Dissecting the IMpact of 11-OXygenated and Classic Androgens on Skeletal Muscle Insulin Sensitivity (DIMOXIS)

NCT05263557 | Unknown DMC

• 1 other identifier: DIMOXIS
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Androgen excess is the cardinal biochemical feature of polycystic ovary syndrome (PCOS). Serum testosterone correlates with insulin resistance in PCOS, however, there is an urgent need to improve our understanding of the association between androgens and the risk of type 2 diabetes. 11-oxygenated steroids are the predominant androgens in PCOS and 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 Crucially, there are no data linking androgen excess with muscle glucose metabolism and the differential contribution of 11-oxygenated androgens to diabetes risk through these processes remains unknown. The investigators hypothesise the following:

1. 1.Oral androgen exposure in women with PCOS results in distinct changes in tissue-specific insulin sensitivity and muscle energy biogenesis
2. 2.11-oxygenated androgen exposure exerts differential changes on the above parameters in comparison to classic androgen exposure
3. 3.To examine the impact of oral androgen exposure on skeletal muscle insulin sensitivity and glucose disposal in women with PCOS.
4. 4.To delineate the impact of androgen exposure on muscle mitochondrial function ex vivo in women with PCOS
5. 5.To compare the differential impact of 11-oxygenated androgen compared to classic androgens on glucose disposal and muscle mitochondrial function

Conditions

Polycystic Ovary Syndrome; Insulin Resistance; Androgen; Hypersecretion; Endocrine System Diseases

Keywords

PCOS

Outcome Measures

Primary Outcomes (1)

• Relative change in glucose disposal from baseline with 11KA4 administration compared to that seen with DHEA

  Utilizing hyperglycaemic-euglycaemic clamp (μmol/min/kg)

  7 Days

Secondary Outcomes (2)

• Relative change in glucose oxidation from baseline with 11KA4 administration compared to that seen with DHEA

  7 Days

• Relative change in endogenous glucose production from baseline with 11KA4 administration compared to that seen with DHEA (μmol/min/kg)

  7 Days

Study Arms (2)

DHEA

EXPERIMENTAL

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

Dietary Supplement: Dehydroepiandrosterone (DHEA)

11KA4

EXPERIMENTAL

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

Dietary Supplement: 11-ketoandrostenedione (11KA4)

Interventions

Dehydroepiandrosterone (DHEA) DIETARY_SUPPLEMENT

Dehydroepiandrosterone (DHEA) at a dose of 150mg once daily for 7 days.

DHEA

11-ketoandrostenedione (11KA4) DIETARY_SUPPLEMENT

11ketoandrostenedione (11KA4) at a doses of 150mg once daily for 7 days.

11KA4

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women with a confirmed diagnosis polycystic ovary syndrome with androgen excess on clinical or biochemical grounds
• BMI 20.0-39.9kg/m2
• Age range 18-40 years
• Ability to provide informed consent

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 3-months)
• Blood haemoglobin \<12.0g/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 or Treatment with anticoagulant agents
• 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.
• 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

Sponsors & Collaborators

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

Study Sites (1)

Beaumont Hospital

Dublin, Ireland

RECRUITING

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Insulin Resistance; Endocrine System Diseases

Interventions

Dehydroepiandrosterone; adrenosterone

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; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 17-Ketosteroids; Ketosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Study Officials

• Michael W Michael

  RCSI Education & Research Centre, Beaumont Hospital, Beaumont Dublin 9 Ireland Ireland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael W O'Reilly

CONTACT

018093894; michaelworeilly@rcsi.ie

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Interventional

Study Record Dates

• First Submitted: October 20, 2021
• First Posted: March 2, 2022
• Study Start: August 19, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: July 25, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)