Adult Growth Hormone Deficiency and Cardiovascular Risk

Assessment of Cardiovascular Risk Markers in GH Deficient Patients With Nonsecreting Pituitary Adenomas

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.

Study Overview

• Status: Terminated
• Conditions: Growth Hormone Deficiency
• Intervention / Treatment: Procedure: Blood draws; Drug: growth hormone releasing hormone (GHRH) & arginine; Procedure: Carotid ultrasound; Procedure: MRI; Procedure: Endothelial cell biopsy

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.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: A - Normal growth hormone secretion; Patients who have undergone transsphenoidal surgery for a pituitary adenoma and have normal growth hormone secretion: Subjects will undergo a clinical exam with vital signs and blood draws, anthropometric measurements and skin fold thickness assessments. Subjects will also undergo GH stimulation testing with growth hormone releasing hormone (GHRH) & arginine, MRI and MR spectroscopy, carotid ultrasound, and have an endothelial cell biopsy.	Procedure: Blood draws; Subjects will have serum cardiovascular markers assessed; Drug: growth hormone releasing hormone (GHRH) & 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 - Growth hormone deficient; Patients who have undergone transsphenoidal surgery for pituitary adenoma who are growth hormone deficient: Subjects will undergo a clinical exam with vital signs and blood draws, anthropometric measurements and skin fold thickness assessments. Subjects will also undergo GH stimulation testing with growth hormone releasing hormone (GHRH) & arginine, MRI and MR spectroscopy, carotid ultrasound, and have an endothelial cell biopsy.	Procedure: Blood draws; Subjects will have serum cardiovascular markers assessed; Drug: growth hormone releasing hormone (GHRH) & 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-reactive Protein (CRP) Levels	C-reactive protein (CRP) levels in GH sufficient and GH deficient participants	Day 1
Homocysteine Level	Homocytsteine levels in GH sufficient and GH deficient participants	Day 1
Total Cholesterol Level	Total cholesterol levels in GH sufficient and GH deficient participants	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Fat Measured by DXA DEXA	Percentage of total body fat and trunk fat as measured by DXA	Day 1
Lean Body Mass by DXA DEXA	Lean body mass as measured by DXA	Day 1
Insulin Sensitivity as Assessed by Fasting Insulin Levels	Insulin sensitivity as assessed by fasting insulin levels	Day 1
Glucose Levels as Assessed by an Oral Glucose Tolerance Test	Glucose levels as assessed by an oral glucose tolerance test	Day 1
Endothelial Function as Assessed by Flow Mediated Dilatation and Endothelial Cell Biopsy	Endothelial function as assessed by flow mediated dilatation and endothelial cell biopsy for measurement of inflammatory markers.	Day 1
Carotid Intimal-medial Thickness Studies as Assessed by Ultrasound	Carotid intimal-medial thickness studies will be measured by ultrasound	Year 1
Intramyocellular Lipid Content Using MRI and MR Spectroscopy	Intramyocellular lipid content using MRI and MR spectroscopy of the soleus muscle was performed.	Day 1
Intrahepatic Lipid Content Using MRI and MR Spectroscopy	Intrahepatic lipid (IHL) content using MRI and MR spectroscopy of the liver was performed.	Day 1

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Study Director: John C Ausiello, MD, Columbia University

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (ACTUAL): March 1, 2010
• Study Completion (ACTUAL): May 1, 2011

Study Registration Dates

• First Submitted: June 16, 2008
• First Submitted That Met QC Criteria: July 22, 2008
• First Posted (ESTIMATE): July 23, 2008

Study Record Updates

• Last Update Posted (ACTUAL): November 16, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Growth hormone
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Dwarfism, Pituitary; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones; Growth Hormone-Releasing Hormone
• Other Study ID Numbers: AAAB9681 (Serono-001); Serono-001 (OTHER: protocol)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No