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| ID | Type | Description | Link |
|---|---|---|---|
| WT209492/Z/17/Z | Other Grant/Funding Number | Wellcome Trust |
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| Name | Class |
|---|---|
| University Hospital Birmingham NHS Foundation Trust | OTHER |
| Birmingham Women's and Children's NHS Foundation Trust | OTHER |
| University Hospital of Wales | OTHER |
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Polycystic ovary syndrome (PCOS) affects 10% of all women and usually presents with irregular menstrual periods and difficulties conceiving. However, PCOS is also a lifelong metabolic disorder and affected women have an increased risk of type 2 diabetes, high blood pressure, and heart disease. Increased blood levels of male hormones, also termed androgens, are found in most PCOS patients. Androgen excess appears to impair the ability of the body to respond to the sugar-regulating hormone insulin (=insulin resistance). The investigator has found that fat tissue of PCOS patients overproduces androgens and that this can result in a build-up of toxic fat, which increases insulin resistance and could cause liver damage. In a large cohort of women registered in a GP database, the study team have found that androgen excess increases the risk of fatty liver disease. The aim is to identify those women with PCOS who are at the highest risk of developing metabolic disease, which would allow for early detection and potentially prevention of type 2 diabetes, high blood pressure, fatty liver and cardiovascular disease. The investigator will assess clinical presentation, androgen production and metabolic function in women with PCOS to use similarities and differences in these parameters for the identification of subsets (=clusters) of women who are at the highest risk of metabolic disease. The investigator will do this by using a standardised set of questions to scope PCOS-related signs and symptoms and the patient's medical history and measure body composition and blood pressure. This standardised recording of a patient's clinical presentation (=clinical phenotype) is called Phenome analysis. The investigator will collect blood and urine samples for the systematic measurement of steroid hormones including a very detailed androgen profile (=steroid metabolome analysis) and of thousands of substances produced by human metabolism (=global metabolome analysis). Phenome and metabolome data will then undergo integrated computational analysis for the detection of clusters predictive of metabolic risk.
The investigator propose an innovative approach to solving the clinical problem at hand, the lack of identified measurable parameters one can use to predict the risk of future metabolic disease in women diagnosed with PCOS.The chosen approach is the standardised collection of phenome and metabolome data and their unbiased integration by machine learning analysis. Utilising the detailed results of the clinical phenome and metabolome analysis in the DAISy-PCOS Phenome Study cohort, The study will aim to identify distinct subsets (=clusters) of PCOS patients that share similar characteristics. This approach has previously been used by the team to successfully identify distinct steroid markers that can serve as a "malignant steroid fingerprint" in urine to distinguish benign from malignant tumours in patients with incidentally discovered adrenal masses. Similarly, The investigator have used unbiased analysis of steroid metabolome data to reveal that patients with aldosterone excess also overproduce glucocorticoids and that the latter explains the majority of metabolic disease risk observed in affected patients.
In the integrated analysis of the DAISy-PCOS phenome and metabolome data, The investigator will apply a variety of methods in the context of connectivity or centroid-based clustering and density estimation. Supervised relevance learning will give insight into markers, e.g. steroids, that are most decisive for the determination of cluster memberships. In addition, The investigator will use state-of-the-art visualisation and machine learning techniques based on adaptive similarity measures.the investigator will use integrative approaches, addressing the heterogeneous data from different sources as a whole, whilst considering data-driven adaptation of generative models for the underlying biological processes. The investigator will employ these approaches to characterise central phenotype clusters affecting large numbers of patients as the basis of personalised management including outcome prediction.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Women with polycystic ovary syndrome | Other | Prospective cohort study in women with polycystic ovary syndrome to identify the risk of developing metabolic disease |
| Measure | Description | Time Frame |
|---|---|---|
| Metabolic risk | Metabolic-risk prediction model would be made from a machine learning algorithm where the study team would be able to enter phenome and metabolome data of patient with a new diagnosis of PCOS. With this model, the study team would be able to stratify the women with PCOS into their risk of metabolic disease hence personalise the management of the condition | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Dissect the severity and pattern of androgen excess in development of metabolic disease | The study team would assess how pattern of androgen excess in each phenotype relates to their risk of metabolic disease | 5 years |
| Eligibility for other PCOS-related studies |
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Inclusion Criteria:
Exclusion Criteria:
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Women with a new diagnosis of Polycystic ovary syndrome aged 18-70 who are treatment naive
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Eka Melson | Contact | +447852146611 | e.melson@bham.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Wiebke Arlt | University of Birmingham | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wellcome Trust Clinical Research Facility | Recruiting | Birmingham | West Midlands | B15 2TT | United Kingdom |
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| ID | Term |
|---|---|
| D011085 | Polycystic Ovary Syndrome |
| ID | Term |
|---|---|
| D010048 | Ovarian Cysts |
| D003560 | Cysts |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 |
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| University Hospitals Coventry and Warwickshire NHS Trust |
| OTHER |
| Royal Infirmary of Edinburgh | OTHER |
| Royal College of Surgeons, Ireland | OTHER |
| Imperial College Healthcare NHS Trust | OTHER |
| Hull University Teaching Hospitals NHS Trust | OTHER_GOV |
| King's College Hospital NHS Trust | OTHER |
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DNA will be stored in a Human tissue act approved site and ethics for a potential future analysis
Participants will be screened for their eligibility to enroll in other PCOS-related research studies |
| 3 years |
| Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |