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Effect of 5 Years of GH Replacement on Atherosclerosis (5yrGH)

This study has been completed.
Sponsor:
Information provided by:
Federico II University
ClinicalTrials.gov Identifier:
NCT00462475
First received: April 18, 2007
Last updated: October 15, 2007
Last verified: October 2007
  Purpose

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).


Condition Intervention Phase
Hypopituitarism
Pituitary Tumors
Growth Hormone Deficiency
Drug: Recombinant Growth Hormone, Genotropin (Pfizer)
Phase 4

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Phase 4 Study of Recombinant GH on Intima-Media Thickness at Common Carotids and on Cardiovascular Risk Factors in Hypopituitary Patients

Resource links provided by NLM:


Further study details as provided by Federico II University:

Primary Outcome Measures:
  • Intima-media thickness at common carotid arteries at baseline and after 5 years [ Time Frame: 5 yrs ]

Secondary Outcome Measures:
  • Prevalence of insulin resistance (IR) syndrome (IRS) and LDL/HDL-cholesterol ratio at baseline and after 5 years [ Time Frame: 5 yrs ]

Enrollment: 20
Study Start Date: January 1996
Study Completion Date: December 2006
Detailed Description:

This is an observational,5-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 (mg/dl to mmol/l) for lipids and glucose were as follows: cholesterol 0.02586, triglycerides 0.01129, and glucose 0.05551. According with previous studies (13,19-21) 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 8.00-9.00 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 ≥1.7 mmol/liter, HDL-cholesterol levels ≤1.0 mmol/liter, blood pressure above 130/85 mmHg, fasting glucose between 6.1 and 7 mmol/liter or 2 hr after oGTT between 7.7 and 11.1 mmol/liter.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Three groups are studied: 1) Males with severe GHD undergoing GH replacement; 2) Males with severe GHD who did not undergo GH replacement because of either refusal or presence of risk factors for this treatment; 2) control men, age-matched with the patients.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00462475

Locations
Italy
Department of Molecular and Clinical Endocirnology and Oncology University Federico II of Naples
Naples, Italy, 80131
Sponsors and Collaborators
Federico II University
Investigators
Principal Investigator: Annamaria AL Colao, Prof. University "Federico II"
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00462475     History of Changes
Other Study ID Numbers: NeuroendoUnit-3
Study First Received: April 18, 2007
Last Updated: October 15, 2007
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency

Keywords provided by Federico II University:
GH
IGF-I
GH deficiency
Atherosclerosis
Insulin resistance syndrome

Additional relevant MeSH terms:
Atherosclerosis
Dwarfism, Pituitary
Hypopituitarism
Pituitary Neoplasms
Arterial Occlusive Diseases
Arteriosclerosis
Bone Diseases
Bone Diseases, Developmental
Bone Diseases, Endocrine
Brain Diseases
Brain Neoplasms
Cardiovascular Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Dwarfism
Endocrine Gland Neoplasms
Endocrine System Diseases
Hypothalamic Diseases
Hypothalamic Neoplasms
Musculoskeletal Diseases
Neoplasms
Neoplasms by Site
Nervous System Diseases
Nervous System Neoplasms
Pituitary Diseases
Supratentorial Neoplasms
Vascular Diseases

ClinicalTrials.gov processed this record on November 20, 2014