HyperandrogenismFEMAILNCT04912648
FEmale Metabolic Risk and Androgens: an Irish Longitudinal (FEMAIL) Study
An observational study of Hyperandrogenism and Metabolic Disease, run by Royal College of Surgeons, Ireland at 1 site in Ireland.
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… Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Hyperandrogenism, Metabolic Disease, Sex Hormones Adverse Reaction
- What is being tested?
- Longitudinal follow up
- How many people
- 500 participants
- Where
- 1 siteIreland
- Study dates
- 1 Apr 2021to 31 Aug 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Women meeting the above inclusion criteria without exclusion criteria
Who may be able to join
- Age 18 years or above
- Ability to provide informed consent
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Ireland1 site, 1 recruiting
- Recruiting
Royal College of Surgeons in Ireland
Dublin, D9
Michael W O'Reilly, FRCPI PhD, 0035318093894, michaelworeilly@rcsi.com
Michael W O'Reilly, FRCPI PhD
About this study
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.
Read the detailed 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.
- Being tested
- Longitudinal follow up
- Medical subject headings
- Hyperandrogenism, Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Longitudinal follow upOther
Repeat follow up at 3,5 and 10 years
| Study group | Role | What they receive |
|---|---|---|
| Women age 18 years and older | * baseline anthropometry
* bloods for metabolic phenotype; targeted and nontargeted Metabolomics
* saliva and urine for steroid Metabolomics
* bioimpedance
* muscle biopsy for transcriptomics Receives: Other: Longitudinal follow up |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation of sex hormone profiles and the metabolome of women across the lifespan with risk of metabolic dysfunction, cardiovascular disease and quality of life.
Measured: 3 years
Secondary outcomes (2)
Development of risk prediction models for development of diabetes in women
Measured: 5 years
Establishment of the longitudinal FEMAIL study database
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2021
- Study start1 Apr 2021
- Primary completion1 Sep 2025 (estimated)
- Study completion31 Aug 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyperandrogenismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal College of Surgeons, Ireland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04912648
- Sponsor's protocol ID
- 20/49
- Acronym
- FEMAIL
- Status last verified
- May 2024
- First submitted
- 28 May 2021
- Last updated
- 2 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Anonymised data may be made available after consideration of individual access requests, in line with data protection laws and participant consent
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FEmale Metabolic Risk and Androgens: an Irish Longitudinal (FEMAIL) Study
- ClinicalTrials.gov ID
- NCT04912648
- Acronym / sponsor ID
- FEMAIL / 20/49
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Royal College of Surgeons, IrelandUniversity, hospital or other
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 1 Sep 2025 (estimated)
- Study completion
- 31 Aug 2031 (estimated)
- First posted
- 3 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Women age 18 years and older | – | Other: Longitudinal follow up* baseline anthropometry * bloods for metabolic phenotype; targeted and nontargeted Metabolomics * saliva and urine for steroid Metabolomics * bioimpedance * muscle biopsy for transcriptomics |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Women meeting the above inclusion criteria without exclusion criteria
Key inclusion criteria (2 listed)
- Age 18 years or above
- Ability to provide informed consent
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Longitudinal follow upRepeat follow up at 3,5 and 10 years | Other | Women age 18 years and older |
Primary outcome
Correlation of sex hormone profiles and the metabolome of women across the lifespan with risk of metabolic dysfunction, cardiovascular disease and quality of life.
Time frame: 3 years
2 secondary outcomes
Development of risk prediction models for development of diabetes in women
Time frame: 5 years
Establishment of the longitudinal FEMAIL study database
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2024.
- Individual participant dataSharing planned: Undecided. Anonymised data may be made available after consideration of individual access requests, in line with data protection laws and participant consent
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hyperandrogenism and Metabolic Disease, run by Royal College of Surgeons, Ireland at 1 site in Ireland.
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 2 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 2 May 2024. 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 Ireland. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation of sex hormone profiles and the metabolome of women across the lifespan with risk of metabolic dysfunction, cardiovascular disease and quality of life. (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 May 2024.