Polycystic Ovary Syndrome11OXO-PCOSNCT05246865
Impact of 11-oxygenated Androgens on Metabolic Dysfunction of Women With Polycystic Ovary Syndrome
A study testing oral androgen challenge with dehydroepiandrosterone (DHEA) in people with Polycystic Ovary Syndrome, run by University of Birmingham at 1 site in United Kingdom.
Trial summary
Polycystic ovary syndrome (PCOS) affects 10% of all women and usually presents with irregular menstrual periods and difficulties conceiving. It is also a lifelong metabolic disorder and affected women have an increased risk of type 2 diabetes, high blood pressure, and heart disease. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Polycystic Ovary Syndrome
- What is being tested?
- oral androgen challenge with dehydroepiandrosterone (DHEA)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Oct 2021to 30 May 2025
- Phase
- Interventional
- 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 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- BMI between 30-40 kg/m2
- Age range 18-40 years
- Ability to provide informed consent
- For women participating in the PCOS group, the diagnosis of PCOS will be established during their recruitment to DAISy-PCOS study on the basis of the Rotterdam Consensus Criteria for the Diagnosis of PCOS, as recommended by the current international PCOS guidelines (at least 2 out of 3 criteria):
- Androgen excess (clinical and/or biochemical evidence)
- Chronic oligo-/anovulation (clinical and/or biochemical evidence)
- Polycystic appearance of the ovaries on ultrasound (according to the most recent guidelines (10), taking into account the higher resolution capacity of modern ultrasound, the presence of ovarian PCOS morphology is defined as follows: 20 or more follicles of 2-9mm in diameter and/or an increased ovarian volume >10 millilitre [without a cyst or dominant follicle] in either ovary) In addition, we will perform clinical and/or biochemical exclusion, as appropriate, of other conditions that could explain the above manifestation (e.g. congenital adrenal hyperplasia, Cushing's syndrome, Prolactinoma, adrenal and gonadal tumours)
Who cannot join
- Pregnancy or breastfeeding at the time of planned recruitment
- History of significant renal (eGFR<30) or hepatic impairment (aspartate aminotransferase or alanine transaminase >two-fold above ULN; pre-existing bilirubinaemia >1.2 ULN)
- Any other significant disease or disorder that, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
- 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 synthesis or metabolism or on metabolic function or intake of such drugs during the six months preceding the planned recruitment
Show all 19Show fewer
- Use of oral or transdermal hormonal contraception in the three months preceding the planned recruitment
- Use of contraceptive implants in the twelve months preceding the planned recruitment
- Allergy or intolerance to any of the ingredients in the high fat meal, or any of the ingredients in the dehydroepiandrosterone and 11-ketoandrostenedione preparations.
- Diabetes or impaired glucose metabolism
- Part B Inclusion criteria
- Women undergoing elective, abdominal, non-cancer surgery
- Age range 18-70 years
- Ability to provide informed consent
- Pregnancy or breastfeeding at the time of planned recruitment
- Glucocorticoid use via any route within the last six months
- Current intake of drugs known to impact upon steroid synthesis or metabolism or on metabolic function or intake of such drugs during the six months preceding the planned recruitment
- Type 1 diabetes
- Medical treatment of type 2 diabetes
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Institute of Metabolism and Systems Research
Birmingham, West Midlands, B15 2TT
Wiebke Arlt, MD DSc, +447792016879, w.arlt@bham.ac.uk
Punith Kempegowda, MSc MD MRCP, +447721930777, p.kempegowda@bham.ac.uk
About this study
Official title: The Role of 11-oxygenated Androgens in Androgen Excess and Metabolic Dysfunction of Women With Polycystic Ovary Syndrome
Polycystic ovary syndrome (PCOS) affects 10% of all women and usually presents with irregular menstrual periods and difficulties conceiving. It 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 (also termed 'insulin resistance'). Androgens circulating in the blood in women with PCOS are comprised of classic androgens (for example testosterone), and the less-characterised 11-oxygenated androgen subclass that arises from the adrenal glands. The investigators have recently demonstrated that 11-oxygenated androgens make up the majority of circulating androgens in women with PCOS.
In preliminary studies using minimally invasive adipose tissue sampling, the investigators have found that the fat tissue of women with PCOS overproduces classic androgens. This can lead directly to disturbances in the ability of fat cells to store fat effectively (lipotoxicity), resulting in insulin resistance and the consequent risk of liver damage. However, there are no published studies on in vivo androgen concentrations in the adipose tissue of women with PCOS. Furthermore, the scientific community do not have any information on whether adipose concentrations of 11-oxygenated androgens are also increased in women with PCOS.
Research Questions The investigators aim to examine the metabolism of classic and 11-oxygenated androgens in detail in both circulations and in the adipose tissue of women with PCOS. The investigators will examine how precursor variants of both 11-oxygenated and classic androgens, which are converted by the body into active hormones, are broken down (metabolised) within the adipose tissue of women with PCOS. The investigators will also investigate if the 11-oxygenated androgens have a differential impact on metabolic function as compared to classic androgens. This will give important insights into the adipose tissue metabolome in women with PCOS, and how locally generated androgens impact on adipose tissue function and metabolic risk.
Read the detailed description
In part A of the study, women with PCOS and obesity, identified from the previously established DAISy-PCOS cohort, and age- and BMI-matched healthy volunteers identified by advertisements, will be invited for a screening visit (Visit 1) at the National Institute of Health Research-Wellcome Trust Clinical Research Facility at the Queen Elizabeth Hospital Birmingham. Once eligibility (described in detail in Section 7.1) has been confirmed, a written informed consent will be obtained, and the volunteers will be invited to three further metabolic assessment visits after an overnight fast.
While Visits 2 and 3 (Study days 1 and 2, respectively) will be for the assessment of responses to an androgen-precursor challenge, Visit 4 (Study day 3) will run in the same format as the previous two Study days except no androgen will be administered. During each visit, study participants will undergo abdominal adipose tissue vein cannulation, whereby a catheter will be inserted (under ultrasound guidance and with local anaesthetic) into one of the veins of the abdominal fat tissue. Ultrasound Doppler and ethanol dilution by microdialysis will be employed to assess adipose tissue blood flow. A further catheter will be inserted into a vein on the back of the hand which will be placed a hot air box in order to obtain arterialised blood. Finally, a catheter will be inserted into an antecubital vein for the purposes of stable isotope infusion. Blood samples from the hand vein and from the abdominal adipose tissue vein will be taken in tandem every 30 minutes for measurement of various metabolites, androgens, and non-targeted metabolome studies. Salivary samples will be collected every 30 minutes in the first hour and hourly thereafter until the end of the study. Urine will be collected throughout the Study Visit. At time point 240 min, a standardised high-fat meal containing palmitate labelled with a stable isotope will be given to the participant, and measurements will continue, to assess how their metabolism responds to the meal. Furthermore, fat tissue biopsies will be taken from the subcutaneous abdominal adipose tissue at the end of each study day. These fat biopsies will undergo RNA extraction for transcriptional profiling by RNA-sequencing and will be used for tissue incubation to determine their androgen-generating and metabolic capacity.
On Visits 2 and 3, participants will be administered either the classic androgen pathway precursor dehydroepiandrosterone or the 11-oxygenated androgen pathway precursor 11-ketoandrostenedione at time point 0 min. No androgen precursors will be administered during Visit 4. Otherwise, Visits 2-4 will be identical in their flow.
In part B of the study, paired subcutaneous and omental adipose tissue samples (up to 5 g), as well as a blood sample, are collected from female volunteers undergoing elective abdominal surgery. These tissue samples alongside the subcutaneous tissue obtained from the in vivo study (part A) will be used for ex vivo incubations with androgen precursors to study androgen activation and its metabolic impact. Additionally, the effect of Aldo-Keto Reductase Family 1 Member C3 inhibition on androgen activation will be assessed in ex vivo incubations. After the incubation, the culture medium and/or the tissue will be used for metabolome analysis (non-targeted global metabolome and steroid metabolome profiling) and transcriptome analysis. The blood sample will be used for serum multi-steroid profiling.
- Conditions
- Polycystic Ovary Syndrome
- Being tested
- oral androgen challenge with dehydroepiandrosterone (DHEA)
- 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.
oral androgen challenge with dehydroepiandrosterone (DHEA)Drug
Also called oral androgen challenge with 11-ketoandrostenedione
The oral androgen challenge is a safe and well-validated means of studying the androgen generation profiles of different study groups.
| Study group | Role | What they receive |
|---|---|---|
| Women with PCOS | Experimental | Women with polycystic ovary syndrome Receives: Drug: oral androgen challenge with dehydroepiandrosterone (DHEA) |
| Age and BMI-matched healthy volunteers | Experimental | Otherwise healthy women without PCOS but matching in age and body mass index to the above group Receives: Drug: oral androgen challenge with dehydroepiandrosterone (DHEA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline height
During Visit 1, the research team will measure height in centimetres
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline weight
During Visit 1, the research team will measure weight in kilogram
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline body mass index (BMI)
During Visit 1, weight and height will be combined to report BMI in kg/m^2
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline waist circumference
During Visit 1, the research team will measure Waist circumference to nearest centimetre
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline blood pressure
During Visit 1, the research team will measure both systolic and diastolic Blood pressure in mmHg after 10 minutes in sitting position
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline urea & electrolytes
During Visit 1, the research team will collect blood to measure urea \& electrolytes in mmol/L
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline liver function test
During Visit 1, the research team will collect blood to measure liver function tests in mmol/L
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline haemoglobin
During Visit 1, the research team will collect blood to measure haemoglobin in grams per litre
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline white cell and platelet count
During Visit 1, the research team will collect blood to measure White cell and platelets in number of cells per ml
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline lipid profile
During Visit 1, the research team will collect blood to measure lipid profile in mmol/L
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline glucose
During Visit 1, the research team will collect blood to measure glucose in mmol/L
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline glycated haemoglobin
During Visit 1, the research team will collect blood to measure glycated haemoglobin (HbA1c) in mmol/mol
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline thyroid function test
During Visit 1, the research team will collect blood to measure thyroid function test in mIU/L
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline Dehydroepiandrosterone (DHEAS)
During Visit 1, the research team will collect blood to measure DHEAS in µmol/L
Measured: 3 years
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline androstenedione
During Visit 1, the research team will collect blood to measure androstenedione in µmol/L
Measured: 3 years
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline testosterone
During Visit 1, the research team will collect blood to measure testosterone in nmol/L
Measured: 3 years
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline sex hormone binding globulin
During Visit 1, the research team will collect blood to measure sex hormone binding globulin in nmol/L
Measured: 3 years
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline 17-hydroxyprogesterone
During Visit 1, the research team will collect blood to measure 17-hydroxyprogesterone in nmol/L
Measured: 3 years
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline prolactin
During Visit 1, the research team will collect blood to measure prolactin in mIU/L
Measured: 3 years
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline Follicle-stimulating hormone
During Visit 1, the research team will collect blood to measure Follicle-stimulating hormone in IU/L
Measured: 3 years
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline luteinizing hormone
During Visit 1, the research team will collect blood to measure luteinizing hormone in IU/L
Measured: 3 years
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline oestradiol
During Visit 1, the research team will collect approx 20 ml of blood to measure oestradiol in pmol/L.
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-understanding steroidal activity in peripheral blood mononuclear cells.
During Visit 1, the research team will collect approx 63 ml of blood to extract peripheral blood mononuclear cells for further experiments to measure the impact of classic and 11-oxygenated androgen precursors on downstream steroid profile
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism- to study the changes in steroid levels over time in arterialized hand vein
Visit 2 to 4, the research team will collect blood samples (1-2ml each time) from arterialized hand vein to study the changes in steroid levels from -90 to 480 min at 30 min intervals
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism- to study the changes in steroid levels over time in abdominal vein
Visit 2 to 4, the research team will collect blood samples (1-2ml each time) from abdominal vein to study the changes in steroid levels from -90 to 480 min at 30 min intervals
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism to study the changes in salivary steroid levels over time
Visit 2 to 4, the research team will collect salivary samples (1-2ml each time) to study the changes in steroid levels at 0, 30, and 60 minutes and hourly thereafter until the end of Study Visits.
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-to study the changes in urinary steroid levels over time
Visit 2 to 4, the research team will collect urine from time point 0 to 480 minutes to study the changes in steroid levels
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline hormone levels for part B of the study
for Part B of the study, a blood sample (approx 7 ml) is collected from female volunteers undergoing elective abdominal surgery to establish baseline hormonal levels
Measured: 3 years
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism- to study the downstream conversion of steroid precursor in omental and subcutaneous fat
for Part B of the study, paired subcutaneous and omental adipose tissue samples (up to 5 g) are collected from female volunteers undergoing elective abdominal surgery.
- the concentration of classic and 11-oxygenated androgen metabolites (androstenedione, testosterone, dihydrotestosterone, 11-ketoandrostenedione, 11-hydroxyandrostenedione, 11-ketotestosterone, 11-hydroxytestosterone) will be measured in the culture medium by liquid chromatography tandem mass spectrometery in nmol/L.
- the relative abundance of all detectable metabolites will be determined by untargeted metabolomics using liquid chromatography tandem mass spectrometery.
- the tissue will be used for gene expression analysis: Quantitative PCR will be used to determination of the relative abundance of specific mRNA transcripts. RNAseq will be used to quantify the abundace of all mRNA transcripts of the transciptome.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2022
- Study start10 Oct 2021
- Primary completion31 Dec 2022 (estimated)
- Study completion30 May 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycystic Ovary SyndromeStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A prospective human in-vivo physiology study
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wiebke Arlt, Dsc, Principal investigator, Director, Institute of Metabolism and Systems Research (IMSR)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05246865
- Sponsor's protocol ID
- RG_19-038
- Acronym
- 11OXO-PCOS
- Status last verified
- Nov 2022
- First submitted
- 26 Jul 2019
- Last updated
- 2 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of 11-oxygenated Androgens in Androgen Excess and Metabolic Dysfunction of Women With Polycystic Ovary Syndrome
- ClinicalTrials.gov ID
- NCT05246865
- Acronym / sponsor ID
- 11OXO-PCOS / RG_19-038
- Conditions
- Polycystic Ovary Syndrome
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Study start
- 10 Oct 2021 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 30 May 2025 (estimated)
- First posted
- 18 Feb 2022 (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.
Polycystic ovary syndrome (PCOS) affects 10% of all women and usually presents with irregular menstrual periods and difficulties conceiving. It 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 (also termed 'insulin resistance'). Androgens circulating in the blood in women with PCOS are comprised of classic androgens (for example testosterone), and the less-characterised 11-oxygenated androgen subclass that arises from the adrenal glands. The investigators have recently demonstrated that 11-oxygenated androgens make up the majority of circulating androgens in women with PCOS.
In preliminary studies using minimally invasive adipose tissue sampling, the investigators have found that the fat tissue of women with PCOS overproduces classic androgens. This can lead directly to disturbances in the ability of fat cells to store fat effectively (lipotoxicity), resulting in insulin resistance and the consequent risk of liver damage. However, there are no published studies on in vivo androgen concentrations in the adipose tissue of women with PCOS. Furthermore, the scientific community do not have any information on whether adipose concentrations of 11-oxygenated androgens are also increased in women with PCOS.
Research Questions The investigators aim to examine the metabolism of classic and 11-oxygenated androgens in detail in both circulations and in the adipose tissue of women with PCOS. The investigators will examine how precursor variants of both 11-oxygenated and classic androgens, which are converted by the body into active hormones, are broken down (metabolised) within the adipose tissue of women with PCOS. The investigators will also investigate if the 11-oxygenated androgens have a differential impact on metabolic function as compared to classic androgens. This will give important insights into the adipose tissue metabolome in women with PCOS, and how locally generated androgens impact on adipose tissue function and metabolic risk.
Detailed description
In part A of the study, women with PCOS and obesity, identified from the previously established DAISy-PCOS cohort, and age- and BMI-matched healthy volunteers identified by advertisements, will be invited for a screening visit (Visit 1) at the National Institute of Health Research-Wellcome Trust Clinical Research Facility at the Queen Elizabeth Hospital Birmingham. Once eligibility (described in detail in Section 7.1) has been confirmed, a written informed consent will be obtained, and the volunteers will be invited to three further metabolic assessment visits after an overnight fast.
While Visits 2 and 3 (Study days 1 and 2, respectively) will be for the assessment of responses to an androgen-precursor challenge, Visit 4 (Study day 3) will run in the same format as the previous two Study days except no androgen will be administered. During each visit, study participants will undergo abdominal adipose tissue vein cannulation, whereby a catheter will be inserted (under ultrasound guidance and with local anaesthetic) into one of the veins of the abdominal fat tissue. Ultrasound Doppler and ethanol dilution by microdialysis will be employed to assess adipose tissue blood flow. A further catheter will be inserted into a vein on the back of the hand which will be placed a hot air box in order to obtain arterialised blood. Finally, a catheter will be inserted into an antecubital vein for the purposes of stable isotope infusion. Blood samples from the hand vein and from the abdominal adipose tissue vein will be taken in tandem every 30 minutes for measurement of various metabolites, androgens, and non-targeted metabolome studies. Salivary samples will be collected every 30 minutes in the first hour and hourly thereafter until the end of the study. Urine will be collected throughout the Study Visit. At time point 240 min, a standardised high-fat meal containing palmitate labelled with a stable isotope will be given to the participant, and measurements will continue, to assess how their metabolism responds to the meal. Furthermore, fat tissue biopsies will be taken from the subcutaneous abdominal adipose tissue at the end of each study day. These fat biopsies will undergo RNA extraction for transcriptional profiling by RNA-sequencing and will be used for tissue incubation to determine their androgen-generating and metabolic capacity.
On Visits 2 and 3, participants will be administered either the classic androgen pathway precursor dehydroepiandrosterone or the 11-oxygenated androgen pathway precursor 11-ketoandrostenedione at time point 0 min. No androgen precursors will be administered during Visit 4. Otherwise, Visits 2-4 will be identical in their flow.
In part B of the study, paired subcutaneous and omental adipose tissue samples (up to 5 g), as well as a blood sample, are collected from female volunteers undergoing elective abdominal surgery. These tissue samples alongside the subcutaneous tissue obtained from the in vivo study (part A) will be used for ex vivo incubations with androgen precursors to study androgen activation and its metabolic impact. Additionally, the effect of Aldo-Keto Reductase Family 1 Member C3 inhibition on androgen activation will be assessed in ex vivo incubations. After the incubation, the culture medium and/or the tissue will be used for metabolome analysis (non-targeted global metabolome and steroid metabolome profiling) and transcriptome analysis. The blood sample will be used for serum multi-steroid profiling.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A prospective human in-vivo physiology study
| Arm | Type | Receives |
|---|---|---|
| Women with PCOS | Experimental | Drug: oral androgen challenge with dehydroepiandrosterone (DHEA)Women with polycystic ovary syndrome |
| Age and BMI-matched healthy volunteers | Experimental | Drug: oral androgen challenge with dehydroepiandrosterone (DHEA)Otherwise healthy women without PCOS but matching in age and body mass index to the above group |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- BMI between 30-40 kg/m2
- Age range 18-40 years
- Ability to provide informed consent
- For women participating in the PCOS group, the diagnosis of PCOS will be established during their recruitment to DAISy-PCOS study on the basis of the Rotterdam Consensus Criteria for the Diagnosis of PCOS, as recommended by the current international PCOS guidelines (at least 2 out of 3 criteria):
- Androgen excess (clinical and/or biochemical evidence)
Key exclusion criteria (19 listed)
- Pregnancy or breastfeeding at the time of planned recruitment
- History of significant renal (eGFR<30) or hepatic impairment (aspartate aminotransferase or alanine transaminase >two-fold above ULN; pre-existing bilirubinaemia >1.2 ULN)
- Any other significant disease or disorder that, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
- 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 |
|---|---|---|
| oral androgen challenge with dehydroepiandrosterone (DHEA)Also: oral androgen challenge with 11-ketoandrostenedioneThe oral androgen challenge is a safe and well-validated means of studying the androgen generation profiles of different study groups. | Drug | Age and BMI-matched healthy volunteers, Women with PCOS |
Primary outcome
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline height
Time frame: 3 years
During Visit 1, the research team will measure height in centimetres
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline weight
Time frame: 3 years
During Visit 1, the research team will measure weight in kilogram
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline body mass index (BMI)
Time frame: 3 years
During Visit 1, weight and height will be combined to report BMI in kg/m^2
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline waist circumference
Time frame: 3 years
During Visit 1, the research team will measure Waist circumference to nearest centimetre
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline blood pressure
Time frame: 3 years
During Visit 1, the research team will measure both systolic and diastolic Blood pressure in mmHg after 10 minutes in sitting position
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline urea & electrolytes
Time frame: 3 years
During Visit 1, the research team will collect blood to measure urea \& electrolytes in mmol/L
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline liver function test
Time frame: 3 years
During Visit 1, the research team will collect blood to measure liver function tests in mmol/L
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline haemoglobin
Time frame: 3 years
During Visit 1, the research team will collect blood to measure haemoglobin in grams per litre
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline white cell and platelet count
Time frame: 3 years
During Visit 1, the research team will collect blood to measure White cell and platelets in number of cells per ml
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline lipid profile
Time frame: 3 years
During Visit 1, the research team will collect blood to measure lipid profile in mmol/L
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline glucose
Time frame: 3 years
During Visit 1, the research team will collect blood to measure glucose in mmol/L
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline glycated haemoglobin
Time frame: 3 years
During Visit 1, the research team will collect blood to measure glycated haemoglobin (HbA1c) in mmol/mol
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline thyroid function test
Time frame: 3 years
During Visit 1, the research team will collect blood to measure thyroid function test in mIU/L
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline Dehydroepiandrosterone (DHEAS)
Time frame: 3 years
During Visit 1, the research team will collect blood to measure DHEAS in µmol/L
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline androstenedione
Time frame: 3 years
During Visit 1, the research team will collect blood to measure androstenedione in µmol/L
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline testosterone
Time frame: 3 years
During Visit 1, the research team will collect blood to measure testosterone in nmol/L
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline sex hormone binding globulin
Time frame: 3 years
During Visit 1, the research team will collect blood to measure sex hormone binding globulin in nmol/L
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline 17-hydroxyprogesterone
Time frame: 3 years
During Visit 1, the research team will collect blood to measure 17-hydroxyprogesterone in nmol/L
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline prolactin
Time frame: 3 years
During Visit 1, the research team will collect blood to measure prolactin in mIU/L
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline Follicle-stimulating hormone
Time frame: 3 years
During Visit 1, the research team will collect blood to measure Follicle-stimulating hormone in IU/L
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline luteinizing hormone
Time frame: 3 years
During Visit 1, the research team will collect blood to measure luteinizing hormone in IU/L
overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline oestradiol
Time frame: 3 years
During Visit 1, the research team will collect approx 20 ml of blood to measure oestradiol in pmol/L.
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-understanding steroidal activity in peripheral blood mononuclear cells.
Time frame: 3 years
During Visit 1, the research team will collect approx 63 ml of blood to extract peripheral blood mononuclear cells for further experiments to measure the impact of classic and 11-oxygenated androgen precursors on downstream steroid profile
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism- to study the changes in steroid levels over time in arterialized hand vein
Time frame: 3 years
Visit 2 to 4, the research team will collect blood samples (1-2ml each time) from arterialized hand vein to study the changes in steroid levels from -90 to 480 min at 30 min intervals
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism- to study the changes in steroid levels over time in abdominal vein
Time frame: 3 years
Visit 2 to 4, the research team will collect blood samples (1-2ml each time) from abdominal vein to study the changes in steroid levels from -90 to 480 min at 30 min intervals
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism to study the changes in salivary steroid levels over time
Time frame: 3 years
Visit 2 to 4, the research team will collect salivary samples (1-2ml each time) to study the changes in steroid levels at 0, 30, and 60 minutes and hourly thereafter until the end of Study Visits.
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-to study the changes in urinary steroid levels over time
Time frame: 3 years
Visit 2 to 4, the research team will collect urine from time point 0 to 480 minutes to study the changes in steroid levels
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline hormone levels for part B of the study
Time frame: 3 years
for Part B of the study, a blood sample (approx 7 ml) is collected from female volunteers undergoing elective abdominal surgery to establish baseline hormonal levels
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism- to study the downstream conversion of steroid precursor in omental and subcutaneous fat
Time frame: 3 years
for Part B of the study, paired subcutaneous and omental adipose tissue samples (up to 5 g) are collected from female volunteers undergoing elective abdominal surgery. * the concentration of classic and 11-oxygenated androgen metabolites (androstenedione, testosterone, dihydrotestosterone, 11-ketoandrostenedione, 11-hydroxyandrostenedione, 11-ketotestosterone, 11-hydroxytestosterone) will be measured in the culture medium by liquid chromatography tandem mass spectrometery in nmol/L. * the relative abundance of all detectable metabolites will be determined by untargeted metabolomics using liquid chromatography tandem mass spectrometery. * the tissue will be used for gene expression analysis: Quantitative PCR will be used to determination of the relative abundance of specific mRNA transcripts. RNAseq will be used to quantify the abundace of all mRNA transcripts of the transciptome.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2022.
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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. This study is not recruiting at the moment.
Wiebke Arlt, Dsc principal investigator
Director, Institute of Metabolism and Systems Research (IMSR)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing oral androgen challenge with dehydroepiandrosterone (DHEA) in people with Polycystic Ovary Syndrome, run by University of Birmingham at 1 site in United Kingdom.
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 7 inclusion and 19 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 2 Nov 2022. 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 United Kingdom. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Punith Kempegowda, MD MRCP (+441214147525, p.kempegowda@bham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The impact of classic and 11-oxygenated androgen precursors on systemic circulation of overall steroid profile and its impact on lipid and glucose metabolism-establishing baseline height (time frame: 3 years). The study lists 29 primary outcomes in all. 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 Nov 2022.