Adult Growth Hormone Deficiency and Cardiovascular Risk - Full Text View

Purpose

This protocol will assess the cardiovascular risk associated with growth hormone deficiency in adults. We will use multiple modalities to assess risk for heart attacks or strokes including blood work, ultrasound, MRI and endothelial cell biopsies in both patients who are growth hormone deficient and in patients with normal growth hormone secretion. We hypothesize that adults with growth hormone deficiency will have results suggestive of an increased risk for cardiovascular disease.

Condition	Intervention
Growth Hormone Deficiency	Procedure: Blood draws Drug: Growth hormone releasing hormone (GHRH) and arginine Procedure: Carotid ultrasound Procedure: MRI Procedure: Endothelial cell biopsy

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label
Official Title:	Assessment of Cardiovascular Risk Markers in GH Deficient Patients With Nonsecreting Pituitary Adenomas

Resource links provided by NLM:

Genetics Home Reference related topics: combined pituitary hormone deficiency isolated growth hormone deficiency metatropic dysplasia pseudoachondroplasia

MedlinePlus related topics: Diabetes Medicines

Drug Information available for: Arginine Arginine Hydrochloride Somatropin

U.S. FDA Resources

Further study details as provided by Columbia University:

Primary Outcome Measures:

Serum cardiovascular risk markers including lipids, CRP, IL-6 and homocysteine [ Time Frame: once ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percentage of total body fat, trunk fat and lean body mass by DEXA [ Time Frame: once ] [ Designated as safety issue: No ]
Insulin sensitivity as assessed by fasting insulin and glucose levels and by an oral glucose tolerance test [ Time Frame: once ] [ Designated as safety issue: No ]
Endothelial function as assessed by flow mediated dilatation and endothelial cell biopsy [ Time Frame: once ] [ Designated as safety issue: No ]
Carotid intimal-medial thickness studies as assessed by ultrasound [ Time Frame: once ] [ Designated as safety issue: No ]
Intramyocellular and intrahepatic lipid content using MRI and MR spectroscopy [ Time Frame: once ] [ Designated as safety issue: No ]

Enrollment:	8
Study Start Date:	February 2007
Study Completion Date:	May 2011
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: A Patients who have undergone transsphenoidal surgery for a pituitary adenoma and have normal growth hormone secretion.	Procedure: Blood draws Subjects will have serum cardiovascular markers assessed Drug: Growth hormone releasing hormone (GHRH) and arginine Subjects will receive GHRH and arginine intravenously and then have blood drawn at frequent intervals over a 90 minutes to assess growth hormone secretion. Procedure: Carotid ultrasound Subjects will have an ultrasound of their neck to assess their carotid arteries to look for intima-medial thickness. Procedure: MRI Subjects will have MRI and MR spectroscopy of the abdomen and lower extremities to assess for fat in internal organs and muscle. Procedure: Endothelial cell biopsy Subjects will undergo endothelial cell biopsies to harvest endothelial cells to study. It will occur once and takes approximately 20 minutes. Patients will have an iv placed and then a sterile wire is passed back and forth in the iv a couple of times. Three wires are passed.
Active Comparator: B Patients who have undergone transsphenoidal surgery for pituitary adenoma who are growth hormone deficient.	Procedure: Blood draws Subjects will have serum cardiovascular markers assessed Drug: Growth hormone releasing hormone (GHRH) and arginine Subjects will receive GHRH and arginine intravenously and then have blood drawn at frequent intervals over a 90 minutes to assess growth hormone secretion. Procedure: Carotid ultrasound Subjects will have an ultrasound of their neck to assess their carotid arteries to look for intima-medial thickness. Procedure: MRI Subjects will have MRI and MR spectroscopy of the abdomen and lower extremities to assess for fat in internal organs and muscle. Procedure: Endothelial cell biopsy Subjects will undergo endothelial cell biopsies to harvest endothelial cells to study. It will occur once and takes approximately 20 minutes. Patients will have an iv placed and then a sterile wire is passed back and forth in the iv a couple of times. Three wires are passed.

Arms

Assigned Interventions

Active Comparator: A

Patients who have undergone transsphenoidal surgery for a pituitary adenoma and have normal growth hormone secretion.

Procedure: Blood draws

Subjects will have serum cardiovascular markers assessed

Drug: Growth hormone releasing hormone (GHRH) and arginine

Subjects will receive GHRH and arginine intravenously and then have blood drawn at frequent intervals over a 90 minutes to assess growth hormone secretion.

Procedure: Carotid ultrasound

Subjects will have an ultrasound of their neck to assess their carotid arteries to look for intima-medial thickness.

Procedure: MRI

Subjects will have MRI and MR spectroscopy of the abdomen and lower extremities to assess for fat in internal organs and muscle.

Procedure: Endothelial cell biopsy

Subjects will undergo endothelial cell biopsies to harvest endothelial cells to study. It will occur once and takes approximately 20 minutes. Patients will have an iv placed and then a sterile wire is passed back and forth in the iv a couple of times. Three wires are passed.

Active Comparator: B

Patients who have undergone transsphenoidal surgery for pituitary adenoma who are growth hormone deficient.

Procedure: Blood draws

Subjects will have serum cardiovascular markers assessed

Drug: Growth hormone releasing hormone (GHRH) and arginine

Subjects will receive GHRH and arginine intravenously and then have blood drawn at frequent intervals over a 90 minutes to assess growth hormone secretion.

Procedure: Carotid ultrasound

Subjects will have an ultrasound of their neck to assess their carotid arteries to look for intima-medial thickness.

Procedure: MRI

Subjects will have MRI and MR spectroscopy of the abdomen and lower extremities to assess for fat in internal organs and muscle.

Procedure: Endothelial cell biopsy

Subjects will undergo endothelial cell biopsies to harvest endothelial cells to study. It will occur once and takes approximately 20 minutes. Patients will have an iv placed and then a sterile wire is passed back and forth in the iv a couple of times. Three wires are passed.

Detailed Description:

Subjects will first be tested for possible growth hormone deficiency. This will be done by administering two intravenous medications that should stimulate growth hormone secretion and we will measure growth hormone in the blood every 30 minutes following the administration. Once we have the results on enough subjects we will split the cohort into those subjects who are growth hormone deficient and those who have normal growth hormone. The two groups will each undergo various tests all designed to assess some component of cardiovascular risk. Ultimately we will compare the results of each test to see if those who are growth hormone deficient have an increased risk for cardiovascular disease.

Eligibility

Ages Eligible for Study:	19 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adults 19 years or older who have undergone transsphenoidal surgery for a clinically non-secreting pituitary adenoma

Exclusion Criteria:

Currently taking growth hormone, radiation therapy in the past 5 years, changes in dose of other pituitary hormone replacement therapy in past 3 months, taking hydrocortisone (or its equivalent) at a dose of > 30 mg/day, pregnant or nursing women

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00720902

Locations

United States, New York
Columbia University, College of Physicians and Surgeons
New York, New York, United States, 10032

Sponsors and Collaborators

Columbia University

Investigators

Study Director:

John C Ausiello, MD

Columbia University

More Information

No publications provided

Responsible Party:	Columbia University
ClinicalTrials.gov Identifier:	NCT00720902 History of Changes
Other Study ID Numbers:	AAAB9681 (Serono-001), Serono-001
Study First Received:	June 16, 2008
Last Updated:	May 14, 2013
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Dwarfism, Pituitary
Endocrine System Diseases
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Hypopituitarism
Pituitary Diseases

Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hormones
Growth Hormone-Releasing Hormone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013