MenopausePhase 4LILACNCT06264882
Cardiometabolic Consequences of the Loss of Ovarian Function
A Phase 4 study testing Degarelix and Transdermal Estradiol Patch in people with Menopause and Estrogen Deficiency, run by University of Colorado, Denver at 1 site in United States.
Trial summary
The menopause transition is associated with a decrease in artery health and an increased risk for weight gain in storing fat in the stomach area which may increase the risk for heart disease. Read more about this study
- Who is it for?
- Ages 20 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Menopause, Estrogen Deficiency, Aging
- What is being tested?
- Degarelix and Transdermal Estradiol Patch
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2024to 31 Aug 2028
- Phase
- Phase 4
- 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 20 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age criteria of 20-45 years: the investigators are determining the effects of ovarian suppression on adiposity and vascular in premenopausal women;
- Premenopausal defined as normal menstrual cycle function defined as no more than 1 missed cycle in the previous year: irregular menstrual or missed menstrual cycles could indicate that women are anovulatory and/or perimenopause;
- Not pregnant or planning to become pregnant;
- Not lactating in the last 3 months;
- Serum FSH <10 IU/L measured during days 1-10 of the menstrual cycle: to ensure the woman is premenopausal and not perimenopausal;
- Not on hormonal contraception in the last 3 months;
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- Sedentary or recreationally active (<2 days/wk vigorous exercise);
- No use of medications that might influence vascular function (i.e., antihypertensives, lipid lowering medications, blood thinners);
- No use of antioxidant supplements or chronic NSAIDs or be willing to go off them for 4 weeks prior to enrollment in the study;
Who cannot join
- Diabetic or fasted glucose >126 mg/dL;
- Body mass index (BMI) >35 kg/m2;
- Weight change >5 kg in the last 3 months;
- Use of glucocorticoids (inhaled, oral, topical) or drugs that affect glucocorticoid metabolism (e.g., ketoconazole) in the last 3 months;
- Excess alcohol consumption, defined as >14 drinks per week by self-report;
- Known hypersensitivity to study medications;
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- Depressive symptoms, defined as a CES-D score >16;
- Resting blood pressure >150/90 mmHg;
- Preexisting or active cardiac, renal, or hepatic disease: past or current history of these diseases or conditions;
- Active or chronic infection: inflammation associated with active or chronic infections impair vascular function;
- Thyroid dysfunction, defined as an ultrasensitive TSH <0.5 or >5.0 mU/L; volunteers with abnormal TSH values will be reconsidered for participation in the study after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement;
- Smoking or Tobacco use within the previous 12 months;
- Severe low bone mass or osteoporosis, defined as a hip or lumbar spine T-score <-2.0: safety reasons, women who are randomized to the ovarian suppression plus placebo group could see a decrease in bone mineral density due to the suppression of estrogen;
- History of venous thromboembolic event (VTE): safety reasons, estradiol therapy can increase the risk of VTE;
- History of breast cancer or other estrogen-dependent neoplasm: estradiol therapy is contraindicated;
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
Kerrie L Moreau, PhD, 303-724-1914, kerrie.moreau@ucdenver.edu
About this study
The menopause transition is associated with a decrease in artery health and an increased risk for weight gain in storing fat in the stomach area which may increase the risk for heart disease. The purpose of this research is to study how the decrease in estrogen at menopause changes artery health and fat gain, and risk of disease in women as they age. The first aim in this study will determine whether short term and long term low estrogen levels in premenopausal women decreases artery function and whether this is related to an increase in fat in the stomach area. The second aim will determine whether the changes in artery health and body fat are related to changes in a pathway that breaks down an important amino acid called tryptophan. This pathway is thought to play a role in regulating the aging process. Therefore, the investigators will determine whether the decrease in artery health and the increase in body fat in the stomach region with low estrogen is related to changes in this pathway in the blood, in vascular cells and fat tissue. Because estrogen levels fluctuate in premenopausal women, the investigators will use an approach (intervention) that controls estrogen levels to address these aims. The investigators will use a medication that is typically used to treat endometriosis or uterine fibroids to lower estrogen levels and an estrogen patch to increase estrogen in some women. Some women will receive a patch that has no estrogen (called a placebo patch). The intervention period will be 20 weeks. The study will provide us with new knowledge on how low estrogen with menopause affects artery health and fat gain estrogen.
Read the detailed description
Menopause accelerates cardiovascular disease (CVD) risk due to adverse changes in risk factors (e.g., increased body fat) and vascular health, related to changes in the hormone environment. The investigators showed that measures of vascular health progressively worsen across the menopause transition, related to increased oxidative stress. The oxidative stress-mediated vascular dysfunction was related to the loss of estrogen. The loss of estrogen with menopause also causes an increase in percent body fat levels, particularly in the abdominal region. However, it is unknown if the increase in abdominal body fat worsens vascular dysfunction with the loss of estrogen. Thus Aim 1 of Project 1 will investigate the impact of increased abdominal adiposity superimposed on the direct effects of estrogen deficiency on vascular function in women. In collaboration with SCORE Projects 2 and 3, Aim 2 and an Exploratory aim will investigate the underlying causes for the increase in abdominal body fat and vascular dysfunction. There is emerging evidence that links the tryptophan-kynurenine (TRP-KYN) pathway as a regulator of vascular function, body fat and the aging process. TRP is an essential amino acid that is metabolized to KYN and various metabolites. KYN and some of its breakdown products have been associated with an increase in body fat and an impairment in vascular function. It is unknown if estrogen regulates this pathway. Thus, Aim 2 and the Exploratory aim will investigate if the TRP-KYN pathway is dysregulated with the loss of estrogen, and if this is associated with an increase in abdominal body fat and an impairment in endothelial function.
The Aims of Project 1 will be accomplished by conducting an intervention trial in premenopausal women randomized to a low estrogen condition (gonadotropin releasing hormone antagonist, GnRHant, plus a placebo patch) or a high estrogen condition (GnRHant plus an estrogen patch) to isolate the actions of estrogen. Women will wear a patch daily that will be switched out weekly. At weeks 9 and 17, women will receive 5 mg of medroxyprogesterone acetate (MPA) for 12 days to prevent endometrial hyperplasia. Outcomes will be assessed before the intervention and after 2 and 20 weeks of the intervention, except where indicated. All women will continue their intervention until testing has been completed. Initially, women interested in the study will undergo a phone or e-mail screening to assess likelihood for eligibility.
- Conditions
- Menopause, Estrogen Deficiency, Aging, Adiposity
- Being tested
- Degarelix, Transdermal Estradiol Patch, Transdermal Placebo Patch
- Keywords
- Vascular biology, Women's health, Women
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DegarelixDrug
Also called GnRH antagonist, Ovarian suppression
After first undergoing a pregnancy test, a clinician will administer an 80-mg subcutaneous injection of degarelix acetate (20 mg/mL; Ferring Pharmaceuticals Inc, Parsippany, NJ) to the women. A second injection will occur at 10 weeks. Compliance to the intervention will be ensured by having participants receive injections in the Clinical and Translational Research Center (CTRC), where all study visits will take place.
Transdermal Estradiol PatchDrug
Treatment will be a weekly transdermal patch (0.075 mg) administered in a double-blinded manner. This estradiol dose increases serum estradiol to ~90 pg/mL. Compliance to the intervention will be monitored by having participants keep a log that tracks patch use.
Transdermal Placebo PatchDrug
Treatment will be a weekly transdermal patch (placebo inactive) administered in a double-blinded manner. Compliance to the intervention will be monitored by having participants keep a log that tracks patch use.
| Study group | Role | What they receive |
|---|---|---|
| Degarelix plus transdermal placebo | Experimental | At baseline \& 10 weeks: 80-mg subcutaneous injection of degarelix acetate plus Placebo transdermal patch (applied twice per week) Receives: Drug: Degarelix; Drug: Transdermal Placebo Patch |
| Degarelix plus transdermal estradiol | Experimental | At baseline \& 10 weeks: 80-mg subcutaneous injection of degarelix acetate plus 0.075mg estradiol transdermal patch (applied twice per week) Receives: Drug: Degarelix; Drug: Transdermal Estradiol Patch |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brachial artery flow mediated dilation (FMD)
Ultrasound measurements of brachial artery FMD will be performed in the morning under fasted conditions, and analyzed (Vascular Analysis Tools 5.5.1) according to guidelines. Baseline FMD will be assessed during early follicular phase of menstrual cycle. Blood pressure will be measured prior to the FMD. To confirm endothelial-specific effects of the intervention, the investigators will also measure endothelium-independent dilation as brachial artery dilation to sublingual nitroglycerine (0.4 mg). All ultrasound images will be coded by number and blinded to group assignment.
Measured: Baseline and at 2 and 20 weeks
Secondary outcomes (1)
Visceral fat area (VFA)
Participants will undergo a CT scan of the abdomen for the assessment of VFA and subcutaneous fat area (SFA). Axial CT images will be obtained through the center of the L2-L3 inter-vertebral disc space at 120 kVp (kilovoltage peak), 200-300 maS, and 10mm slice thickness. Digital images will be analyzed in a blinded manner by the University of Colorado Research Imaging Center (CU-RIC) using Interactive Data language software (ITT Visualization Solutions, Boulder, CO).
Measured: Baseline and at 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2024
- Study start1 Jun 2024
- Primary completion31 May 2028 (estimated)
- Study completion31 Aug 2028 (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 Colorado, DenverThe 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Kerrie Moreau, PhD, Principal investigator, University of Colorado Denver Anschutz Medical Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06264882
- Sponsor's protocol ID
- 23-1518
- Other IDs
- U54AG062319
- Acronym
- LILAC
- Status last verified
- Jun 2024
- First submitted
- 7 Feb 2024
- Last updated
- 20 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- 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 20 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiometabolic Consequences of the Loss of Ovarian Function
- ClinicalTrials.gov ID
- NCT06264882
- Acronym / sponsor ID
- LILAC / 23-1518
- Conditions
- Menopause, Estrogen Deficiency, Aging, Adiposity
- Keywords
- Vascular biology, Women's health, Women
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 31 May 2028 (estimated)
- Study completion
- 31 Aug 2028 (estimated)
- First posted
- 20 Feb 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.
The menopause transition is associated with a decrease in artery health and an increased risk for weight gain in storing fat in the stomach area which may increase the risk for heart disease. The purpose of this research is to study how the decrease in estrogen at menopause changes artery health and fat gain, and risk of disease in women as they age. The first aim in this study will determine whether short term and long term low estrogen levels in premenopausal women decreases artery function and whether this is related to an increase in fat in the stomach area. The second aim will determine whether the changes in artery health and body fat are related to changes in a pathway that breaks down an important amino acid called tryptophan. This pathway is thought to play a role in regulating the aging process. Therefore, the investigators will determine whether the decrease in artery health and the increase in body fat in the stomach region with low estrogen is related to changes in this pathway in the blood, in vascular cells and fat tissue. Because estrogen levels fluctuate in premenopausal women, the investigators will use an approach (intervention) that controls estrogen levels to address these aims. The investigators will use a medication that is typically used to treat endometriosis or uterine fibroids to lower estrogen levels and an estrogen patch to increase estrogen in some women. Some women will receive a patch that has no estrogen (called a placebo patch). The intervention period will be 20 weeks. The study will provide us with new knowledge on how low estrogen with menopause affects artery health and fat gain estrogen.
Detailed description
Menopause accelerates cardiovascular disease (CVD) risk due to adverse changes in risk factors (e.g., increased body fat) and vascular health, related to changes in the hormone environment. The investigators showed that measures of vascular health progressively worsen across the menopause transition, related to increased oxidative stress. The oxidative stress-mediated vascular dysfunction was related to the loss of estrogen. The loss of estrogen with menopause also causes an increase in percent body fat levels, particularly in the abdominal region. However, it is unknown if the increase in abdominal body fat worsens vascular dysfunction with the loss of estrogen. Thus Aim 1 of Project 1 will investigate the impact of increased abdominal adiposity superimposed on the direct effects of estrogen deficiency on vascular function in women. In collaboration with SCORE Projects 2 and 3, Aim 2 and an Exploratory aim will investigate the underlying causes for the increase in abdominal body fat and vascular dysfunction. There is emerging evidence that links the tryptophan-kynurenine (TRP-KYN) pathway as a regulator of vascular function, body fat and the aging process. TRP is an essential amino acid that is metabolized to KYN and various metabolites. KYN and some of its breakdown products have been associated with an increase in body fat and an impairment in vascular function. It is unknown if estrogen regulates this pathway. Thus, Aim 2 and the Exploratory aim will investigate if the TRP-KYN pathway is dysregulated with the loss of estrogen, and if this is associated with an increase in abdominal body fat and an impairment in endothelial function.
The Aims of Project 1 will be accomplished by conducting an intervention trial in premenopausal women randomized to a low estrogen condition (gonadotropin releasing hormone antagonist, GnRHant, plus a placebo patch) or a high estrogen condition (GnRHant plus an estrogen patch) to isolate the actions of estrogen. Women will wear a patch daily that will be switched out weekly. At weeks 9 and 17, women will receive 5 mg of medroxyprogesterone acetate (MPA) for 12 days to prevent endometrial hyperplasia. Outcomes will be assessed before the intervention and after 2 and 20 weeks of the intervention, except where indicated. All women will continue their intervention until testing has been completed. Initially, women interested in the study will undergo a phone or e-mail screening to assess likelihood for eligibility.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Degarelix plus transdermal placebo | Experimental | Drug: Degarelix, Drug: Transdermal Placebo PatchAt baseline \& 10 weeks: 80-mg subcutaneous injection of degarelix acetate plus Placebo transdermal patch (applied twice per week) |
| Degarelix plus transdermal estradiol | Experimental | Drug: Degarelix, Drug: Transdermal Estradiol PatchAt baseline \& 10 weeks: 80-mg subcutaneous injection of degarelix acetate plus 0.075mg estradiol transdermal patch (applied twice per week) |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Age criteria of 20-45 years: the investigators are determining the effects of ovarian suppression on adiposity and vascular in premenopausal women;
- Premenopausal defined as normal menstrual cycle function defined as no more than 1 missed cycle in the previous year: irregular menstrual or missed menstrual cycles could indicate that women are anovulatory and/or perimenopause;
- Not pregnant or planning to become pregnant;
- Not lactating in the last 3 months;
- Serum FSH <10 IU/L measured during days 1-10 of the menstrual cycle: to ensure the woman is premenopausal and not perimenopausal;
Key exclusion criteria (15 listed)
- Diabetic or fasted glucose >126 mg/dL;
- Body mass index (BMI) >35 kg/m2;
- Weight change >5 kg in the last 3 months;
- Use of glucocorticoids (inhaled, oral, topical) or drugs that affect glucocorticoid metabolism (e.g., ketoconazole) in the last 3 months;
- Excess alcohol consumption, defined as >14 drinks per week by self-report;
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 |
|---|---|---|
| DegarelixAlso: GnRH antagonist, Ovarian suppressionAfter first undergoing a pregnancy test, a clinician will administer an 80-mg subcutaneous injection of degarelix acetate (20 mg/mL; Ferring Pharmaceuticals Inc, Parsippany, NJ) to the women. A second injection will occur at 10 weeks. Compliance to the intervention will be ensured by having participants receive injections in the Clinical and Translational Research Center (CTRC), where all study visits will take place. | Drug | Degarelix plus transdermal estradiol, Degarelix plus transdermal placebo |
| Transdermal Estradiol PatchTreatment will be a weekly transdermal patch (0.075 mg) administered in a double-blinded manner. This estradiol dose increases serum estradiol to ~90 pg/mL. Compliance to the intervention will be monitored by having participants keep a log that tracks patch use. | Drug | Degarelix plus transdermal estradiol |
| Transdermal Placebo PatchTreatment will be a weekly transdermal patch (placebo inactive) administered in a double-blinded manner. Compliance to the intervention will be monitored by having participants keep a log that tracks patch use. | Drug | Degarelix plus transdermal placebo |
Primary outcome
Brachial artery flow mediated dilation (FMD)
Time frame: Baseline and at 2 and 20 weeks
Ultrasound measurements of brachial artery FMD will be performed in the morning under fasted conditions, and analyzed (Vascular Analysis Tools 5.5.1) according to guidelines. Baseline FMD will be assessed during early follicular phase of menstrual cycle. Blood pressure will be measured prior to the FMD. To confirm endothelial-specific effects of the intervention, the investigators will also measure endothelium-independent dilation as brachial artery dilation to sublingual nitroglycerine (0.4 mg). All ultrasound images will be coded by number and blinded to group assignment.
1 secondary outcome
Visceral fat area (VFA)
Time frame: Baseline and at 20 weeks
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 20 Jun 2024.
- 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.
Kerrie Moreau, PhD principal investigator
University of Colorado Denver Anschutz Medical Campus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Degarelix and Transdermal Estradiol Patch in people with Menopause and Estrogen Deficiency, run by University of Colorado, Denver at 1 site in United States.
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 9 inclusion and 15 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 20 Jun 2024. 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 States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Kerrie Moreau, PhD (303-724-1914, kerrie.moreau@cuanschutz.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brachial artery flow mediated dilation (FMD) (time frame: Baseline and at 2 and 20 weeks). 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 20 Jun 2024.