Polycystic Ovary SyndromeREFUEL PCOSNCT05647356
The RolE oF Androgen Excess in MUscle Energy MetaboLism in Women With PolyCystic Ovary Syndrome (REFUEL PCOS) Study 2
A study testing Bicalutamide 50 mg in people with Polycystic Ovary Syndrome and Androgen Excess, run by Royal College of Surgeons, Ireland at 1 site in Ireland.
Trial summary
Polycystic ovary syndrome (PCOS) affects 10% of all women, and it usually co-exists with high levels of sex hormones called androgens, such as testosterone. Women with PCOS are at increased risk of metabolic complications such as diabetes, non-alcoholic fatty liver disease, high blood pressure and heart disease. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome, Androgen Excess, Metabolic Disease
- What is being tested?
- Bicalutamide 50 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteIreland
- Study dates
- 1 Jan 2023to 1 Sep 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
- No healthy volunteers
- Adult
Who may be able to join
- Women with a confirmed diagnosis of polycystic ovary syndrome with androgen excess on clinical or biochemical grounds
- BMI 20-40kg/m2
- Age range 18-40 years
- Ability to provide informed consent
- Negative pregnancy test at screening
- Effective method of contraception (will sign a pregnancy waiver)
Who cannot join
- A confirmed diagnosis of diabetes
- Current or recent (<3 months) use of weight loss medications
- Current or recent use of oral contraceptive pill or hormone replacement therapy (within last 3-months)
- Blood haemoglobin <11.0g/dL
- History of alcoholism or a greater than recommended alcohol intake (recommendations > 21 units on average per week for men and > 14 units on average per week for women)
- Haemorrhagic disorders
Show all 18Show fewer
- Treatment with anticoagulant agents
- Other co-morbidities that in the view of the investigators may affect data collection
- Any medical condition in the opinion of the investigator that might impact upon safety or validity of the results
- Pregnancy or breastfeeding at the time of planned recruitment
- A diagnosis of PCOS according to Rotterdam criteria where the patient does not have clinical or biochemical evidence of androgen excess
- History of significant renal (eGFR<30) or hepatic impairment (AST or ALT >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 three 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 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
Trial locations and contacts
1 site in 1 country.
About this study
Polycystic ovary syndrome (PCOS) affects 10% of all women, and it usually co-exists with high levels of sex hormones called androgens, such as testosterone. Women with PCOS are at increased risk of metabolic complications such as diabetes, non-alcoholic fatty liver disease, high blood pressure and heart disease. However, very little is understood about how androgen excess may drive the metabolic complications observed in women with PCOS.
Skeletal muscle is an important site of energy metabolism; increasingly, it is suspected that skeletal muscle energy balance is adversely impacted by androgens, thereby driving metabolic complications. To take this theory forward, we want to investigate the effects of androgens on muscle energy metabolism. We will perform detailed metabolic testing (including blood tests and muscle biopsies) in women with PCOS before and after taking tablets that block the action of testosterone for 28 days. In addition, we will be using a gold standard technique to see how women with PCOS metabolise fat and other nutrients by measuring markers in blood and breath samples after a breakfast test meal. This clinical research will increase our understanding of the complex relationships between hormonal abnormalities and metabolic disease in women with PCOS.
Read the detailed description
Background:
Polycystic ovary syndrome (PCOS) is a lifelong metabolic disorder affecting 10-13% of all women and is associated with major healthcare and economic burden, estimated at $8 billion annually the US in 2020. Traditionally considered a reproductive disorder only, it is now increasingly clear that PCOS is associated with severe metabolic health consequences across the entire life course of women. There is a two-fold increased risk of type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease, and emerging evidence of increased cardiovascular disease (CVD) incidence. There are no disease-specific therapies to mitigate or treat metabolic risk in women with PCOS. This is consistently highlighted as the priority concern amongst PCOS patient advocacy groups.
Androgen excess is a cardinal feature of PCOS, and circulating androgen burden is closely correlated with metabolic complications. In women with PCOS, the risk of developing metabolic dysfunction is above that conferred by simple obesity, suggesting that androgen excess is a key player; however, a distinct mechanistic role for androgens in this process remains to be elucidated. Androgen excess is associated with metabolically deleterious visceral fat accumulation and circulating testosterone levels correlate directly with the risk of T2DM and NAFLD. Muscle is a critical metabolic target tissue that plays a central role in energy metabolism through processes such as glucose uptake and oxidation, as well as oxidation of fatty acids to generate ATP in the mitochondria. Recent mechanistic data have shown that androgen excess is associated with changes in the transcriptional profile of skeletal muscle genes linked with metabolism and energy balance. Therefore, skeletal muscle is likely to represent an important site of crosstalk between androgen excess, disturbances in energy metabolism and risk of metabolic disease in PCOS.
Defective skeletal muscle glucose uptake is a key early step in the pathogenesis of insulin resistance in PCOS, and an early predictor of progression to overt type 2 diabetes mellitus. Impaired mitochondrial oxidation of free fatty acids in skeletal muscle and other disturbances in skeletal muscle mitochondrial function, such as oxidative phosphorylation, are increasingly implicated in the pathogenesis of metabolic disease such as T2DM. Abnormalities in skeletal muscle mitochondrial function have also been identified in small-scale studies in women with PCOS, and were associated with impaired fatty acid oxidation, weight gain and an increased risk of diabetes.
We hypothesise that androgen-mediated disturbances in skeletal muscle energy balance play a major role in the pathogenesis of metabolic disease in women with PCOS.
Study description:
We propose to test our hypothesis utilising state-of-the-art metabolic phenotyping tools in two study visits. We will examine systemic fatty acid oxidation, muscle proteomics and targeted and non-targeted metabolomics in women with PCOS before and after pharmacological androgen receptor blocade. In addition, a subset of ex vivo muscle biopsies will undergo in vitro experiments to measure skeletal muscle mitochondrial morphology and function.
After study visit 1, all recruited participants will receive 50mg of an oral androgen receptor antagonist (bicalutamide), resulting in pharmacological AR blockade, before undertaking an identical study visit for repeat assessment.
- Being tested
- Bicalutamide 50 mg
- Medical subject headings
- Polycystic Ovary Syndrome, Hyperandrogenism, Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bicalutamide 50 mgDrug
Bicalutamide at a dose of 50mg once daily for 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Bicalutamide | Experimental | Adult females with polycystic ovary syndrome (PCOS) and evidence of clinical or biochemical androgen excess will be recruited. Receives: Drug: Bicalutamide 50 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
To examine the impact of androgen receptor blockade (AR) on systemic and muscle-specific energy metabolism in women with PCOS and androgen excess
Change in whole body fatty acid oxidation on stable isotope breath after 28 days of androgen receptor (AR) blockade compared to baseline
Measured: 2.5 years
Secondary outcomes (3)
To determine the relationship between androgen excess and serum/muscle non-targeted metabolomics
Changes in metabolomic pathways relating to energy balance and mitochondrial function in serum and muscle after AR blockade
Measured: 2.5 years
To determine the impact of androgen receptor blockade on skeletal muscle mitochondrial morphology and function ex vivo
Changes in mitochondrial morphology ex vivo post AR blockade
Measured: 2.5 years
To determine the impact of androgen receptor blockade on skeletal muscle mitochondrial morphology and function ex vivo
Differences in mitochondrial oxygen consumption and oxidative phosphorylation using Seahorse technology pre and post AR blockade
Measured: 2.5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2022
- Study start1 Jan 2023 (estimated)
- Primary completion1 Apr 2025 (estimated)
- Study completion1 Sep 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal College of Surgeons, Ireland
- Sponsor type
- University, hospital or other
- Collaborators
- University of Birmingham, University of Liverpool, University of Oxford, University College Dublin
- Responsible party
- Principal investigator, Michael W, Royal College of Surgeons, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05647356
- Sponsor's protocol ID
- 22/52
- Acronym
- REFUEL PCOS
- Status last verified
- Dec 2022
- First submitted
- 2 Dec 2022
- Last updated
- 12 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The RolE oF Androgen Excess in MUscle Energy MetaboLism in Women With PolyCystic Ovary Syndrome (REFUEL PCOS) Study 2
- ClinicalTrials.gov ID
- NCT05647356
- Acronym / sponsor ID
- REFUEL PCOS / 22/52
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Royal College of Surgeons, IrelandUniversity, hospital or other
- Collaborators
- University of Birmingham, University of Liverpool, University of Oxford, University College Dublin
- Study start
- 1 Jan 2023 (estimated)
- Primary completion
- 1 Apr 2025 (estimated)
- Study completion
- 1 Sep 2025 (estimated)
- First posted
- 12 Dec 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 it usually co-exists with high levels of sex hormones called androgens, such as testosterone. Women with PCOS are at increased risk of metabolic complications such as diabetes, non-alcoholic fatty liver disease, high blood pressure and heart disease. However, very little is understood about how androgen excess may drive the metabolic complications observed in women with PCOS.
Skeletal muscle is an important site of energy metabolism; increasingly, it is suspected that skeletal muscle energy balance is adversely impacted by androgens, thereby driving metabolic complications. To take this theory forward, we want to investigate the effects of androgens on muscle energy metabolism. We will perform detailed metabolic testing (including blood tests and muscle biopsies) in women with PCOS before and after taking tablets that block the action of testosterone for 28 days. In addition, we will be using a gold standard technique to see how women with PCOS metabolise fat and other nutrients by measuring markers in blood and breath samples after a breakfast test meal. This clinical research will increase our understanding of the complex relationships between hormonal abnormalities and metabolic disease in women with PCOS.
Detailed description
Background:
Polycystic ovary syndrome (PCOS) is a lifelong metabolic disorder affecting 10-13% of all women and is associated with major healthcare and economic burden, estimated at $8 billion annually the US in 2020. Traditionally considered a reproductive disorder only, it is now increasingly clear that PCOS is associated with severe metabolic health consequences across the entire life course of women. There is a two-fold increased risk of type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease, and emerging evidence of increased cardiovascular disease (CVD) incidence. There are no disease-specific therapies to mitigate or treat metabolic risk in women with PCOS. This is consistently highlighted as the priority concern amongst PCOS patient advocacy groups.
Androgen excess is a cardinal feature of PCOS, and circulating androgen burden is closely correlated with metabolic complications. In women with PCOS, the risk of developing metabolic dysfunction is above that conferred by simple obesity, suggesting that androgen excess is a key player; however, a distinct mechanistic role for androgens in this process remains to be elucidated. Androgen excess is associated with metabolically deleterious visceral fat accumulation and circulating testosterone levels correlate directly with the risk of T2DM and NAFLD. Muscle is a critical metabolic target tissue that plays a central role in energy metabolism through processes such as glucose uptake and oxidation, as well as oxidation of fatty acids to generate ATP in the mitochondria. Recent mechanistic data have shown that androgen excess is associated with changes in the transcriptional profile of skeletal muscle genes linked with metabolism and energy balance. Therefore, skeletal muscle is likely to represent an important site of crosstalk between androgen excess, disturbances in energy metabolism and risk of metabolic disease in PCOS.
Defective skeletal muscle glucose uptake is a key early step in the pathogenesis of insulin resistance in PCOS, and an early predictor of progression to overt type 2 diabetes mellitus. Impaired mitochondrial oxidation of free fatty acids in skeletal muscle and other disturbances in skeletal muscle mitochondrial function, such as oxidative phosphorylation, are increasingly implicated in the pathogenesis of metabolic disease such as T2DM. Abnormalities in skeletal muscle mitochondrial function have also been identified in small-scale studies in women with PCOS, and were associated with impaired fatty acid oxidation, weight gain and an increased risk of diabetes.
We hypothesise that androgen-mediated disturbances in skeletal muscle energy balance play a major role in the pathogenesis of metabolic disease in women with PCOS.
Study description:
We propose to test our hypothesis utilising state-of-the-art metabolic phenotyping tools in two study visits. We will examine systemic fatty acid oxidation, muscle proteomics and targeted and non-targeted metabolomics in women with PCOS before and after pharmacological androgen receptor blocade. In addition, a subset of ex vivo muscle biopsies will undergo in vitro experiments to measure skeletal muscle mitochondrial morphology and function.
After study visit 1, all recruited participants will receive 50mg of an oral androgen receptor antagonist (bicalutamide), resulting in pharmacological AR blockade, before undertaking an identical study visit for repeat assessment.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bicalutamide | Experimental | Drug: Bicalutamide 50 mgAdult females with polycystic ovary syndrome (PCOS) and evidence of clinical or biochemical androgen excess will be recruited. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Women with a confirmed diagnosis of polycystic ovary syndrome with androgen excess on clinical or biochemical grounds
- BMI 20-40kg/m2
- Age range 18-40 years
- Ability to provide informed consent
- Negative pregnancy test at screening
Key exclusion criteria (18 listed)
- A confirmed diagnosis of diabetes
- Current or recent (<3 months) use of weight loss medications
- Current or recent use of oral contraceptive pill or hormone replacement therapy (within last 3-months)
- Blood haemoglobin <11.0g/dL
- History of alcoholism or a greater than recommended alcohol intake (recommendations > 21 units on average per week for men and > 14 units on average per week for women)
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 |
|---|---|---|
| Bicalutamide 50 mgBicalutamide at a dose of 50mg once daily for 28 days. | Drug | Bicalutamide |
Primary outcome
To examine the impact of androgen receptor blockade (AR) on systemic and muscle-specific energy metabolism in women with PCOS and androgen excess
Time frame: 2.5 years
Change in whole body fatty acid oxidation on stable isotope breath after 28 days of androgen receptor (AR) blockade compared to baseline
3 secondary outcomes
To determine the relationship between androgen excess and serum/muscle non-targeted metabolomics
Time frame: 2.5 years
To determine the impact of androgen receptor blockade on skeletal muscle mitochondrial morphology and function ex vivo
Time frame: 2.5 years
To determine the impact of androgen receptor blockade on skeletal muscle mitochondrial morphology and function ex vivo
Time frame: 2.5
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bicalutamide 50 mg in people with Polycystic Ovary Syndrome and Androgen Excess, 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 6 inclusion and 18 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 12 Dec 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To examine the impact of androgen receptor blockade (AR) on systemic and muscle-specific energy metabolism in women with PCOS and androgen excess (time frame: 2.5 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 12 Dec 2022.