Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06544473
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-08-05
Brief Title:
Determining Dose Equivalence Between Oral and Transdermal Estrogen Treatment in Women With Turner Syndrome
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Determining Dose Equivalence Between Oral and Transdermal Estrogen Treatment in Women With Turner Syndrome - A Randomized Study
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This 5-week phase IV randomized crossover trial aims to compare the effects of oral versus transdermal estrogen replacement therapy ERT in women with Turner syndrome TS The objective is to establish the equipotency between the two estradiol regimens by evaluating various estradiol-dependent surrogate markers The study involves 50 women with TS aged 18-50 years who are randomized to receive either oral or transdermal ERT for 14 days followed by a crossover to the alternate treatment for another 14 days with a one-week washout period in between Blood tests are conducted at baseline after the first 14 days of treatment after the washout period and after the final 14 days of treatment The investigators anticipate that this study will provide clinicians with a better understanding of ERT in treating women with TS
Detailed Description:
OBJECTIVE
1 To determine the equipotency of two different estradiol regimens oral versus transdermal administration using various estradiol-dependent surrogate markers
BACKGROUND Turner syndrome TS is a rare genetic condition affecting approximately 1 in 2000 female births A hallmark of TS is ovarian dysgenesis leading to hypogonadism premature ovarian failure and infertility Consequently estrogen replacement therapy ERT is typically initiated around age 11-12 to induce puberty and continued until the average age of menopause 50-55 years aiming for at least 42 years of adequate estrogen exposure
Hypogonadism in TS is associated with various health complications Importantly estradiol E2 replacement may mitigate these risks Estrogen deficiency in TS affects cardiovascular health hypertension congenital cardiac disease altered lipid profiles metabolic function diabetes thyroid dysfunction hepatic disorders kidney disease skeletal abnormalities and is linked to neurocognitive and social challenges
E2 can be administered orally or transdermally TD but it remains unclear whether either route offers specific advantages There is ongoing debate regarding a potential increased thromboembolic risk in TS patients treated with oral E2 Epidemiological studies in postmenopausal women have reported an elevated thromboembolic risk associated with oral estrogen treatment but to a lesser extent with TD administration However extrapolating data from postmenopausal women to TS patients is inappropriate as women with TS receive estrogen as replacement therapy due to inadequate endogenous production Furthermore limited knowledge exists regarding the side effects of oral versus TD estrogen replacement therapy for TS patients
MATERIALS AND METHODS
Women aged 18-50 years with TS recruited primarily from the Department of Endocrinology at Aarhus University Hospital n50 300 patients with TS are currently followed in the outpatient clinic The investigators also have the opportunity to recruit from the Turner Association in Denmark and finally the investigators do have contact with other outpatient clinics with TS patients in Denmark from where the investigators have previously recruited TS patients
Design
A 5-week phase IV randomized crossover trial involving 50 women with TS Participants are randomized to receive E2 for 14 days either as oral or TD treatment followed by a crossover to the alternate treatment for another 14 days with a one-week washout period in between
Laboratory analyses
Blood samples are collected at baseline after the first 14 days of treatment after the washout period and after the final 14 days of treatment
STATISTICS
Data will be summarized by treatment group and assessment time point The investigators will use a mixed model with repeated measures analysis of variance ANOVA to compare the mean changes in each of the study variables between treatments over time When appropriate transformations or nonparametric methods will be used All tests are two-tailed with a 5 level of significance Data are presented as mean SE or median with CI for metrics not normally distributed
PERSPECTIVES
Patients with TS undergo hormone replacement therapy from puberty to menopause spanning more than 40 years of treatment To date only two experimental studies have compared oral and TD ERT in TS focusing solely on metabolic parameters and finding no differences between the two regimens The investigators aim for this study to provide clinicians with a better understanding of ERT in treating women with TS and to contribute with new knowledge about hormonal treatment for the general population as well
1 To determine the equipotency of two different estradiol regimens oral versus transdermal administration using various estradiol-dependent surrogate markers
BACKGROUND Turner syndrome TS is a rare genetic condition affecting approximately 1 in 2000 female births A hallmark of TS is ovarian dysgenesis leading to hypogonadism premature ovarian failure and infertility Consequently estrogen replacement therapy ERT is typically initiated around age 11-12 to induce puberty and continued until the average age of menopause 50-55 years aiming for at least 42 years of adequate estrogen exposure
Hypogonadism in TS is associated with various health complications Importantly estradiol E2 replacement may mitigate these risks Estrogen deficiency in TS affects cardiovascular health hypertension congenital cardiac disease altered lipid profiles metabolic function diabetes thyroid dysfunction hepatic disorders kidney disease skeletal abnormalities and is linked to neurocognitive and social challenges
E2 can be administered orally or transdermally TD but it remains unclear whether either route offers specific advantages There is ongoing debate regarding a potential increased thromboembolic risk in TS patients treated with oral E2 Epidemiological studies in postmenopausal women have reported an elevated thromboembolic risk associated with oral estrogen treatment but to a lesser extent with TD administration However extrapolating data from postmenopausal women to TS patients is inappropriate as women with TS receive estrogen as replacement therapy due to inadequate endogenous production Furthermore limited knowledge exists regarding the side effects of oral versus TD estrogen replacement therapy for TS patients
MATERIALS AND METHODS
Women aged 18-50 years with TS recruited primarily from the Department of Endocrinology at Aarhus University Hospital n50 300 patients with TS are currently followed in the outpatient clinic The investigators also have the opportunity to recruit from the Turner Association in Denmark and finally the investigators do have contact with other outpatient clinics with TS patients in Denmark from where the investigators have previously recruited TS patients
Design
A 5-week phase IV randomized crossover trial involving 50 women with TS Participants are randomized to receive E2 for 14 days either as oral or TD treatment followed by a crossover to the alternate treatment for another 14 days with a one-week washout period in between
Laboratory analyses
Blood samples are collected at baseline after the first 14 days of treatment after the washout period and after the final 14 days of treatment
STATISTICS
Data will be summarized by treatment group and assessment time point The investigators will use a mixed model with repeated measures analysis of variance ANOVA to compare the mean changes in each of the study variables between treatments over time When appropriate transformations or nonparametric methods will be used All tests are two-tailed with a 5 level of significance Data are presented as mean SE or median with CI for metrics not normally distributed
PERSPECTIVES
Patients with TS undergo hormone replacement therapy from puberty to menopause spanning more than 40 years of treatment To date only two experimental studies have compared oral and TD ERT in TS focusing solely on metabolic parameters and finding no differences between the two regimens The investigators aim for this study to provide clinicians with a better understanding of ERT in treating women with TS and to contribute with new knowledge about hormonal treatment for the general population as well
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None