Growth Hormone Deficiency Clinical Trial
— 5yrGHOfficial title:
Phase 4 Study of Recombinant GH on Intima-Media Thickness at Common Carotids and on Cardiovascular Risk Factors in Hypopituitary Patients
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).
Status | Completed |
Enrollment | 20 |
Est. completion date | December 2006 |
Est. primary completion date | |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Male |
Age group | 18 Years to 50 Years |
Eligibility |
Inclusion Criteria: - male gender - age <50 yrs to limit the effect of aging; - body mass index <30 Kg/m2; - no familial or personal history of cardiovascular diseases; - no concomitant treatment with drugs known to interfere with glucose or lipid metabolism or to influence blood pressure at the time of study entry; - no previous GH treatment Exclusion Criteria: - female gender - age >50 yrs; - body mass index =30; - familial or personal history of cardiovascular diseases; - previous and present treatments with drugs known to interfere with glucose or lipid metabolism or to influence blood pressure; - previous GH treatment in adult age - GHD of childhood onset - GHD due to previous Cushing's disease |
Observational Model: Case Control, Time Perspective: Prospective
Country | Name | City | State |
---|---|---|---|
Italy | Department of Molecular and Clinical Endocirnology and Oncology University Federico II of Naples | Naples |
Lead Sponsor | Collaborator |
---|---|
Federico II University |
Italy,
Abdu TA, Neary R, Elhadd TA, Akber M, Clayton RN. Coronary risk in growth hormone deficient hypopituitary adults: increased predicted risk is due largely to lipid profile abnormalities. Clin Endocrinol (Oxf). 2001 Aug;55(2):209-16. Erratum in: Clin Endocr — View Citation
Aimaretti G, Corneli G, Razzore P, Bellone S, Baffoni C, Arvat E, Camanni F, Ghigo E. Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults. J — View Citation
Bates AS, Van't Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. 1996 Mar;81(3):1169-72. — View Citation
Borson-Chazot F, Serusclat A, Kalfallah Y, Ducottet X, Sassolas G, Bernard S, Labrousse F, Pastene J, Sassolas A, Roux Y, Berthezène F. Decrease in carotid intima-media thickness after one year growth hormone (GH) treatment in adults with GH deficiency. J — View Citation
Bülow B, Hagmar L, Mikoczy Z, Nordström CH, Erfurth EM. Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol (Oxf). 1997 Jan;46(1):75-81. — View Citation
Colao A, Cerbone G, Pivonello R, Aimaretti G, Loche S, Di Somma C, Faggiano A, Corneli G, Ghigo E, Lombardi G. The growth hormone (GH) response to the arginine plus GH-releasing hormone test is correlated to the severity of lipid profile abnormalities in — View Citation
Colao A, Di Somma C, Cuocolo A, Filippella M, Rota F, Acampa W, Savastano S, Salvatore M, Lombardi G. The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: an observational — View Citation
Colao A, Di Somma C, Cuocolo A, Spinelli L, Acampa W, Spiezia S, Rota F, Savanelli MC, Lombardi G. Does a gender-related effect of growth hormone (GH) replacement exist on cardiovascular risk factors, cardiac morphology, and performance and atherosclerosi — View Citation
Colao A, di Somma C, Cuocolo A, Spinelli L, Tedesco N, Pivonello R, Bonaduce D, Salvatore M, Lombardi G. Improved cardiovascular risk factors and cardiac performance after 12 months of growth hormone (GH) replacement in young adult patients with GH defici — View Citation
Colao A, Di Somma C, Filippella M, Rota F, Pivonello R, Orio F, Vitale G, Lombardi G. Insulin-like growth factor-1 deficiency determines increased intima-media thickness at common carotid arteries in adult patients with growth hormone deficiency. Clin End — View Citation
Colao A, di Somma C, Pivonello R, Cuocolo A, Spinelli L, Bonaduce D, Salvatore M, Lombardi G. The cardiovascular risk of adult GH deficiency (GHD) improved after GH replacement and worsened in untreated GHD: a 12-month prospective study. J Clin Endocrinol — View Citation
Colao A, Di Somma C, Pivonello R, Loche S, Aimaretti G, Cerbone G, Faggiano A, Corneli G, Ghigo E, Lombardi G. Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab. 1999 Jun;8 — View Citation
Colao A, Di Somma C, Rota F, Pivonello R, Savanelli MC, Spiezia S, Lombardi G. Short-term effects of growth hormone (GH) treatment or deprivation on cardiovascular risk parameters and intima-media thickness at carotid arteries in patients with severe GH d — View Citation
Colao A, Di Somma C, Savanelli MC, De Leo M, Lombardi G. Beginning to end: cardiovascular implications of growth hormone (GH) deficiency and GH therapy. Growth Horm IGF Res. 2006 Jul;16 Suppl A:S41-8. Epub 2006 May 11. Review. — View Citation
Colao A, Marzullo P, Di Somma C, Lombardi G. Growth hormone and the heart. Clin Endocrinol (Oxf). 2001 Feb;54(2):137-54. Review. — View Citation
Einhorn D, Reaven GM, Cobin RH, Ford E, Ganda OP, Handelsman Y, Hellman R, Jellinger PS, Kendall D, Krauss RM, Neufeld ND, Petak SM, Rodbard HW, Seibel JA, Smith DA, Wilson PW. American College of Endocrinology position statement on the insulin resistance — View Citation
Gola M, Bonadonna S, Doga M, Giustina A. Clinical review: Growth hormone and cardiovascular risk factors. J Clin Endocrinol Metab. 2005 Mar;90(3):1864-70. Epub 2004 Dec 7. Review. — View Citation
Maison P, Griffin S, Nicoue-Beglah M, Haddad N, Balkau B, Chanson P; Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials. Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a Metaanalysis of Blinded, — View Citation
Pfeifer M, Verhovec R, Zizek B, Prezelj J, Poredos P, Clayton RN. Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults. J Clin Endocrinol Metab. 1999 Feb;84(2):453-7. — View Citation
Rosén T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990 Aug 4;336(8710):285-8. — View Citation
Tomlinson JW, Holden N, Hills RK, Wheatley K, Clayton RN, Bates AS, Sheppard MC, Stewart PM. Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet. 2001 Feb 10;357(9254):425-31. — View Citation
* Note: There are 21 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Intima-media thickness at common carotid arteries at baseline and after 5 years | 5 yrs | ||
Secondary | Prevalence of insulin resistance (IR) syndrome (IRS) and LDL/HDL-cholesterol ratio at baseline and after 5 years | 5 yrs |
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