MenopausePhase 1NCT06704516
COmmencing Menopausal HOrmone Replacement Therapy and the Effect on Metabolic-dysfunction Associated Steatotic Liver Disease: a Pilot Mechanistic Study
A Phase 1 study testing Menopausal hormone therapy in people with Menopause and Metabolic Dysfunction Associated Steatotic Liver Disease, run by University of Oxford at 1 site in United Kingdom.
Trial summary
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease worldwide, currently affecting approximately 1-in-4 people globally. The prevalence is expected to rise further, driven at least partly by the epidemic of obesity and diabetes. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Menopause, Metabolic Dysfunction Associated Steatotic Liver Disease
- What is being tested?
- Menopausal hormone therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2025to 1 Jan 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Potential participant is willing and able to give informed consent for participation in the trial
- In the Investigator's opinion, is able and willing to comply with all trial requirements
- Female, aged 18 years and above
- Body mass index 18 to 45 kg/m2
- Postmenopausal status:
- For women ≥ 40 defined clinically (amenorrhoea for ≥ 1 year) or biochemically (FSH >30IU/L on 2 occasions 4-6 weeks apart).
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- For women < 40 defined as a combination of oligomenorrhoea/amenorrhoea for ≥ 4 months and FSH >30IU/L on 2 occasions 4-6 weeks apart
- Women who have undergone bilateral oophorectomy (no additional testing is required)
- Low oestradiol levels
- No exposure to systemic oestrogen-based HRT within the previous 3 months
- Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the trial.
Who cannot join
- Potential participant with known chronic liver disease, with the exception of MASLD
- The use of drugs which, in the opinion of the investigator, will significantly impact on hepatic lipid content or metabolism. This applies to drugs currently being used or used in the past, within a timeframe where the investigator believes it may impact hepatic lipid content or metabolism.
- Potential participant with any other medical explanation for amenorrhoea, apart from menopause
- History of harmful alcohol consumption (>35 units/week) or alcohol misuse disorder
- Potential participants with contraindication to MRI
- Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
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- Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
- Potential participant with life expectancy of less than 6 months.
- Potential participants who have participated in another research trial involving an investigational product in the past 12 weeks.
- Potential participants without a sufficient understanding of written or verbal English to participate in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Oxford Centre for Diabetes Endocrinology and Metabolism (OCDEM), Churchill Hospital
Oxford, Oxfordshire, OX3 7LE
Jiawen Dong, MB BChir, MRCP, +441865 857300, jiawen.dong@ocdem.ox.ac.uk
Jeremy Tomlinson, MB BCh, PhD, FRCP
About this study
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease worldwide, currently affecting approximately 1-in-4 people globally. The prevalence is expected to rise further, driven at least partly by the epidemic of obesity and diabetes. MASLD is a condition of fat build-up in the liver that can progress to liver scarring which is associated with higher chances of death. Women are more than twice as likely to develop MASLD after menopause compared to before menopause, and previous research has shown that this may be caused by a lack of oestrogen. A lack of oestrogen is also believed to lead to harmful changes in adipose (body fat), which has an important role in the development of MASLD. Oestrogen contained in hormone replacement therapy (HRT) is an effective treatment for hot flushes and other problems in menopause. The popularity of HRT has increased dramatically in the United Kingdom in recent years, however the exact way in which it affects adipose and MASLD is unclear. The investigators will study how HRT affects the processes that drive MASLD in 10 women before and after using the treatment. This is a small-scale pilot study to understand feasibility of recruitment and test the procedures for a future, larger-scale studies.
The investigators will recruit women who are about to begin HRT for the first time and perform the same tests for each participant before starting HRT, and after using HRT for 12-weeks. The participants will undergo meal testing including non-radioactive, stable isotopes, and blood and breath samples will be collected to measure fat processing. The total fat content of the liver will be measured using magnetic resonance imaging (MRI) scans. Adipose samples will be collected, fat metabolites will be measured and the distribution of fat around the body will be assessed using a dual energy x-ray absorptiometry (DEXA) scan. To find out how HRT affects these processes, the results from before and after using HRT will be compared. Understanding how HRT affects adipose and the liver may help reduce the development of MASLD in women after the menopause and improve their health and survival.
- Being tested
- Menopausal hormone therapy
- Keywords
- hormone, MASLD, NAFLD, liver, estrogen, replacement, adipose, oestrogen, fat, MASH, steatosis
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Platelet Glycoprotein IV Deficiency, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Menopausal hormone therapyDrug
Any brand, composition, route and dose of systemic menopausal hormone therapy containing oestrogen.
Brands of HRT include oestrogel, Evorel, Lenzetto, Estradot, Progynova (this list is not exhaustive)
| Study group | Role | What they receive |
|---|---|---|
| Hormone Replacement Therapy | Experimental | Participants starting any brand, composition, route and dose of oestrogen-based systemic hormone replacement therapy, will be included in this group. Receives: Drug: Menopausal hormone therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment into an experimental medicine study investigating the impact of HRT on MASLD
Number of participants who are screened and recruited into the study
Measured: 7 months
Secondary outcomes (10)
Acceptability of experimental protocols in experimental medicine study investigating the impact of HRT on MASLD
Feedback from questionnaire completed by study participants
Measured: From enrollment to the end of the study after completing 12 weeks of intervention
Participant retention in an experimental medicine study investigating the impact of HRT on MASLD
Number of participants who complete the study (per protocol)
Measured: From enrollment to the end of the study after completing 12 weeks of intervention
Fatty acid esterification into triglyceride
Measurement of 13C-palmitate incorporation into very low density lipoprotein triglyceride (VLDL-TG)
Measured: Performed at baseline and after 12 weeks of intervention
Hepatic lipid content
Measurement of intrahepatic triglyceride content by magnetic resonance imaging / spectroscopy
Measured: At baseline and after 12 weeks of intervention
Whole body fatty acid oxidation
Measurement of incorporation of 13C into breath CO2 using GC-C-IRMS.
Measured: At baseline and after 12 weeks of intervention
Fasting and postprandial plasma intrahepatic fatty acid synthesis.
Change in hepatic fatty acid synthesis as measured by incorporation of 2H2 palmitate (via 2H2O) into VLDL-TG
Measured: At baseline and after 12 weeks of intervention
Liver profile blood tests and circulating lipid profiles
Routine laboratory biochemistry
Measured: At baseline and after 12 weeks of intervention
Interstitial levels of metabolites in adipose tissue
Change in adipose tissue metabolite profile
Measured: At baseline and after 12 weeks of intervention
Adipose tissue transcriptomic profile
Change in adipose tissue transcriptomic profile in abdominal subcutaneous and gluteal depots
Measured: At baseline and after 12 weeks of intervention
Total and regional lean and fat tissue distribution
Total and regional lean and fat mass on Dual energy X-ray absorptiometry (DXA) scan
Measured: At baseline and after 12 weeks of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2024
- Study startJan 2025 (estimated)
- Primary completion5 Aug 2025 (estimated)
- Study completion1 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MenopauseStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Oxford University Hospitals NHS Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06704516
- Sponsor's protocol ID
- 345429
- Status last verified
- Jan 2025
- First submitted
- 29 Oct 2024
- Last updated
- 13 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COmmencing Menopausal HOrmone Replacement Therapy and the Effect on Metabolic-dysfunction Associated Steatotic Liver Disease: a Pilot Mechanistic Study
- ClinicalTrials.gov ID
- NCT06704516
- Acronym / sponsor ID
- 345429
- Keywords
- hormone, MASLD, NAFLD, liver, estrogen, replacement, adipose, oestrogen
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Oxford University Hospitals NHS Trust
- Study start
- Jan 2025 (estimated)
- Primary completion
- 5 Aug 2025 (estimated)
- Study completion
- 1 Jan 2026 (estimated)
- First posted
- 26 Nov 2024 (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.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease worldwide, currently affecting approximately 1-in-4 people globally. The prevalence is expected to rise further, driven at least partly by the epidemic of obesity and diabetes. MASLD is a condition of fat build-up in the liver that can progress to liver scarring which is associated with higher chances of death. Women are more than twice as likely to develop MASLD after menopause compared to before menopause, and previous research has shown that this may be caused by a lack of oestrogen. A lack of oestrogen is also believed to lead to harmful changes in adipose (body fat), which has an important role in the development of MASLD. Oestrogen contained in hormone replacement therapy (HRT) is an effective treatment for hot flushes and other problems in menopause. The popularity of HRT has increased dramatically in the United Kingdom in recent years, however the exact way in which it affects adipose and MASLD is unclear. The investigators will study how HRT affects the processes that drive MASLD in 10 women before and after using the treatment. This is a small-scale pilot study to understand feasibility of recruitment and test the procedures for a future, larger-scale studies.
The investigators will recruit women who are about to begin HRT for the first time and perform the same tests for each participant before starting HRT, and after using HRT for 12-weeks. The participants will undergo meal testing including non-radioactive, stable isotopes, and blood and breath samples will be collected to measure fat processing. The total fat content of the liver will be measured using magnetic resonance imaging (MRI) scans. Adipose samples will be collected, fat metabolites will be measured and the distribution of fat around the body will be assessed using a dual energy x-ray absorptiometry (DEXA) scan. To find out how HRT affects these processes, the results from before and after using HRT will be compared. Understanding how HRT affects adipose and the liver may help reduce the development of MASLD in women after the menopause and improve their health and survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hormone Replacement Therapy | Experimental | Drug: Menopausal hormone therapyParticipants starting any brand, composition, route and dose of oestrogen-based systemic hormone replacement therapy, will be included in this group. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Potential participant is willing and able to give informed consent for participation in the trial
- In the Investigator's opinion, is able and willing to comply with all trial requirements
- Female, aged 18 years and above
- Body mass index 18 to 45 kg/m2
- Postmenopausal status:
Key exclusion criteria (10 listed)
- Potential participant with known chronic liver disease, with the exception of MASLD
- The use of drugs which, in the opinion of the investigator, will significantly impact on hepatic lipid content or metabolism. This applies to drugs currently being used or used in the past, within a timeframe where the investigator believes it may impact hepatic lipid content or metabolism.
- Potential participant with any other medical explanation for amenorrhoea, apart from menopause
- History of harmful alcohol consumption (>35 units/week) or alcohol misuse disorder
- Potential participants with contraindication to MRI
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 |
|---|---|---|
| Menopausal hormone therapyAny brand, composition, route and dose of systemic menopausal hormone therapy containing oestrogen. Brands of HRT include oestrogel, Evorel, Lenzetto, Estradot, Progynova (this list is not exhaustive) | Drug | Hormone Replacement Therapy |
Primary outcome
Recruitment into an experimental medicine study investigating the impact of HRT on MASLD
Time frame: 7 months
Number of participants who are screened and recruited into the study
10 secondary outcomes
Acceptability of experimental protocols in experimental medicine study investigating the impact of HRT on MASLD
Time frame: From enrollment to the end of the study after completing 12 weeks of intervention
Participant retention in an experimental medicine study investigating the impact of HRT on MASLD
Time frame: From enrollment to the end of the study after completing 12 weeks of intervention
Fatty acid esterification into triglyceride
Time frame: Performed at baseline and after 12 weeks of intervention
Hepatic lipid content
Time frame: At baseline and after 12 weeks of intervention
Whole body fatty acid oxidation
Time frame: At baseline and after 12 weeks of intervention
Fasting and postprandial plasma intrahepatic fatty acid synthesis.
Time frame: At baseline and after 12 weeks of intervention
Liver profile blood tests and circulating lipid profiles
Time frame: At baseline and after 12 weeks of intervention
Interstitial levels of metabolites in adipose tissue
Time frame: At baseline and after 12 weeks of intervention
Adipose tissue transcriptomic profile
Time frame: At baseline and after 12 weeks of intervention
Total and regional lean and fat tissue distribution
Time frame: At baseline and after 12 weeks of intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2025.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Menopausal hormone therapy in people with Menopause and Metabolic Dysfunction Associated Steatotic Liver Disease, run by University of Oxford at 1 site in United Kingdom.
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 11 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 13 Jan 2025. 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 United Kingdom. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jiawen Dong, MB BChir, MRCP (+441865 857300, jiawen.dong@ocdem.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment into an experimental medicine study investigating the impact of HRT on MASLD (time frame: 7 months). 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 13 Jan 2025.