REFUEL PCOS Study 1

NCT05973175 | Recruiting DMC

• 1 other identifier: REC 22/28
• Study Type: observational
• Target: 40
• 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 male pattern hormones (also termed androgens). 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 results in increased metabolic complications observed in women with PCOS. The main aims of the REFUEL PCOS study are to compare markers of energy metabolism in women with PCOS to those without PCOS. This will allow the investigators to better understand metabolic risk by examining the relationship between androgen excess and energy metabolism. Skeletal muscle is an important site of energy metabolism, and emerging theories are that androgen excess impairs skeletal muscle energy balance and increases the risk of complications. Based on these emerging theories, the investigators want to investigate the effects of androgens on muscle energy metabolism. The investigators will also examine whether certain blood and urine result patterns can help identify differences in muscles energy metabolism and which women are at the highest risk of metabolic complications. This research will give insight into the metabolic risk associated with PCOS and treat and, where possible, prevent the development of metabolic disease in affected women.

Conditions

Polycystic Ovary Syndrome

Outcome Measures

Primary Outcomes (1)

• To delineate the relationship between androgen excess and skeletal muscle energy metabolism in women

  Baseline differences in the skeletal muscle proteome and differentially regulated pathways relating to mitochondrial function in hyperandrogenic women with PCOS compared to healthy controls

  2.5 years

Secondary Outcomes (1)

• Proteomic profiling of skeletal muscle biopsies will be integrated with serum steroid and non-targeted metabolome data to delineate the relationship between androgens and skeletal muscle energy metabolism in women

  2.5 years

Study Arms (2)

Women with PCOS

The following inclusion criteria need to be met for the PCOS Study participants: * Women with a confirmed diagnosis polycystic ovary syndrome with androgen excess on clinical or biochemical grounds * BMI 20-40kg/m2 * Age range 18-50 years * Ability to provide informed consent

Women without PCOS (controls)

The following inclusion criteria need to be met for the control Study participants: * No clinical features of possible polycystic ovary syndrome (absence of clinical features of androgen excess and ovulatory dysfunction). * BMI 20-40kg/m2 * Age range 18-50 years * Ability to provide informed consent

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Studying a female reproductive condition
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

This study aims to recruit women with PCOS who have a BMI between 20 and 40kg/m2 with clinical or biochemical evidence of androgen excess. Their matched controls will have no clinical features of possible polycystic ovary syndrome (absence of clinical features of androgen excess and ovulatory dysfunction).

You may qualify if:

• Women with a confirmed diagnosis polycystic ovary syndrome with androgen excess on clinical or biochemical grounds
• BMI 20-40kg/m2
• Age range 18-50 years
• Ability to provide informed consent
• No clinical features of possible polycystic ovary syndrome (absence of clinical features of androgen excess and ovulatory dysfunction).
• BMI 20.0-40kg/m2
• Age range 18-50 years
• Ability to provide informed consent
• For participants with PCOS, a diagnosis of PCOS should be established on the basis of the Androgen Excess and PCOS (AE-PCOS) Society guidelines:
• Androgen excess (clinical and/or biochemical evidence)
• Chronic oligo-/anovulation (clinical and/or biochemical evidence)

You may not qualify if:

• The participant may not enter the study if ANY of the following apply:
• 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

Sponsors & Collaborators

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

Study Sites (1)

Royal Collage Of Surgeons

Dublin, Ireland

RECRUITING

Related Publications (15)

• Riestenberg C, Jagasia A, Markovic D, Buyalos RP, Azziz R. Health Care-Related Economic Burden of Polycystic Ovary Syndrome in the United States: Pregnancy-Related and Long-Term Health Consequences. J Clin Endocrinol Metab. 2022 Jan 18;107(2):575-585. doi: 10.1210/clinem/dgab613.

  PMID: 34546364 BACKGROUND

• Schiffer L, Arlt W, O'Reilly MW. Understanding the Role of Androgen Action in Female Adipose Tissue. Front Horm Res. 2019;53:33-49. doi: 10.1159/000494901. Epub 2019 Sep 9.

  PMID: 31499495 BACKGROUND

• Nanba AT, Rege J, Ren J, Auchus RJ, Rainey WE, Turcu AF. 11-Oxygenated C19 Steroids Do Not Decline With Age in Women. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2615-2622. doi: 10.1210/jc.2018-02527.

  PMID: 30753518 BACKGROUND

• Kumarendran B, O'Reilly MW, Manolopoulos KN, Toulis KA, Gokhale KM, Sitch AJ, Wijeyaratne CN, Coomarasamy A, Arlt W, Nirantharakumar K. Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database. PLoS Med. 2018 Mar 28;15(3):e1002542. doi: 10.1371/journal.pmed.1002542. eCollection 2018 Mar.

  PMID: 29590099 BACKGROUND

• Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, Welt CK; Endocrine Society. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013 Dec;98(12):4565-92. doi: 10.1210/jc.2013-2350. Epub 2013 Oct 22.

  PMID: 24151290 BACKGROUND

• Randeva HS, Tan BK, Weickert MO, Lois K, Nestler JE, Sattar N, Lehnert H. Cardiometabolic aspects of the polycystic ovary syndrome. Endocr Rev. 2012 Oct;33(5):812-41. doi: 10.1210/er.2012-1003. Epub 2012 Jul 24.

  PMID: 22829562 BACKGROUND

• Kempegowda P, Melson E, Manolopoulos KN, Arlt W, O'Reilly MW. Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2020 Jun 24;11:2042018820934319. doi: 10.1177/2042018820934319. eCollection 2020.

  PMID: 32637065 BACKGROUND

• Subramanian A, Anand A, Adderley NJ, Okoth K, Toulis KA, Gokhale K, Sainsbury C, O'Reilly MW, Arlt W, Nirantharakumar K. Increased COVID-19 infections in women with polycystic ovary syndrome: a population-based study. Eur J Endocrinol. 2021 May;184(5):637-645. doi: 10.1530/EJE-20-1163.

  PMID: 33635829 BACKGROUND

• Barry JA, Kuczmierczyk AR, Hardiman PJ. Reporting the rates of depression in polycystic ovary syndrome (PCOS). J Sex Med. 2014 Jul;11(7):1882-3. doi: 10.1111/jsm.12503. Epub 2014 Mar 17. No abstract available.

  PMID: 24636134 BACKGROUND

• Barry JA, Azizia MM, Hardiman PJ. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2014 Sep-Oct;20(5):748-58. doi: 10.1093/humupd/dmu012. Epub 2014 Mar 30.

  PMID: 24688118 BACKGROUND

• O'Reilly MW, Kempegowda P, Jenkinson C, Taylor AE, Quanson JL, Storbeck KH, Arlt W. 11-Oxygenated C19 Steroids Are the Predominant Androgens in Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2017 Mar 1;102(3):840-848. doi: 10.1210/jc.2016-3285.

  PMID: 27901631 BACKGROUND

• Escobar-Morreale HF, Alvarez-Blasco F, Botella-Carretero JI, Luque-Ramirez M. The striking similarities in the metabolic associations of female androgen excess and male androgen deficiency. Hum Reprod. 2014 Oct 10;29(10):2083-91. doi: 10.1093/humrep/deu198. Epub 2014 Aug 7.

  PMID: 25104855 BACKGROUND

• O'Reilly MW, House PJ, Tomlinson JW. Understanding androgen action in adipose tissue. J Steroid Biochem Mol Biol. 2014 Sep;143:277-84. doi: 10.1016/j.jsbmb.2014.04.008. Epub 2014 Apr 28.

  PMID: 24787657 BACKGROUND

• Nilsson E, Benrick A, Kokosar M, Krook A, Lindgren E, Kallman T, Martis MM, Hojlund K, Ling C, Stener-Victorin E. Transcriptional and Epigenetic Changes Influencing Skeletal Muscle Metabolism in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2018 Dec 1;103(12):4465-4477. doi: 10.1210/jc.2018-00935.

  PMID: 30113663 BACKGROUND

• Skiba MA, Islam RM, Bell RJ, Davis SR. Understanding variation in prevalence estimates of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2018 Nov 1;24(6):694-709. doi: 10.1093/humupd/dmy022.

  PMID: 30059968 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Routine blood (cholesterol profile, HbA1C, LFTs, FBC, Renal profile) will be sent to the laboratory in the Beaumont Hospital for processing on the same day of sampling. Samples for steroid nontargeted metabolomics and muscle biopsy specimens will be stored in a -80C freezer in the research laboratory in the CRC building until analysis. Serum samples for targeted nontargeted metabolomics will be measured and analysed at the University of Birmingham by LC-MS/MS. Muscle biopsy specimens will undergo proteomic sequencing at the University College Dublin and metabolomic analysis at the University of Liverpool. The blood volume that will be collected is approximately 350ml. The amount collected for skeletal muscle tissue biopsies will be similar to half a grain of rice for each biopsies.

MeSH Terms

Conditions

Polycystic Ovary Syndrome

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

Central Study Contacts

Michael W O'Reilly, FRCPI PhD

CONTACT

018093894; michaelworeilly@rcsi.ie

Leanne Cussen, mb bch bao

CONTACT

0871344858; leannecussen@rcsi.ie

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2023
• First Posted: August 2, 2023
• Study Start: August 1, 2023
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: April 17, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 6 months following publication
• Access Criteria: To ensure due process and aid sharing of the data the study will be registered online at (https://clinicaltrials.gov). Data will be shared upon request in keeping with Wellcome policy and as per REC guidance at the time of request post-publication of results.

Locations

IE (1)