FEmale Metabolic Risk and Androgens: an Irish Longitudinal (FEMAIL) Study

Metabolic Disease Clinical Trial

— FEMAIL  

Official title:

FEmale Metabolic Risk and Androgens: an Irish Longitudinal (FEMAIL) Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04912648
• Other study ID #: 20/49
• Status: Recruiting
• Start date: April 1, 2021
• Est. completion date: August 31, 2031

Study information

• Verified date: May 2024
• Source: Royal College of Surgeons, Ireland
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Androgen excess is the cardinal biochemical feature of polycystic ovary syndrome (PCOS), a lifelong metabolic disorder affecting 10% of women. Serum testosterone correlates with insulin resistance in women, however, there is an urgent need to improve our understanding of the association between androgens and the risk of type 2 diabetes. Recently, a new subclass of androgenic steroids known as 11-oxygenated androgens has been identified. Utilising highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques, our group has recently demonstrated that 11-oxygenated steroids are the predominant androgens in both health controls and women with PCOS, and that these correlate closely with markers of insulin resistance. The bioactive 11-oxygenated androgen 11-ketotestosterone (11KT) binds and activates the androgen receptor with equal affinity to testosterone, yet nothing is known about its impact on metabolism or glucose homeostasis. Intriguingly, unlike testosterone, 11-oxygenated androgens do not decline with age in women, and, therefore, may mediate an increased risk of T2DM in women across their life course. Therefore, this previously ignored androgen class is likely of major importance in female metabolic health, and may represent a novel metabolic risk factor and biomarker. However, 11-oxygenated androgens are not currently measured in routine clinical practice. To date, no population-based or human in vivo physiology studies have examined the association between 11-oxygenated androgens, glucose metabolism and diabetes risk in women, despite the high prevalence of PCOS in the female population. There is emerging evidence, even in women without a confirmed history of PCOS, that the levels of androgens over time correlate with their likelihood of developing metabolic and cardiovascular disease. This has not been studied to date in a prospective manner in healthy women in the background population using long term follow up data.

Description:

Clinical questionnaire and baseline anthropometry: Study investigators will complete a standardised case record form, with information obtained on relevant medical history, medications and anthropometric assessment (height, weight, body mass index, blood pressure, weight circumference). Body composition will be assessed using a portable bioimpedance machine (Tanita MC-780MA-S Portable). We will also obtain information on education level and household income. Participants will complete a standardised QOL questionnaire. Serum, urine and saliva sampling: Fasting bloods will be drawn for assessment of metabolic phenotype including glucose, insulin, lipid profile, full blood count, renal and liver biochemistry and HbA1C. Serum samples will also be obtained for measured of the steroid and non-targeted metabolome. Urine and saliva samples will be obtained for assessment of steroid metabolomics. Targeted steroid metabolome profiling: Serum, urinary and salivary multi-steroid profiling including classic and 11-oxygenated androgens will be performed using highly sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS). Furthermore, we will analyse the 24-h urine steroid metabolome, allowing for determination of 24-h net androgen output from classic and 11-oxygenated pathways (26). Analysis will be carried out by LC-MS/MS multi-steroid profiling. Multi-steroid profiling approaches have been developed and optimised at the University of Birmingham Steroid Metabolome Analysis Core (SMAC), where samples will be measured under the supervision of Professor Wiebke Arlt. Non-targeted serum metabolomics: The global non-targeted serum metabolome will be profiled at the Phenome Centre Birmingham under the supervision of Professor Warwick Dunn (co-applicant). Samples will be analysed applying Ultra Performance Liquid Chromatography (Ultimate3000RS; Thermo Scientific, Hemel Hempstead, UK) interfaced to an electrospray mass spectrometry (Q Exactive, Thermo Scientific, Hemel Hempstead, UK). Muscle biopsy: Under local anaesthetic and without using scalpel incision, muscle biopsies will be obtained from the vastus lateralis muscle of the leg in each participant. These will be performed using a Bard biopsy needle gun, with suction applied to increase tissue yield. Recruitment: Patients will be recruited via local advertising in Beaumont Hospital and RCSI Medical School.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: August 31, 2031
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 years or above
• Ability to provide informed consent

Exclusion Criteria:

• Pregnancy or breastfeeding at the time of planned recruitment
• History of significant renal (eGFR<30) or hepatic impairment (AST or ALT >two-fold above ULN; pre-existing bilirubinaemia >1.2 ULN)
• The investigators will retain the right not to recruit potential participants with severe health disorders which may impact on their ability to participate in the study; these may include, but are not limited to, metastatic cancer, severe cardio-respiratory disease or other life-limiting health disorders
• Participants who have participated in another research study involving an investigational medicinal product in the 12 weeks preceding the planned recruitment
• Glucocorticoid use via any route within the last six months
• Current intake of drugs known to impact upon steroid or metabolic function or intake of such drugs during the six months preceding the planned recruitment
• Use of combined oral hormonal contraception in the three months preceding the planned recruitment

Related Conditions & MeSH terms

• Hyperandrogenism
• Metabolic Disease
• Metabolic Diseases

Intervention

Other:
• Longitudinal follow up
Repeat follow up at 3,5 and 10 years

Locations

Country	Name	City	State
Ireland	Royal College of Surgeons in Ireland	Dublin

Sponsors (1)

Lead Sponsor	Collaborator
Royal College of Surgeons, Ireland

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation of sex hormone profiles and the metabolome of women across the lifespan with risk of metabolic dysfunction, cardiovascular disease and quality of life.		3 years
Secondary	Development of risk prediction models for development of diabetes in women		5 years
Secondary	Establishment of the longitudinal FEMAIL study database		5 years