Heart DiseasesPhase 4NCT04671966
Sex Differences in Myocardial Steatosis Induced Left Ventricular Dysfunction
A Phase 4 study testing Estradiol patch, Cetrotide and Fasting in people with Heart Diseases and Left Ventricular Dysfunction, run by The University of Texas at Arlington at 1 site in United States.
Trial summary
To test the specific research questions, healthy men and age-matched healthy premenopausal females will be enrolled. Subjects will undergo cardiac magnetic resonance imaging and spectroscopy (MRI/MRS) to evaluate cardiac morphology/function and fat metabolism. Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Diseases, Left Ventricular Dysfunction
- What is being tested?
- Estradiol patch, Cetrotide and Fasting
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Sep 2018to Dec 2024
- Phase
- Phase 4
- 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 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- blood pressure <140/90 mmHg
- BMI between 18.5 and 30 kg/m2
- sedentary or recreationally active (<3 days of vigorous aerobic exercise each week)
- no use of oral contraceptives hormone therapy, or other medications that might influence cardiovascular function
- nonsmokers.
Who cannot join
- Women will be excluded with
- history of or active estrogen-dependent neoplasms, acute liver or gallbladder disease, vaginal bleeding, venous thromboembolism, hypertriglyceridemia, and CVD
- known allergy to transdermal patch, GnRHant (i.e., hypersensitivity to cetrorelix, extrinsic peptide hormones, mannitol, GnRH, benzyl alcohol - the vehicle for injection of cetrorelix)
- history of stomach ulcer or bleeding
- other contraindications to hormone replacement therapy or GnRHant, (i.e., taking Levodopa, medications that can inhibit folate metabolism including methotrexate).
- Other conditions for which individuals will be excluded from the study include:
- diabetes active infection history of seizures or disease that affects the nervous system sepsis an abnormal resting ECG contraindications to MRI pregnant or planning to become pregnant smoking history illicit drug use (excluding occasional marijuana).
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University of Texas at Arlington
Arlington, Texas, 76019
manall jaffery, MS, 469-426-4030, manall.jaffery@uta.edu
michael nelson, PhD, 8175130383, michael.nelson3@uta.edu
About this study
Official title: Mechanism and Modulation of Sex Differences in Myocardial Steatosis Induced Left Ventricular Dysfunction
To test the specific research questions, healthy men and age-matched healthy premenopausal females will be enrolled. Subjects will undergo cardiac magnetic resonance imaging and spectroscopy (MRI/MRS) to evaluate cardiac morphology/function and fat metabolism. To acutely elevate myocardial triglyceride content, subjects will be asked to abstain from eating for 2 days (reproducibly causes a significant and physiological increase in myocardial fat deposition, transiently). Subjects will be allowed water and/or an isotonic saline solution in order to maintain hydration status. After screening, subjects will meet with the research coordinator or an investigator for a discussion, with opportunity for questions, before applicable consent forms are obtained. The subject will be screened for metal in or on their body and claustrophobia using a standard MR screening form. A venous blood sample will be taken for measurement of metabolic health, circulating hormones, and systemic inflammation. Imaging will include cine imaging for global morphology and function, tissue tagging for regional tissue deformation, spectroscopy for fat quantification. After baseline images of the heart are obtained, the subject will be asked to squeeze a MR-safe handgrip dynamometer at 30% of their maximum while images of the heart are obtained. Blood pressure will also be measured at rest and during stress. Each MRI will take approximately 90-120 minutes.
Aim 1 will test the hypothesis that cardiac steatosis induced left ventricular dysfunction is sexually dimorphic, by comparing age-matched men and premenopausal women before and after 48 of fasting. Subjects will complete the MRI/MRS protocol described above before and after the fasting intervention.
Read more
Aim 2 will test the hypothesis that estrogen is protective against cardiac steatosis-induced dysfunction, by suppressing ovarian sex hormones with a GnRH antagonist and repeating the fasting studies with and without estrogen add-back. 30 female subjects will be treated with GnRH antagonist and repeat the 48 hour fasting intervention and cardiac MRI/MRS protocol. 15 of the subjects will receive estrogen add-back using a transdermal patch, the other 15 subjects will receive a placebo patch.
Aim 3 will test whether plasma and myocardial fatty acid composition is sexually dimorphic, by performing comprehensive plasma and myocardial lipidomics assessment.
- Conditions
- Heart Diseases, Left Ventricular Dysfunction
- Being tested
- Estradiol patch, Cetrotide, Fasting, Lower Body Negative Pressure
- Keywords
- myocardial steatosis, fasting, estrogen, biological sex as a variable
- Medical subject headings
- Heart Diseases, Ventricular Dysfunction, Left, Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol patchDrug
Brand name Climara for estrogen add back portion of study. Premenopausal women treated with a GnRH antagonist will be randomized to estrogen add-back or placebo. Thus, for women without contradictions to estrogen use, the risks associated with their use for the duration proposed in these studies (i.e., 6 days) are small. The respective estradiol regimen is a standard approved dose for treatment of hot flashes and the prevention of osteoporosis, and this dose will increase E2 to concentrations typically observed during the mid to late follicular phase of the menstrual cycle.
CetrotideDrug
Premenopausal women will be treated with the gonadotropin-releasing hormone (GnRH) antagonist Cetrorelix for 6 days in order to suppress ovarian sex hormones. Cetrorelix may cause an anaphylactic reaction in volunteers with hypersensitivity to cetrorelix, GnRH or any other GnRH analogs, or extrinsic peptide hormones or mannitol. It may also cause hot flashes, headaches, and nausea. These are typically transient and of mild intensity. These effects are all reversible upon cessation of cetrorelix. Absence of pregnancy will be confirmed before drug administration.
FastingOther
Subjects will abstain from food for 48 hours. Subjects will be allowed water and/or an isotonic saline solution in order to maintain hydration status.
Lower Body Negative PressureOther
Also called LBNP
This test simulates Earth's gravity. The subject will rest on his/her back, with their lower body sealed in an air-tight chamber from the waist down. The chamber is connected to a vacuum that sucks air from the chamber and creates negative pressure inside and around the subject's lower body. As a result, the subject's blood pool shifts towards their legs, away from their chest and arms.
| Study group | Role | What they receive |
|---|---|---|
| Fasting only | Experimental | To acutely elevate myocardial triglyceride content, subjects will be asked to abstain from eating for 2 days (reproducibly causes a significant and physiological increase in myocardial fat deposition, transiently). Subjects will be allowed water and/or an isotonic saline solution in order to maintain hydration status. Receives: Other: Fasting |
| LBNP Only | Experimental | Subjects undergo lower body negative pressure at 40 mmHg. Receives: Other: Lower Body Negative Pressure |
| Estrogen add back with GnRHant | Experimental | Subjects are given estradiol patch. Receives: Drug: Estradiol patch; Drug: Cetrotide; Other: Fasting |
| Placebo add back with GnRHant | Experimental | Subjects are given placebo patch. Receives: Drug: Cetrotide; Other: Fasting |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in left ventricular relaxation rate
Measured at each of the 4 MRIs by tissue tagging
Measured: 1 week
Comprehensive plasma lipidomics
Measured from blood drawn at each of the 4 MRIs
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2020
- Study start13 Sep 2018
- 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 Heart DiseasesStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Subjects are studied (bloods and MRI) before and after intervention (2 day fast or 2 day fast with GnRH antagonist and estrogen add back).
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Texas at Arlington
- Sponsor type
- University, hospital or other
- Collaborators
- University of Texas Southwestern Medical Center
- Responsible party
- Sponsor
- Investigators
- michael nelson, PhD, Principal investigator, University of Texas at Arlington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04671966
- Sponsor's protocol ID
- STU 112017-013
- Status last verified
- Feb 2024
- First submitted
- 3 Dec 2020
- Last updated
- 20 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanism and Modulation of Sex Differences in Myocardial Steatosis Induced Left Ventricular Dysfunction
- ClinicalTrials.gov ID
- NCT04671966
- Acronym / sponsor ID
- STU 112017-013
- Conditions
- Heart Diseases, Left Ventricular Dysfunction
- Keywords
- myocardial steatosis, fasting, estrogen, biological sex as a variable
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- The University of Texas at ArlingtonUniversity, hospital or other
- Collaborators
- University of Texas Southwestern Medical Center
- Study start
- 13 Sep 2018 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 17 Dec 2020 (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.
To test the specific research questions, healthy men and age-matched healthy premenopausal females will be enrolled. Subjects will undergo cardiac magnetic resonance imaging and spectroscopy (MRI/MRS) to evaluate cardiac morphology/function and fat metabolism. To acutely elevate myocardial triglyceride content, subjects will be asked to abstain from eating for 2 days (reproducibly causes a significant and physiological increase in myocardial fat deposition, transiently). Subjects will be allowed water and/or an isotonic saline solution in order to maintain hydration status. After screening, subjects will meet with the research coordinator or an investigator for a discussion, with opportunity for questions, before applicable consent forms are obtained. The subject will be screened for metal in or on their body and claustrophobia using a standard MR screening form. A venous blood sample will be taken for measurement of metabolic health, circulating hormones, and systemic inflammation. Imaging will include cine imaging for global morphology and function, tissue tagging for regional tissue deformation, spectroscopy for fat quantification. After baseline images of the heart are obtained, the subject will be asked to squeeze a MR-safe handgrip dynamometer at 30% of their maximum while images of the heart are obtained. Blood pressure will also be measured at rest and during stress. Each MRI will take approximately 90-120 minutes.
Aim 1 will test the hypothesis that cardiac steatosis induced left ventricular dysfunction is sexually dimorphic, by comparing age-matched men and premenopausal women before and after 48 of fasting. Subjects will complete the MRI/MRS protocol described above before and after the fasting intervention.
Aim 2 will test the hypothesis that estrogen is protective against cardiac steatosis-induced dysfunction, by suppressing ovarian sex hormones with a GnRH antagonist and repeating the fasting studies with and without estrogen add-back. 30 female subjects will be treated with GnRH antagonist and repeat the 48 hour fasting intervention and cardiac MRI/MRS protocol. 15 of the subjects will receive estrogen add-back using a transdermal patch, the other 15 subjects will receive a placebo patch.
Aim 3 will test whether plasma and myocardial fatty acid composition is sexually dimorphic, by performing comprehensive plasma and myocardial lipidomics assessment.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Subjects are studied (bloods and MRI) before and after intervention (2 day fast or 2 day fast with GnRH antagonist and estrogen add back).
| Arm | Type | Receives |
|---|---|---|
| Fasting only | Experimental | Other: FastingTo acutely elevate myocardial triglyceride content, subjects will be asked to abstain from eating for 2 days (reproducibly causes a significant and physiological increase in myocardial fat deposition, transiently). Subjects will be allowed water and/or an isotonic saline solution in order to maintain hydration status. |
| LBNP Only | Experimental | Other: Lower Body Negative PressureSubjects undergo lower body negative pressure at 40 mmHg. |
| Estrogen add back with GnRHant | Experimental | Drug: Estradiol patch, Drug: Cetrotide, Other: FastingSubjects are given estradiol patch. |
| Placebo add back with GnRHant | Experimental | Drug: Cetrotide, Other: FastingSubjects are given placebo patch. |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- blood pressure <140/90 mmHg
- BMI between 18.5 and 30 kg/m2
- sedentary or recreationally active (<3 days of vigorous aerobic exercise each week)
- no use of oral contraceptives hormone therapy, or other medications that might influence cardiovascular function
- nonsmokers.
Key exclusion criteria (7 listed)
- Women will be excluded with
- diabetes active infection history of seizures or disease that affects the nervous system sepsis an abnormal resting ECG contraindications to MRI pregnant or planning to become pregnant smoking history illicit drug use (excluding occasional marijuana).
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 |
|---|---|---|
| Estradiol patchBrand name Climara for estrogen add back portion of study. Premenopausal women treated with a GnRH antagonist will be randomized to estrogen add-back or placebo. Thus, for women without contradictions to estrogen use, the risks associated with their use for the duration proposed in these studies (i.e., 6 days) are small. The respective estradiol regimen is a standard approved dose for treatment of hot flashes and the prevention of osteoporosis, and this dose will increase E2 to concentrations typically observed during the mid to late follicular phase of the menstrual cycle. | Drug | Estrogen add back with GnRHant |
| CetrotidePremenopausal women will be treated with the gonadotropin-releasing hormone (GnRH) antagonist Cetrorelix for 6 days in order to suppress ovarian sex hormones. Cetrorelix may cause an anaphylactic reaction in volunteers with hypersensitivity to cetrorelix, GnRH or any other GnRH analogs, or extrinsic peptide hormones or mannitol. It may also cause hot flashes, headaches, and nausea. These are typically transient and of mild intensity. These effects are all reversible upon cessation of cetrorelix. Absence of pregnancy will be confirmed before drug administration. | Drug | Estrogen add back with GnRHant, Placebo add back with GnRHant |
| FastingSubjects will abstain from food for 48 hours. Subjects will be allowed water and/or an isotonic saline solution in order to maintain hydration status. | Other | Estrogen add back with GnRHant, Fasting only, Placebo add back with GnRHant |
| Lower Body Negative PressureAlso: LBNPThis test simulates Earth's gravity. The subject will rest on his/her back, with their lower body sealed in an air-tight chamber from the waist down. The chamber is connected to a vacuum that sucks air from the chamber and creates negative pressure inside and around the subject's lower body. As a result, the subject's blood pool shifts towards their legs, away from their chest and arms. | Other | LBNP Only |
Primary outcome
Change in left ventricular relaxation rate
Time frame: 1 week
Measured at each of the 4 MRIs by tissue tagging
Comprehensive plasma lipidomics
Time frame: 1 week
Measured from blood drawn at each of the 4 MRIs
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2024.
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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. This study is not recruiting at the moment.
michael nelson, PhD principal investigator
University of Texas at Arlington
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 Estradiol patch, Cetrotide and Fasting in people with Heart Diseases and Left Ventricular Dysfunction, run by The University of Texas at Arlington 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 5 inclusion and 7 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 20 Feb 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact manall jaffery, MS (14694264030, manalljaffery@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in left ventricular relaxation rate (time frame: 1 week). The study lists 2 primary outcomes in all. 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 Feb 2024.