The RolE oF Androgen Excess in MUscle Energy MetaboLism in Women With PolyCystic Ovary Syndrome (REFUEL PCOS) Study 2

NCT05647356 | Unknown DMC

• 1 other identifier: 22/52
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Polycystic Ovary Syndrome; Androgen Excess; Metabolic Disease

Outcome Measures

Primary Outcomes (1)

• 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

  2.5 years

Secondary Outcomes (3)

• To determine the relationship between androgen excess and serum/muscle non-targeted metabolomics

  2.5 years

• To determine the impact of androgen receptor blockade on skeletal muscle mitochondrial morphology and function ex vivo

  2.5 years

• To determine the impact of androgen receptor blockade on skeletal muscle mitochondrial morphology and function ex vivo

  2.5

Study Arms (1)

Bicalutamide

EXPERIMENTAL

Adult females with polycystic ovary syndrome (PCOS) and evidence of clinical or biochemical androgen excess will be recruited.

Drug: Bicalutamide 50 mg

Interventions

Bicalutamide 50 mg DRUG

Bicalutamide at a dose of 50mg once daily for 28 days.

Bicalutamide

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Women with a confirmed diagnosis of polycystic ovary syndrome with androgen excess on clinical or biochemical grounds
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Royal College of Surgeons, Ireland: lead
• University of Birmingham: collaborator
• University of Liverpool: collaborator
• University of Oxford: collaborator
• University College Dublin: collaborator

Study Sites (1)

Royal Collage Of Surgeons

Dublin, Ireland

Location

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Hyperandrogenism; Metabolic Diseases

Interventions

bicalutamide

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; 46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Adrenogenital Syndrome; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 2, 2022
• First Posted: December 12, 2022
• Study Start: January 1, 2023
• Primary Completion: April 1, 2025
• Study Completion: September 1, 2025
• Last Updated: December 12, 2022

Record last verified: 2022-12

Locations

IE (1)