Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05263557
Other study ID # DIMOXIS
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date August 19, 2022
Est. completion date December 2024

Study information

Verified date June 2023
Source Royal College of Surgeons, Ireland
Contact Michael W O'Reilly
Phone 018093894
Email michaelworeilly@rcsi.ie
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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. Oral androgen exposure in women with PCOS results in distinct changes in tissue-specific insulin sensitivity and muscle energy biogenesis 2. 11-oxygenated androgen exposure exerts differential changes on the above parameters in comparison to classic androgen exposure The study has the following aims: 1. To examine the impact of oral androgen exposure on skeletal muscle insulin sensitivity and glucose disposal in women with PCOS. 2. To delineate the impact of androgen exposure on muscle mitochondrial function ex vivo in women with PCOS 3. To compare the differential impact of 11-oxygenated androgen compared to classic androgens on glucose disposal and muscle mitochondrial function The two arms will run in parallel and all participants will undergo identical investigations before and after 7 days of either DHEA or 11KA4. Investigations will include baseline arthrometric measurements muscle biopsy, two-step hyperinsulinaemic euglycaemic clamp, breath sampling. This interventional metabolic phenotyping study will probe the role of classic and 11-oxygenated androgens in metabolic dysfunction in PCOS using gold-standard in vivo metabolic phenotyping techniques. Delineating the distinct contribution of 11-oxygenated androgens, through effects on skeletal muscle biology, to the risk of T2DM is an important step in the process of determining risk of type 2 diabetes in this vulnerable cohort.


Recruitment information / eligibility

Status Recruiting
Enrollment 20
Est. completion date December 2024
Est. primary completion date December 2024
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Female
Age group 18 Years to 40 Years
Eligibility Inclusion Criteria: - 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 Exclusion Criteria: - 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

Study Design


Intervention

Dietary Supplement:
Dehydroepiandrosterone (DHEA)
Dehydroepiandrosterone (DHEA) at a dose of 150mg once daily for 7 days.
11-ketoandrostenedione (11KA4)
11ketoandrostenedione (11KA4) at a doses of 150mg once daily for 7 days.

Locations

Country Name City State
Ireland Beaumont Hospital Dublin 9

Sponsors (3)

Lead Sponsor Collaborator
Royal College of Surgeons, Ireland University of Birmingham, University of Oxford

Country where clinical trial is conducted

Ireland, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Relative change in glucose oxidation from baseline with 11KA4 administration compared to that seen with DHEA Measured by 13C-breath testing (mg/kg/min) 7 Days
Secondary Relative change in endogenous glucose production from baseline with 11KA4 administration compared to that seen with DHEA (µmol/min/kg) Utilizing hyperglycaemic-euglycaemic clamp (µmol/min/kg) 7 Days
See also
  Status Clinical Trial Phase
Completed NCT03142633 - MicroRNA as Biomarkers for Development of Metabolic Syndrome in Women With Polycystic Ovary Syndrome
Recruiting NCT04984226 - Sodium Bicarbonate and Mitochondrial Energetics in Persons With CKD Phase 2
Recruiting NCT05354245 - Using a Complex Carbohydrate Mixture to Steer Fermentation and Improve Metabolism in Adults With Overweight and Prediabetes (DISTAL) N/A
Completed NCT03383822 - Regulation of Endogenous Glucose Production by Brain Insulin Action in Insulin Resistance Phase 1/Phase 2
Recruiting NCT06007404 - Understanding Metabolism and Inflammation Risks for Diabetes in Adolescents
Suspended NCT03652987 - Endocrine and Menstrual Disturbances in Women With Polycystic Ovary Syndrome (PCOS)
Completed NCT04203238 - Potato Research for Enhancing Metabolic Outcomes N/A
Recruiting NCT03658564 - Preoperative Oral Carbohydrate Treatment Minimizes Insulin Resistance N/A
Completed NCT04183257 - Effect of Escalating Oral Vitamin D Replacement on HOMA-IR in Vitamin D Deficient Type 2 Diabetics Phase 4
Completed NCT04117802 - Effects of Maple Syrup on Gut Microbiota Diversity and Metabolic Syndrome N/A
Completed NCT03627104 - Effect of Dietary Protein and Energy Restriction in the Improvement of Insulin Resistance in Subjects With Obesity N/A
Completed NCT05124847 - TREating Pediatric Obesity N/A
Active, not recruiting NCT03288025 - Pulmonary Arterial Hypertension Improvement With Nutrition and Exercise (PHINE) N/A
Completed NCT03809182 - Effect of Dexmedetomidine on Postoperative Glucose and Insulin Levels. Phase 4
Completed NCT01809288 - Identifying Risk for Diabetes and Heart Disease in Women
Completed NCT04642482 - Synbiotic Therapy on Intestinal Microbiota and Insulin Resistance in Obesity Phase 4
Terminated NCT03278236 - Does Time Restricted Feeding Improve Glycaemic Control in Overweight Men? N/A
Not yet recruiting NCT06159543 - The Effects of Fresh Mango Consumption on Cardiometabolic Outcomes in Free-living Individuals With Prediabetes N/A
Not yet recruiting NCT05540249 - Pre-operative Carbohydrates in Diabetic Patients Undergoing CABG N/A
Withdrawn NCT04741204 - Metformin Use to Reduce Disparities in Newly Diagnosed Breast Cancer Phase 4