Ignite Creation Date:
2024-05-06 @ 8:08 PM
Last Modification Date:
2024-10-26 @ 3:21 PM
Study NCT ID:
NCT06264882
Status:
RECRUITING
Last Update Posted:
2024-06-20
First Post:
2024-02-07
Brief Title:
Cardiometabolic Consequences of the Loss of Ovarian Function
Sponsor:
University of Colorado Denver
Organization:
University of Colorado Denver
Study Overview
Official Title:
Cardiometabolic Consequences of the Loss of Ovarian Function
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
LILAC
Brief 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 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 eg 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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U54AG062319 | NIH | None | httpsreporternihgovquickSearchU54AG062319 |