Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT04912648 |
Other study ID # |
20/49 |
Secondary ID |
|
Status |
Recruiting |
Phase |
|
First received |
|
Last updated |
|
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 |
Health authority |
|
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.