Ignite Creation Date:
2024-05-05 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00136032
Status:
COMPLETED
Last Update Posted:
2008-02-18
First Post:
2005-08-24
Brief Title:
Growth Hormone Administration and Its Effects on Cardiovascular Risk Factors in Growth Hormone Deficient Women
Sponsor:
Massachusetts General Hospital
Organization:
Massachusetts General Hospital
Study Overview
Official Title:
Gender-Specific Effects of Physiologic GH Administration on Cardiovascular Risk Factors in Women With Growth Hormone Deficiency
Status:
COMPLETED
Status Verified Date:
2008-02
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:
None
Brief Summary:
The purpose of the study is to evaluate the effects of growth hormone replacement on women with growth hormone deficiency Growth hormone deficiency means the body no longer produces growth hormone due to a tumor or some kind of disease of the brain in an area called the pituitaryhypothalamic region This is the area of the brain where growth hormone is normally produced We the researchers at Massachusetts General Hospital will establish the effects of growth hormone replacement on cardiovascular parameters laboratory tests the flexibility of the arteries changes in heart rate in women with growth hormone deficiency Our goal is to see if this therapy
has effects on womens cardiovascular risk markers special blood tests which indicate how healthy the heart and arteries are
has effects on womens types and levels of various substances circulating in their blood
in women affects the stiffness of their arteries and heart rate variability in parallel with changes in cardiovascular risk markers
has different effects depending on whether women are pre or post menopausal
Participation in this study is expected to last approximately 12 months
has effects on womens cardiovascular risk markers special blood tests which indicate how healthy the heart and arteries are
has effects on womens types and levels of various substances circulating in their blood
in women affects the stiffness of their arteries and heart rate variability in parallel with changes in cardiovascular risk markers
has different effects depending on whether women are pre or post menopausal
Participation in this study is expected to last approximately 12 months
Detailed Description:
The aim of the study is to evaluate the gender specific effects of physiologic Growth Hormone GH replacement in women with GH deficiency on the basis of pituitaryhypothalamic region tumors radiation or surgery on cardiovascular risk markers and arterial distensibility Cardiovascular mortality in growth hormone GH deficient adults has been shown to be increased in a number of retrospective studies Increased arterial intima-media thickness increased prevalence of atherosclerotic plaques and endothelial dysfunction have been reported in growth hormone deficient adults both in childhood and adulthood onset forms
The growth hormone deficiency GHD syndrome is associated with a cluster of cardiovascular-risk factors such as central adiposity increased visceral fat insulin resistance dyslipoproteinemia and decreased plasma fibrinolytic activity GH administration has effects on a number of these factors but it is unknown which mechanisms are implicated in GH action on the process of atherosclerosis In addition to alterations in atherosclerotic markers abnormalities in cardiac function and structure have been reported among patients with GHD possibly contributing to the increased cardiovascular mortality In addition GHD is associated with cardiac autonomic dysfunction that may also contribute to cardiovascular mortality and improves with GH replacement therapy
The vast majority of studies have focused primarily on men and the gender-specific effects of GH replacement on cardiovascular risk factors remain unknown In addition to being of interest in terms of understanding the physiologic effects of GH therapy there are important therapeutic implications regarding data in women Cardiovascular disease is the leading cause of mortality in women Effects of GH replacement on bone density may be less pronounced in women and because specific GH effects on cardiovascular risk factors in women are unknown many adult women with GHD are untreated
Long-term GH treatment decreases total body fat including visceral fat Decreases in central fat as assessed by waist to hip ratio have been reported in some studies but not in others Administration of GH causes insulin resistance acutely but long-term therapy may restore glucose sensitivity GH treatment increases lipoprotein a Lp a levels but its effects on other lipoproteins are still controversial Some studies have reported decreases in LDL cholesterol with or without increases in HDL cholesterol with GH administration while others have not Twelve months of GH replacement improves left ventricular mass and cardiac performance in young adults with GHD Key factors likely involved in the discrepant findings include heterogeneity of patients studied in terms of age of onset of the GH deficiency childhood versus adulthood gender severity of GHD and methodologic issues such as dose and duration of GH administration In addition many of the studies have no control period
Inflammation plays a central role in the pathophysiology of atherosclerosis Each atherosclerotic lesion represents a different stage of a chronic inflammatory process in the arterial wall and different markers along the inflammatory cascade have been reported to predict cardiovascular risk 34 Among those high-sensitivity testing for C-reactive protein CRP is one of the best validated Several prospective studies support a strong link between levels of CRP and future risk of coronary events CRP adds considerable value to the total and HDL cholesterol measurement in the prediction of cardiovascular risk Other distal indicators of inflammation such as serum-amyloid polypeptide A SAA likewise predict coronary risk These distal markers reflect the consequences of elevated proinflammatory cytokines like interleukin-6 IL-6 GH is known to have important immunomodulatory effects We therefore hypothesized that the effects of GH on the process of atherosclerosis might be mediated through the cytokine-inflammatory pathway We have recently investigated the effects of physiologic GH replacement in cardiovascular risk markers in men with GHD In this study we found that CRP and IL-6 levels decreased in GH treated men compared to controls despite no significant change in serum lipid levels We also recently have investigated levels of inflammatory markers in women with hypopituitarism compared with healthy controls We found that women with hypopituitarism have increased levels of IL-6 and CRP suggesting that chronic inflammation may be involved in the pathogenesis of atherosclerosis in this population It will be critical to determine whether physiologic GH replacement has beneficial effects in women and whether these effects are influenced by estrogen
We will investigate the effect of long-term physiologic GH administration on IL-6 CRP SAA as well as other classic cardiovascular risk factors in women with GHD in a randomized placebo-controlled study In addition we will evaluate structuralfunction correlates in women by measuring arterial wall distensibility and heart rate variability in parallel with cardiovascular risk markers
We will establish the gender-specific effects of physiologic GH replacement on cardiovascular risk in women with GHD by investigating whether this therapy
1 has gender-specific effects on cardiovascular risk markers
2 has gender-specific effects on lipid profiles
3 alters heart rate variability and arterial distensibility in parallel with changes in cardiovascular risk markers
4 has different effects depending upon gonadal status
The growth hormone deficiency GHD syndrome is associated with a cluster of cardiovascular-risk factors such as central adiposity increased visceral fat insulin resistance dyslipoproteinemia and decreased plasma fibrinolytic activity GH administration has effects on a number of these factors but it is unknown which mechanisms are implicated in GH action on the process of atherosclerosis In addition to alterations in atherosclerotic markers abnormalities in cardiac function and structure have been reported among patients with GHD possibly contributing to the increased cardiovascular mortality In addition GHD is associated with cardiac autonomic dysfunction that may also contribute to cardiovascular mortality and improves with GH replacement therapy
The vast majority of studies have focused primarily on men and the gender-specific effects of GH replacement on cardiovascular risk factors remain unknown In addition to being of interest in terms of understanding the physiologic effects of GH therapy there are important therapeutic implications regarding data in women Cardiovascular disease is the leading cause of mortality in women Effects of GH replacement on bone density may be less pronounced in women and because specific GH effects on cardiovascular risk factors in women are unknown many adult women with GHD are untreated
Long-term GH treatment decreases total body fat including visceral fat Decreases in central fat as assessed by waist to hip ratio have been reported in some studies but not in others Administration of GH causes insulin resistance acutely but long-term therapy may restore glucose sensitivity GH treatment increases lipoprotein a Lp a levels but its effects on other lipoproteins are still controversial Some studies have reported decreases in LDL cholesterol with or without increases in HDL cholesterol with GH administration while others have not Twelve months of GH replacement improves left ventricular mass and cardiac performance in young adults with GHD Key factors likely involved in the discrepant findings include heterogeneity of patients studied in terms of age of onset of the GH deficiency childhood versus adulthood gender severity of GHD and methodologic issues such as dose and duration of GH administration In addition many of the studies have no control period
Inflammation plays a central role in the pathophysiology of atherosclerosis Each atherosclerotic lesion represents a different stage of a chronic inflammatory process in the arterial wall and different markers along the inflammatory cascade have been reported to predict cardiovascular risk 34 Among those high-sensitivity testing for C-reactive protein CRP is one of the best validated Several prospective studies support a strong link between levels of CRP and future risk of coronary events CRP adds considerable value to the total and HDL cholesterol measurement in the prediction of cardiovascular risk Other distal indicators of inflammation such as serum-amyloid polypeptide A SAA likewise predict coronary risk These distal markers reflect the consequences of elevated proinflammatory cytokines like interleukin-6 IL-6 GH is known to have important immunomodulatory effects We therefore hypothesized that the effects of GH on the process of atherosclerosis might be mediated through the cytokine-inflammatory pathway We have recently investigated the effects of physiologic GH replacement in cardiovascular risk markers in men with GHD In this study we found that CRP and IL-6 levels decreased in GH treated men compared to controls despite no significant change in serum lipid levels We also recently have investigated levels of inflammatory markers in women with hypopituitarism compared with healthy controls We found that women with hypopituitarism have increased levels of IL-6 and CRP suggesting that chronic inflammation may be involved in the pathogenesis of atherosclerosis in this population It will be critical to determine whether physiologic GH replacement has beneficial effects in women and whether these effects are influenced by estrogen
We will investigate the effect of long-term physiologic GH administration on IL-6 CRP SAA as well as other classic cardiovascular risk factors in women with GHD in a randomized placebo-controlled study In addition we will evaluate structuralfunction correlates in women by measuring arterial wall distensibility and heart rate variability in parallel with cardiovascular risk markers
We will establish the gender-specific effects of physiologic GH replacement on cardiovascular risk in women with GHD by investigating whether this therapy
1 has gender-specific effects on cardiovascular risk markers
2 has gender-specific effects on lipid profiles
3 alters heart rate variability and arterial distensibility in parallel with changes in cardiovascular risk markers
4 has different effects depending upon gonadal status
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