Ignite Creation Date:
2024-05-05 @ 10:40 PM
Last Modification Date:
2024-10-26 @ 10:22 AM
Study NCT ID:
NCT01161823
Status:
UNKNOWN
Last Update Posted:
2016-01-12
First Post:
2010-04-16
Brief Title:
Influence of Nebivolol on Postmenopausal Women
Sponsor:
Medical University of Vienna
Organization:
Medical University of Vienna
Study Overview
Official Title:
Effect of Nebivolol on Climacteric Disorders in Postmenopausal Women A Randomized Open Label Trial
Status:
UNKNOWN
Status Verified Date:
2010-04
Last Known Status:
RECRUITING
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:
None
Brief Summary:
After menopause the coronary artery disease CAD risk increases rapidly to an equivalent risk of men with the same age The rising incidence of CAD could be a subsequent decline of endogenous estrogen blood levels after the menopause Estrogen leads to vasodilation and vasoprotection through an increase of Nitric Oxide NO NO deficiency results in endothelial stiffness and dysfunction with a subsequent initiation of atherosclerosis Menopausal status is associated with an increase of the sympathetic nerve activity leading to hypertension increased heart rate and palpitations Recent studies show an importance of vasoactive substances eg NO in the physiology of hot flashes Thus hot flashes may be associated with a decreased NO production and release Additionally it is well known that during and after menopause women experience a change in sexual function declined libido and increased dyspareunia due to decreasing estrogen blood levels Recently a new angiostatic parameter - Endostatin ENST - has been shown to be involved in EC function There is also evidence that ENST levels increase during NO stimulation Nebivolol a ß-blocker of the third generation has been shown to release NO to a significant amount in the EC It is safe and effective in reducing blood pressure to the target level However there is no data of the effect of Nebivolol on sexual function on clinical symptoms palpitations increased heart rate and hot flashes and ENST in postmenopausal women The present study investigates the effect of a NO-releasing ß-blocker compared to a phytoestrogen therapy considering clinical signs of menopause such as palpitations hot flashes and sexual functioning in postmenopausal women Therefore the use of a ß-blocker treatment is warranted Further this study tries to elucidate the role of NO release in postmenopausal symptoms and may gain new insights in the pathophysiology of hot flashes and increased sympathetic nerve activity Thus this trial should explore an advantage of Nebivolol therapy in contrast to a phytoestrogen therapy
Null hypothesis Climacteric disorders as measured by the MRS-II in patients with a Nebivolol therapy is not lower than in patients with phytoestrogen therapy Alternative hypothesis Climacteric disorders in patients as measured by the MRS-II with a Nebivolol therapy is lower than in patients with phytoestrogen therapy
Null hypothesis Climacteric disorders as measured by the MRS-II in patients with a Nebivolol therapy is not lower than in patients with phytoestrogen therapy Alternative hypothesis Climacteric disorders in patients as measured by the MRS-II with a Nebivolol therapy is lower than in patients with phytoestrogen therapy
Detailed Description:
1 Background
CAD is the leading cause of mortality for women in US as well as in Austria and most developed countries
Major risk factors are hypertension diabetes and the postmenopausal status After the menopause the CAD risk increases rapidly to an equivalent risk of men with the same age
In all ethnic groups hypertension is more prevalent among women than men after the age of 59 Over 75 years 752 of females and 637 of males perform a hypertensive vascular status
Menopausal status is associated with a decline of endogenous estrogen levels resulting in a manifest estrogen deficiency This estrogen decline is also associated with a subsequent increased risk for CAD
The main effect of estrogen is a vasodilatation and an anti-atherosclerotic action through different mechanisms
Recent studies are describing that the estrogen deficiency and the subsequently NO deficiency results in a disordered endothelial function and a permanent vasoconstriction that is one of the major reasons for postmenopausal hypertension and CAD
Clinical symptoms of postmenopausal women
- Palpitations and tachycardia Postmenopausal women complain about heart palpitations throbbing and subjective sensed high heart rate and tachycardia which can be explained by a sympathetic over activity in postmenopausal women
This clinical symptoms are associated with a significant decrease in quality of life and well- being in postmenopausal women
- Hot flashes Hot flashes are the most common symptom and occur in most postmenopausal women 75 Hot flashes are experienced as a feeling of intense heat with sweating and rapid heartbeat The typical duration is between two and thirty minutes Risk factors for hot flashes are - equal to CVD - high body mass index and smoking
Furthermore it can be supposed that the NO decrease in postmenopausal women is responsible for the hot flashes
- Sexuality Sexuality is an important quality-of-life issue also in elderly Therefore sexual dysfunction is considered a serious quality-of-life-related health problem Furthermore increasing dyspareunia and decreasing libido and responsivity correlated with decreasing estrogen levels
- Endostatin ENST ENST a 20-kDa C-terminal fragment cleaved from type XVIII collagen is a naturally occurring protein that blocks the formation of blood vessels inhibits EC proliferation migration and angiogenesis Furthermore there is evidence that ENST induces an acute NO release and finally leads to vasodilation and therefore works against endothelial dysfunction
However since there is no data on ENST serum levels in postmenopausal women as well of the effect of Nebivolol on ENST serum levels we will investigate baseline ENST levels and after 3 month of treatment compared to patients treated with phytohormones
- Nebivolol Nebivolol a ß-blocker of the third generation has been shown to lower blood pressure with great safety and efficacy in men as well in women and was well tolerated
Beneath its specific beta-1-receptor blockade Nebivolol has a NO-releasing effect through a ß3-receptor-agonism Nebivolol combines a potent ß1-adrenoreceptor-blocking activity mostly ascribed to its D-enantiomer with additional vasodilating properties attributed to its L-enantiomer and also D-enantiomer
Nebivolol causes a vasodilatation of the vessels and reduces the progress of atherosclerosis which is a main risk factor for CVD and hypertension
The current general guidelines for hypertension recommend treatment with a Thiazide Diuretic as a first line medication in hypertension In contrary to Diuretics and ACE-blockers - ß-blockers also reduce the heart rate and have positive antagonistic influence on the sympathetic nerve system The augmentation of the heart rate during the menopause is sensed as a very unpleasant and unbearable situation for most of the postmenopausal women Thus the increase in sympathetic nerve activity and clinical symptoms of palpitations or increased heart rate warrant the use of a ß-blocker for the treatment in our cohort
Additionally we hypothesise that through an improvement of the endothelial function with Nebivolol the number of hot flashes in postmenopausal women can be reduced
Recent studies have shown positive effects on the erectile dysfunction in men during treatment with Nebivolol As the physiologic and embryologic conditions are almost similar in men and women so we expect similar improving effects on the sexual dysfunction in our female study group
Therefore we want to investigate the effect of Nebivolol on blood pressure heart rate hot flashes sexual function ENST testosterone levels in postmenopausal women with menopausal disorders
12 Rationale of the study
We want to investigate the effect of Nebivolol in comparison to a phytoestrogen therapy on climacteric disorders as measured by the Menopausal rating scale II MRS-II In addition we will investigate the following
- the heart rate
- the number of palpitations
- the number of hot flushes
- the sexual function
- the blood pressure
- the serum level of Endostatin
the serum level of Testosterone in postmenopausal women
2 METHODS 21 Measurement of the blood pressure Measurement of the blood pressure according to Riva Rocci will be performed at the beginning and after 12 weeks end of the study Measurements will be taken in sitting position after five minutes rest Three consecutive measurements will be taken and the average of these measurements will be recorded
22 ECG A 12-lead ECG will be written to rule out AV-block and bradycardia 50min
23 Blood parameters
Prestudy screening
- FSH
- TSH
- testosterone
- estrogen
- DHEA
SHBG
prolactin
BNP
hsCRP
liver parameters
kidney parameters
electrolytes
blood glucose
Our patients have to show a blood level of estrogen 20pgml and FSH 35 mIUml to verify the status of menopause
To rule out another endocrine cause of a possible sexual function alteration we check the blood levels of TSH Prolactin DHEA Dehydroepiandrosterone and SHBG Sex Hormon Binding Globulin
24 Analysis of Endostatin Within the routine blood analysis we will also detect the blood level of ENST
The RD191076100 Human Endostatin ELISA is a sandwich enzyme immunoassay for the quantitative measurement of endostatin protein in human serum
25 Female Sexual Function Index We will use the German version of the female sexual function index FSFI-D that was validated in 2004 This questionnaire is a proven instrument to evaluate the female sexual function especially in postmenopausal women
We will hand out this questionnaire twice At the beginning and after our study 12 weeks later During the completion of the questionnaire by the study participant a gynecologist will be attendant to help the women to complete the questionnaire
This way we want to analyze if the treatment with Nebivolol has an effect on the sexual function of women We have added the questionnaire to the appendix
26 Menopausal Rating Scale II We are going to use the Menopause Rating Scale II MRS II This self-assessment scale to quantify menopausal symptoms includes 11 questions to evaluate the quality of life in our cohort
We will hand out this questionnaire twice At the beginning and after our study 12 weeks later During the completion of the questionnaire by the study participant a gynecologist will be attendant to help the women to complete the questionnaire
27 Hot flashespalpitations diary At the beginning of our study the diary will be introduced to the patients by the treating physician There the number of hot flashes and palpitations per day should be written down The diary contains 12 pages one page a week
At the beginning we will perform an anamnesis to get informed about the average number of hot flashes and palpitations per day before the medication
CAD is the leading cause of mortality for women in US as well as in Austria and most developed countries
Major risk factors are hypertension diabetes and the postmenopausal status After the menopause the CAD risk increases rapidly to an equivalent risk of men with the same age
In all ethnic groups hypertension is more prevalent among women than men after the age of 59 Over 75 years 752 of females and 637 of males perform a hypertensive vascular status
Menopausal status is associated with a decline of endogenous estrogen levels resulting in a manifest estrogen deficiency This estrogen decline is also associated with a subsequent increased risk for CAD
The main effect of estrogen is a vasodilatation and an anti-atherosclerotic action through different mechanisms
Recent studies are describing that the estrogen deficiency and the subsequently NO deficiency results in a disordered endothelial function and a permanent vasoconstriction that is one of the major reasons for postmenopausal hypertension and CAD
Clinical symptoms of postmenopausal women
- Palpitations and tachycardia Postmenopausal women complain about heart palpitations throbbing and subjective sensed high heart rate and tachycardia which can be explained by a sympathetic over activity in postmenopausal women
This clinical symptoms are associated with a significant decrease in quality of life and well- being in postmenopausal women
- Hot flashes Hot flashes are the most common symptom and occur in most postmenopausal women 75 Hot flashes are experienced as a feeling of intense heat with sweating and rapid heartbeat The typical duration is between two and thirty minutes Risk factors for hot flashes are - equal to CVD - high body mass index and smoking
Furthermore it can be supposed that the NO decrease in postmenopausal women is responsible for the hot flashes
- Sexuality Sexuality is an important quality-of-life issue also in elderly Therefore sexual dysfunction is considered a serious quality-of-life-related health problem Furthermore increasing dyspareunia and decreasing libido and responsivity correlated with decreasing estrogen levels
- Endostatin ENST ENST a 20-kDa C-terminal fragment cleaved from type XVIII collagen is a naturally occurring protein that blocks the formation of blood vessels inhibits EC proliferation migration and angiogenesis Furthermore there is evidence that ENST induces an acute NO release and finally leads to vasodilation and therefore works against endothelial dysfunction
However since there is no data on ENST serum levels in postmenopausal women as well of the effect of Nebivolol on ENST serum levels we will investigate baseline ENST levels and after 3 month of treatment compared to patients treated with phytohormones
- Nebivolol Nebivolol a ß-blocker of the third generation has been shown to lower blood pressure with great safety and efficacy in men as well in women and was well tolerated
Beneath its specific beta-1-receptor blockade Nebivolol has a NO-releasing effect through a ß3-receptor-agonism Nebivolol combines a potent ß1-adrenoreceptor-blocking activity mostly ascribed to its D-enantiomer with additional vasodilating properties attributed to its L-enantiomer and also D-enantiomer
Nebivolol causes a vasodilatation of the vessels and reduces the progress of atherosclerosis which is a main risk factor for CVD and hypertension
The current general guidelines for hypertension recommend treatment with a Thiazide Diuretic as a first line medication in hypertension In contrary to Diuretics and ACE-blockers - ß-blockers also reduce the heart rate and have positive antagonistic influence on the sympathetic nerve system The augmentation of the heart rate during the menopause is sensed as a very unpleasant and unbearable situation for most of the postmenopausal women Thus the increase in sympathetic nerve activity and clinical symptoms of palpitations or increased heart rate warrant the use of a ß-blocker for the treatment in our cohort
Additionally we hypothesise that through an improvement of the endothelial function with Nebivolol the number of hot flashes in postmenopausal women can be reduced
Recent studies have shown positive effects on the erectile dysfunction in men during treatment with Nebivolol As the physiologic and embryologic conditions are almost similar in men and women so we expect similar improving effects on the sexual dysfunction in our female study group
Therefore we want to investigate the effect of Nebivolol on blood pressure heart rate hot flashes sexual function ENST testosterone levels in postmenopausal women with menopausal disorders
12 Rationale of the study
We want to investigate the effect of Nebivolol in comparison to a phytoestrogen therapy on climacteric disorders as measured by the Menopausal rating scale II MRS-II In addition we will investigate the following
- the heart rate
- the number of palpitations
- the number of hot flushes
- the sexual function
- the blood pressure
- the serum level of Endostatin
the serum level of Testosterone in postmenopausal women
2 METHODS 21 Measurement of the blood pressure Measurement of the blood pressure according to Riva Rocci will be performed at the beginning and after 12 weeks end of the study Measurements will be taken in sitting position after five minutes rest Three consecutive measurements will be taken and the average of these measurements will be recorded
22 ECG A 12-lead ECG will be written to rule out AV-block and bradycardia 50min
23 Blood parameters
Prestudy screening
- FSH
- TSH
- testosterone
- estrogen
- DHEA
SHBG
prolactin
BNP
hsCRP
liver parameters
kidney parameters
electrolytes
blood glucose
Our patients have to show a blood level of estrogen 20pgml and FSH 35 mIUml to verify the status of menopause
To rule out another endocrine cause of a possible sexual function alteration we check the blood levels of TSH Prolactin DHEA Dehydroepiandrosterone and SHBG Sex Hormon Binding Globulin
24 Analysis of Endostatin Within the routine blood analysis we will also detect the blood level of ENST
The RD191076100 Human Endostatin ELISA is a sandwich enzyme immunoassay for the quantitative measurement of endostatin protein in human serum
25 Female Sexual Function Index We will use the German version of the female sexual function index FSFI-D that was validated in 2004 This questionnaire is a proven instrument to evaluate the female sexual function especially in postmenopausal women
We will hand out this questionnaire twice At the beginning and after our study 12 weeks later During the completion of the questionnaire by the study participant a gynecologist will be attendant to help the women to complete the questionnaire
This way we want to analyze if the treatment with Nebivolol has an effect on the sexual function of women We have added the questionnaire to the appendix
26 Menopausal Rating Scale II We are going to use the Menopause Rating Scale II MRS II This self-assessment scale to quantify menopausal symptoms includes 11 questions to evaluate the quality of life in our cohort
We will hand out this questionnaire twice At the beginning and after our study 12 weeks later During the completion of the questionnaire by the study participant a gynecologist will be attendant to help the women to complete the questionnaire
27 Hot flashespalpitations diary At the beginning of our study the diary will be introduced to the patients by the treating physician There the number of hot flashes and palpitations per day should be written down The diary contains 12 pages one page a week
At the beginning we will perform an anamnesis to get informed about the average number of hot flashes and palpitations per day before the medication
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2009-011527-31 | EUDRACT_NUMBER | None | None |