Ignite Creation Date:
2024-10-26 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 3:38 PM
Study NCT ID:
NCT06570460
Status:
RECRUITING
Last Update Posted:
None
First Post:
2019-12-04
Brief Title:
Long Term Effects of Oral Versus Transdermal Estrogen Replacement Therapy in Turner Syndrome
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Long Term Effects of Oral Versus Transdermal Estrogen Replacement Therapy in Turner Syndrome - A Randomized Trial
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 14-month phase IV randomized controlled crossover trial aims to compare the effects of oral versus transdermal estrogen replacement therapy ERT in women with Turner syndrome TS The studys objectives are to clarify endocrine metabolic cardiovascular and thromboembolic risk factors in TS after a wash-out period without estrogen E2 treatment compare the effects of oral versus transdermal TD ERT regimens and examine the long-term effects of E2 administration via these two routes The study involves 50 TS women aged 18-50 years and 50 control participants TS participants are randomized to receive either oral or TD ERT for six months followed by crossover to the alternate treatment for another six months Prior to randomization any existing ERT will be discontinued for a 1-month washout period A second 1-month washout period will occur between the two 6-month treatment phases Laboratory analyses and clinical investigations are performed after the first wash-out period after the first six months of treatment and after the last six months of treatment We anticipate that this study may provide a basis for new and improved recommendations for sex hormone replacement therapy in TS
Detailed Description:
OBJECTIVES
1 Clarify endocrine metabolic cardiovascular and thromboembolic risk factors in Turner syndrome TS after a wash out period
2 Compare the effects of oral versus transdermal TD estrogen replacement therapy ERT in women with Turner syndrome
3 Examine long term effects of ERT via the two routes on endocrine metabolic cardiovascular physiologic and thromboembolic risk endpoints
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
Study group
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
An age-matched control group of healthy women is included by advertisement n50
Inclusion criteria
For participants with TS
Diagnosis of TS regardless of karyotype
Age 18-50 years
Already receiving estrogen treatment
For healthy controls
Female
Age 18-50 years
Previously healthy
Not receiving any medication
Not using any form of contraceptive pills
No mental or psychiatric disorders
Exclusion criteria
Active systemic chronic diseases
Known or suspected breast cancer
Known or suspected estradiol-dependent tumors endometrial cancer or similar
Untreated endometrial hyperplasia
Current or previous venous thromboembolism
Acute or previous liver disease where liver enzymes are still elevated by a factor 3 or more
Known hypersensitivity to the medications used
Pregnancy
Menopause for the control group only
Design
A 14-month phase IV randomized controlled crossover study involving women with Turner Syndrome TS n50 and healthy age-matched controls n50 TS participants are randomized to receive either oral or TD ERT for six months followed by crossover to the alternate treatment for another six months Prior to randomization any existing ERT will be discontinued for a 1-month washout period A second 1-month washout period will occur between the two 6-month treatment phases Healthy controls will not receive any treatment They will undergo a single set of assessments for comparison
Laboratory analyses and clinical investigations will be conducted at the Department of Endocrinology and the associated Medical Research Unit at Aarhus University Hospital These will include blood and urine sample collection as well as specific clinical investigations At baseline both TS patients and healthy controls will undergo these assessments Only TS patients will undergo follow-up assesments
Clinical investigations
Insulin sensitivity assessment
24-hour blood pressure monitoring
DEXA scan Dual-Energy X-ray Absorptiometry
Bioelectrical impedance analysis Multiplate
Comprehensive clinical examination
Quality of life assessments using questionnaires
SphygmoCor analysis
VO2 max test using a stationary bike
MRI of the thigh muscles to measure muscle cross-sectional area CSA and intramuscular fat content
Isometric muscle strength testing and functional testing
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 If the investigators hypotheses are correct and if the side effects including increased thromboembolic risk are higher with oral than TD ERT this project could be crucial for optimizing treatment improving quality of life and reducing morbidity and mortality in TS The investigators aim for this study to provide a basis for new and improved national and international recommendations for ERT in TS patients and to contribute new knowledge about hormonal treatment for the general population as well
1 Clarify endocrine metabolic cardiovascular and thromboembolic risk factors in Turner syndrome TS after a wash out period
2 Compare the effects of oral versus transdermal TD estrogen replacement therapy ERT in women with Turner syndrome
3 Examine long term effects of ERT via the two routes on endocrine metabolic cardiovascular physiologic and thromboembolic risk endpoints
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
Study group
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
An age-matched control group of healthy women is included by advertisement n50
Inclusion criteria
For participants with TS
Diagnosis of TS regardless of karyotype
Age 18-50 years
Already receiving estrogen treatment
For healthy controls
Female
Age 18-50 years
Previously healthy
Not receiving any medication
Not using any form of contraceptive pills
No mental or psychiatric disorders
Exclusion criteria
Active systemic chronic diseases
Known or suspected breast cancer
Known or suspected estradiol-dependent tumors endometrial cancer or similar
Untreated endometrial hyperplasia
Current or previous venous thromboembolism
Acute or previous liver disease where liver enzymes are still elevated by a factor 3 or more
Known hypersensitivity to the medications used
Pregnancy
Menopause for the control group only
Design
A 14-month phase IV randomized controlled crossover study involving women with Turner Syndrome TS n50 and healthy age-matched controls n50 TS participants are randomized to receive either oral or TD ERT for six months followed by crossover to the alternate treatment for another six months Prior to randomization any existing ERT will be discontinued for a 1-month washout period A second 1-month washout period will occur between the two 6-month treatment phases Healthy controls will not receive any treatment They will undergo a single set of assessments for comparison
Laboratory analyses and clinical investigations will be conducted at the Department of Endocrinology and the associated Medical Research Unit at Aarhus University Hospital These will include blood and urine sample collection as well as specific clinical investigations At baseline both TS patients and healthy controls will undergo these assessments Only TS patients will undergo follow-up assesments
Clinical investigations
Insulin sensitivity assessment
24-hour blood pressure monitoring
DEXA scan Dual-Energy X-ray Absorptiometry
Bioelectrical impedance analysis Multiplate
Comprehensive clinical examination
Quality of life assessments using questionnaires
SphygmoCor analysis
VO2 max test using a stationary bike
MRI of the thigh muscles to measure muscle cross-sectional area CSA and intramuscular fat content
Isometric muscle strength testing and functional testing
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 If the investigators hypotheses are correct and if the side effects including increased thromboembolic risk are higher with oral than TD ERT this project could be crucial for optimizing treatment improving quality of life and reducing morbidity and mortality in TS The investigators aim for this study to provide a basis for new and improved national and international recommendations for ERT in TS patients and to contribute 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