling above will be combined and mixed for assembly. This will increase the sequencing depth of low-abundance species in each sample and provide more sequencing information for each species. ③ Gene prediction: MetaGeneMark will be used for gene prediction based on single samples and mixed-assembled scaftigs. The redundancy of all predicted genes will be reduced to obtain a Uniq gene set. Then, the Clean Data of each sample will be compared to the gene set and the abundance of the gene set will be determined for each sample. ④ Species annotation: Clean Data will be used for quality control. It will be compared with an annotated according to reference genome databases of bacteria, archaea, viruses, and fungi from NCBI. A species abundance table will be obtained for each sample at different classification levels. ⑤ Functional annotation: functional annotation and abundance statistics will be based on the Uniq gene set and the KEGG database.
Being tested
Lifestyle intervention, Probiotic Agent, Oral contraceptive
Keywords
Polycystic Ovary Syndrome, Metagenomics, Metabonomics
Medical subject headings
Polycystic Ovary Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lifestyle interventionBehavioural

    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.

  • Probiotic AgentDrug

    Also called Tangwen Tai

    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.

  • Oral contraceptiveDrug

    Also called Drospirenone and Ethinylestradiol Tablets, Yousi Yue

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

Study groups in NCT03843736
Study groupRoleWhat they receive
Health control groupNo interventionParticipants are healthy women and there are no interventions.
Lifestyle interventions groupExperimentalParticipants are PCOS patients and only will be given lifestyle interventions.
Receives: Drug: Probiotic Agent; Drug: Oral contraceptive
Probiotic Agent groupExperimentalParticipants are PCOS patients and will be given lifestyle interventions + Probiotic Agent interventions.
Receives: Behavioral: Lifestyle intervention; Drug: Oral contraceptive
Oral contraceptive groupExperimentalParticipants are PCOS patients and will be given lifestyle intervention + Oral contraceptive interventions.
Receives: Behavioral: Lifestyle intervention; Drug: Probiotic Agent

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Through study completion, an average of 12 weeks

  2. 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.

    Measured: Through study completion, an average of 12 weeks

  3. 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.

    Measured: Through study completion, an average of 12 weeks

  4. 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.

    Measured: Through study completion, an average of 12 weeks

Secondary outcomes (2)

  1. Insulin resistance

    Use glucose tolerance and insulin test (75gOGTT+insulin) to assess whether the patient has insulin resistance, as well as the level of insulin resistance.

    Measured: Through study completion, an average of 12 weeks

  2. Androgen level

    Six-sex-hormone tests, one of the clinical examination items, will be performed to measure androgen levels in the subjects.

    Measured: Through study completion, an average of 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Feb 2019
  2. Study start21 Feb 2019
  3. Primary completion30 Jun 2020 (estimated)
  4. Study completion31 Dec 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03843736
Sponsor's protocol ID
JS-1691
Other IDs
81871141
Status last verified
Oct 2019
First submitted
11 Feb 2019
Last updated
10 Oct 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: According to national laws and regulations, human genetic resources may not be provided abroad.

Publications

  • 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.

    PubMed 21609197

  • 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.

    PubMed 22543078

  • 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.

    PubMed 28293234

  • 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.

    PubMed 27093642

  • 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.

    PubMed 29370410

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lifestyle intervention, Probiotic Agent and Oral contraceptive in people with Polycystic Ovary Syndrome, run by Peking Union Medical College Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 10 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Rong Chen, Ph. D. ((86-10)-69155012, chenrongpumch@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Diversity analysis of genes and species (time frame: Through study completion, an average of 12 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03843736, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2019.

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