Polycystic Ovary SyndromeDIMOXISNCT05263557
Dissecting the IMpact of 11-OXygenated and Classic Androgens on Skeletal Muscle Insulin Sensitivity (DIMOXIS)
A study testing Dehydroepiandrosterone (DHEA) and 11-ketoandrostenedione (11KA4) in people with Polycystic Ovary Syndrome and Insulin Resistance, run by Royal College of Surgeons, Ireland at 1 site in Ireland.
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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Polycystic Ovary Syndrome, Insulin Resistance, Androgen; Hypersecretion
- What is being tested?
- Dehydroepiandrosterone (DHEA) and 11-ketoandrostenedione (11KA4)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteIreland
- Study dates
- 19 Aug 2022to Dec 2024
- 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
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Ireland1 site, 1 recruiting
- Recruiting
Beaumont Hospital
Dublin
Michael O'Reilly, 018093894, michaelworeilly@rcsi.ie
About this study
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
Read more
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:
- Oral androgen exposure in women with PCOS results in distinct changes in tissue-specific insulin sensitivity and muscle energy biogenesis
- 11-oxygenated androgen exposure exerts differential changes on the above parameters in comparison to classic androgen exposure
The study has the following aims:
- To examine the impact of oral androgen exposure on skeletal muscle insulin sensitivity and glucose disposal in women with PCOS.
- To delineate the impact of androgen exposure on muscle mitochondrial function ex vivo in women with PCOS
- 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.
- Conditions
- Polycystic Ovary Syndrome, Insulin Resistance, Androgen; Hypersecretion, Endocrine System Diseases
- Being tested
- Dehydroepiandrosterone (DHEA), 11-ketoandrostenedione (11KA4)
- Keywords
- PCOS
- Medical subject headings
- Polycystic Ovary Syndrome, Insulin Resistance, Endocrine System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dehydroepiandrosterone (DHEA)Dietary supplement
Dehydroepiandrosterone (DHEA) at a dose of 150mg once daily for 7 days.
11-ketoandrostenedione (11KA4)Dietary supplement
11ketoandrostenedione (11KA4) at a doses of 150mg once daily for 7 days.
| Study group | Role | What they receive |
|---|---|---|
| DHEA | Experimental | Adult females with polycystic ovary syndrome (PCOS) and evidence of clinical or biochemical androgen excess will be recruited and randomised. Receives: 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. Receives: Dietary Supplement: 11-ketoandrostenedione (11KA4) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative change in glucose disposal from baseline with 11KA4 administration compared to that seen with DHEA
Utilizing hyperglycaemic-euglycaemic clamp (μmol/min/kg)
Measured: 7 Days
Secondary outcomes (2)
Relative change in glucose oxidation from baseline with 11KA4 administration compared to that seen with DHEA
Measured by 13C-breath testing (mg/kg/min)
Measured: 7 Days
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)
Measured: 7 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2022
- Study start19 Aug 2022
- Primary completionDec 2024 (estimated)
- Study completionDec 2024 (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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Interventional
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal College of Surgeons, Ireland
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford, University of Birmingham
- Responsible party
- Sponsor
- Investigators
- Michael W Michael, Principal investigator, RCSI Education & Research Centre, Beaumont Hospital, Beaumont Dublin 9 Ireland Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05263557
- Sponsor's protocol ID
- DIMOXIS
- Acronym
- DIMOXIS
- Status last verified
- Jun 2023
- First submitted
- 20 Oct 2021
- Last updated
- 25 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dissecting the IMpact of 11-OXygenated and Classic Androgens on Skeletal Muscle Insulin Sensitivity (DIMOXIS)
- ClinicalTrials.gov ID
- NCT05263557
- Acronym / sponsor ID
- DIMOXIS / DIMOXIS
- Conditions
- Polycystic Ovary Syndrome, Insulin Resistance, Androgen; Hypersecretion, Endocrine System Diseases
- Keywords
- PCOS
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Royal College of Surgeons, IrelandUniversity, hospital or other
- Collaborators
- University of Oxford, University of Birmingham
- Study start
- 19 Aug 2022 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 2 Mar 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.
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:
- Oral androgen exposure in women with PCOS results in distinct changes in tissue-specific insulin sensitivity and muscle energy biogenesis
- 11-oxygenated androgen exposure exerts differential changes on the above parameters in comparison to classic androgen exposure
The study has the following aims:
- To examine the impact of oral androgen exposure on skeletal muscle insulin sensitivity and glucose disposal in women with PCOS.
- To delineate the impact of androgen exposure on muscle mitochondrial function ex vivo in women with PCOS
- 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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Interventional
| Arm | Type | Receives |
|---|---|---|
| DHEA | Experimental | Dietary Supplement: Dehydroepiandrosterone (DHEA)Adult females with polycystic ovary syndrome (PCOS) and evidence of clinical or biochemical androgen excess will be recruited and randomised. |
| 11KA4 | Experimental | Dietary Supplement: 11-ketoandrostenedione (11KA4)Adult females with polycystic ovary syndrome (PCOS) and evidence of clinical or biochemical androgen excess will be recruited and randomised. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 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 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)
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 |
|---|---|---|
| Dehydroepiandrosterone (DHEA)Dehydroepiandrosterone (DHEA) at a dose of 150mg once daily for 7 days. | Dietary supplement | DHEA |
| 11-ketoandrostenedione (11KA4)11ketoandrostenedione (11KA4) at a doses of 150mg once daily for 7 days. | Dietary supplement | 11KA4 |
Primary outcome
Relative change in glucose disposal from baseline with 11KA4 administration compared to that seen with DHEA
Time frame: 7 Days
Utilizing hyperglycaemic-euglycaemic clamp (μmol/min/kg)
2 secondary outcomes
Relative change in glucose oxidation from baseline with 11KA4 administration compared to that seen with DHEA
Time frame: 7 Days
Relative change in endogenous glucose production from baseline with 11KA4 administration compared to that seen with DHEA (μmol/min/kg)
Time frame: 7 Days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2023.
- Individual participant dataSharing planned: No
Related trials for Polycystic Ovary Syndrome
Recruiting
Efficacy of Ovarian Drilling Via vNOTES Laparoscopy in Patients With PCOS
PCOS (Polycystic Ovary Syndrome)
RecruitingPhase 1
Efficacy of Injectable Vitamin D Supplementation in Females With Polycystic Ovary Syndrome
Anovulatory Infertility
RecruitingObservational study
The Value of LC-MS/MS Detection of Androgen Profiles in the Diagnosis of PCOS: A Prospective, Multicenter Real-world Study
Polycystic Ovary Syndrome (PCOS)
Recruiting
The Effects of the Mediterranean Diet and Synbiotics in Polycystic Ovary Syndrome
PCOS (Polycystic Ovary Syndrome)
Recruiting
Brown Adipose Tissue Modulation in Polycystic Ovary Syndrome Using Infrared Thermography
Polycystic Ovary Syndrome (PCOS)
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.
Michael W Michael principal investigator
RCSI Education & Research Centre, Beaumont Hospital, Beaumont Dublin 9 Ireland Ireland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dehydroepiandrosterone (DHEA) and 11-ketoandrostenedione (11KA4) in people with Polycystic Ovary Syndrome and Insulin Resistance, 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 4 inclusion and 12 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 25 Jul 2023. 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?
Contact Michael W O'Reilly (018093894, michaelworeilly@rcsi.ie), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative change in glucose disposal from baseline with 11KA4 administration compared to that seen with DHEA (time frame: 7 Days). 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 25 Jul 2023.