Ignite Creation Date:
2024-05-05 @ 5:28 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00462475
Status:
COMPLETED
Last Update Posted:
2007-10-16
First Post:
2007-04-18
Brief Title:
Effect of 5 Years of GH Replacement on Atherosclerosis
Sponsor:
Federico II University
Organization:
Federico II University
Study Overview
Official Title:
Phase 4 Study of Recombinant GH on Intima-Media Thickness at Common Carotids and on Cardiovascular Risk Factors in Hypopituitary Patients
Status:
COMPLETED
Status Verified Date:
2007-10
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:
5yrGH
Brief Summary:
Adult patients with hypopituitarism under adequate conventional hormone replacement therapy have reduced life expectancy due to excess vascular events 1-4 Deficiency in GH secretion GHD is likely to play a major role in determining the excess mortality since it is associated with lipid abnormalities visceral adiposity glucose intolerance insulin resistance hypertension cardiac abnormalities and increased intima-media thickness IMT at major arteries 5
Beneficial effects of growth hormone GH replacement on cardiovascular risk factors have been demonstrated in several studies of hypopituitary GHD patients 5 GH replacement improves body composition and lipid profile 5 it is accepted that management of dyslipidaemia is crucial in primary and secondary prevention of cardiovascular disease and part of the excess vascular risk associated with hypopituitarism is likely to be due to dyslipidaemia 6 A meta-analysis of blinded randomized placebo-controlled trials with low doses and long-duration GH treatment showed that GH replacement has beneficial effects on cardiovascular risk by improving lean and fat body mass total and LDL cholesterol levels and diastolic blood pressure 7 Besides GH replacement also induces improvement in cardiovascular markers 8 and cardiac performance 9 In small cohorts of GHD adults beneficial effects of GH replacement for 6-24 mos have also been reported on surrogate parameters of atherosclerosis such as intima-media thickness IMT at major arteries 10-13 while 6 months of GH deprivation is associated with an impairment of the cardiovascular risk profile 12 In a consistent series of men and women with hypopituitarism we reported however that two years of GH replacement is not adequate to normalize IMT levels at common carotid arteries 13
To give further insights on the likelihood of reversal of early atherosclerosis in severe GHD patients after prolonged GH replacement we designed this 5-yr prospective controlled study Only men aged 50 yrs and with severe GHD were enrolled to avoid gender and aging interference 13 Main outcome measure was IMT at common carotid arteries secondary measure was prevalence of insulin-resistance syndrome according with the American College of Endocrinology 14
Beneficial effects of growth hormone GH replacement on cardiovascular risk factors have been demonstrated in several studies of hypopituitary GHD patients 5 GH replacement improves body composition and lipid profile 5 it is accepted that management of dyslipidaemia is crucial in primary and secondary prevention of cardiovascular disease and part of the excess vascular risk associated with hypopituitarism is likely to be due to dyslipidaemia 6 A meta-analysis of blinded randomized placebo-controlled trials with low doses and long-duration GH treatment showed that GH replacement has beneficial effects on cardiovascular risk by improving lean and fat body mass total and LDL cholesterol levels and diastolic blood pressure 7 Besides GH replacement also induces improvement in cardiovascular markers 8 and cardiac performance 9 In small cohorts of GHD adults beneficial effects of GH replacement for 6-24 mos have also been reported on surrogate parameters of atherosclerosis such as intima-media thickness IMT at major arteries 10-13 while 6 months of GH deprivation is associated with an impairment of the cardiovascular risk profile 12 In a consistent series of men and women with hypopituitarism we reported however that two years of GH replacement is not adequate to normalize IMT levels at common carotid arteries 13
To give further insights on the likelihood of reversal of early atherosclerosis in severe GHD patients after prolonged GH replacement we designed this 5-yr prospective controlled study Only men aged 50 yrs and with severe GHD were enrolled to avoid gender and aging interference 13 Main outcome measure was IMT at common carotid arteries secondary measure was prevalence of insulin-resistance syndrome according with the American College of Endocrinology 14
Detailed Description:
This is an observational5-yr prospective controlled study At study entry all subjects underwent serum assay of IGF-I systolic and diastolic blood pressure SBP DBP measurement total- and HDL-cholesterol triglycerides glucose and insulin level after an overnight fasting and common carotid arteries ultrasonography The oral glucose load oGTT was performed by measuring blood glucose every 30 minutes for 2 hours after the oral administration of 75 g of glucose diluted in 250 ml of saline solution The conversion factors mgdl to mmoll for lipids and glucose were as follows cholesterol 002586 triglycerides 001129 and glucose 005551 According with previous studies 1319-21 blood pressure was measured at the right arm with the subjects in relaxed sitting position The average of six measurements three taken by each of two examiners in the same day between 800-900 in the morning with a mercury sphygmomanometer was used in all analysis
In the patients all parameters and carotid ultrasonography were re-evaluated after 12 24 36 48 and 60 months while in controls they were re-evaluated after 60 months
At study entry and at study end in all of the patients and controls the prevalence of insulin-resistance syndrome IRS was evaluated according with the American College of Endocrinology 14 based on the presence of at least two criteria of the following triglycerides levels 17 mmolliter HDL-cholesterol levels 10 mmolliter blood pressure above 13085 mmHg fasting glucose between 61 and 7 mmolliter or 2 hr after oGTT between 77 and 111 mmolliter
In the patients all parameters and carotid ultrasonography were re-evaluated after 12 24 36 48 and 60 months while in controls they were re-evaluated after 60 months
At study entry and at study end in all of the patients and controls the prevalence of insulin-resistance syndrome IRS was evaluated according with the American College of Endocrinology 14 based on the presence of at least two criteria of the following triglycerides levels 17 mmolliter HDL-cholesterol levels 10 mmolliter blood pressure above 13085 mmHg fasting glucose between 61 and 7 mmolliter or 2 hr after oGTT between 77 and 111 mmolliter
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