Growth Hormone Deficiency
Conditions
Keywords
Growth hormone
Brief summary
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.
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.
Interventions
PROCEDUREBlood draws
Subjects will have serum cardiovascular markers assessed
DRUGgrowth 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.
PROCEDURECarotid ultrasound
Subjects will have an ultrasound of their neck to assess their carotid arteries to look for intima-medial thickness.
PROCEDUREMRI
Subjects will have MRI and MR spectroscopy of the abdomen and lower extremities to assess for fat in internal organs and muscle.
PROCEDUREEndothelial 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.
Sponsors
Columbia University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C-reactive Protein (CRP) Levels | Day 1 | C-reactive protein (CRP) levels in GH sufficient and GH deficient participants |
| Homocysteine Level | Day 1 | Homocytsteine levels in GH sufficient and GH deficient participants |
| Total Cholesterol Level | Day 1 | Total cholesterol levels in GH sufficient and GH deficient participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose Levels as Assessed by an Oral Glucose Tolerance Test | Day 1 | Glucose levels as assessed by an oral glucose tolerance test |
| Endothelial Function as Assessed by Flow Mediated Dilatation and Endothelial Cell Biopsy | Day 1 | Endothelial function as assessed by flow mediated dilatation and endothelial cell biopsy for measurement of inflammatory markers. |
| Percentage of Fat Measured by DXA DEXA | Day 1 | Percentage of total body fat and trunk fat as measured by DXA |
| Intramyocellular Lipid Content Using MRI and MR Spectroscopy | Day 1 | Intramyocellular lipid content using MRI and MR spectroscopy of the soleus muscle was performed. |
| Intrahepatic Lipid Content Using MRI and MR Spectroscopy | Day 1 | Intrahepatic lipid (IHL) content using MRI and MR spectroscopy of the liver was performed. |
| Carotid Intimal-medial Thickness Studies as Assessed by Ultrasound | Year 1 | Carotid intimal-medial thickness studies will be measured by ultrasound |
| Lean Body Mass by DXA DEXA | Day 1 | Lean body mass as measured by DXA |
| Insulin Sensitivity as Assessed by Fasting Insulin Levels | Day 1 | Insulin sensitivity as assessed by fasting insulin levels |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GH Sufficient Participants Participants with normal growth hormone secretion. | 4 |
| GH Deficient Participants Participants with growth hormone secretion deficiency. | 3 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Unable to perform testing, lack of test agent and the Study terminated | 3 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | GH Sufficient Participants | GH Deficient Participants | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 0 / 4 | 0 / 3 |
| serious Total, serious adverse events | 0 / 4 | 0 / 3 |
Outcome results
Primary
C-reactive Protein (CRP) Levels
C-reactive protein (CRP) levels in GH sufficient and GH deficient participants
Time frame: Day 1
Population: Study was terminated early due to insufficient enrollment and lack of GHRH study medication to be administered. The medication became unavailable in the US after enrollment began, but before that testing could be performed. Without that testing, further classification of subjects as sufficient or deficient could not be performed and the remainder of the tests could not be done. Partial testing was only done on 3 GH deficient subjects and the results of this are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GH Deficient Participants | C-reactive Protein (CRP) Levels | 14.46 ng/dL | Standard Deviation 14.9 |
Primary
Homocysteine Level
Homocytsteine levels in GH sufficient and GH deficient participants
Time frame: Day 1
Population: Study was terminated early due to insufficient enrollment and lack of GHRH study medication to be administered. The medication became unavailable in the US after enrollment began, but before that testing could be performed. Without that testing, further classification of subjects as sufficient or deficient could not be performed and the remainder of the tests could not be done. Partial testing was only done on 3 GH deficient subjects and the results of this are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GH Deficient Participants | Homocysteine Level | 8.04 micromol/L | Standard Deviation 0.9 |
Primary
Total Cholesterol Level
Total cholesterol levels in GH sufficient and GH deficient participants
Time frame: Day 1
Population: Study was terminated early due to insufficient enrollment and lack of GHRH study medication to be administered. The medication became unavailable in the US after enrollment began, but before that testing could be performed. Without that testing, further classification of subjects as sufficient or deficient could not be performed and the remainder of the tests could not be done. Partial testing was only done on 3 GH deficient subjects and the results of this are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GH Deficient Participants | Total Cholesterol Level | 271 mg/dL | Standard Deviation 90.5 |
Secondary
Carotid Intimal-medial Thickness Studies as Assessed by Ultrasound
Carotid intimal-medial thickness studies will be measured by ultrasound
Time frame: Year 1
Population: Study was terminated early due to insufficient enrollment and lack of GHRH study medication to be administered. The medication became unavailable in the US after enrollment began, but before that testing could be performed. Without that testing, further classification of participants as sufficient or deficient could not be performed and the remainder of the tests could not be done. As a result, data were not collected for GH sufficient and GH deficient participants.
Secondary
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.
Time frame: Day 1
Population: Study was terminated early due to insufficient enrollment and lack of GHRH study medication to be administered. The medication became unavailable in the US after enrollment began, but before that testing could be performed. Without that testing, further classification of participants as sufficient or deficient could not be performed and the remainder of the tests could not be done. As a result, data were not collected for GH sufficient or GH deficient participants for this outcome measure
Secondary
Glucose Levels as Assessed by an Oral Glucose Tolerance Test
Glucose levels as assessed by an oral glucose tolerance test
Time frame: Day 1
Population: Study was terminated early due to insufficient enrollment and lack of GHRH study medication to be administered. The medication became unavailable in the US after enrollment began, but before that testing could be performed. Without that testing, further classification of subjects as sufficient or deficient could not be performed and the remainder of the tests could not be done. Partial testing was only done on 3 GH deficient subjects and the results of this are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GH Deficient Participants | Glucose Levels as Assessed by an Oral Glucose Tolerance Test | 91.33 mg/dL | Standard Deviation 4.163 |
Secondary
Insulin Sensitivity as Assessed by Fasting Insulin Levels
Insulin sensitivity as assessed by fasting insulin levels
Time frame: Day 1
Population: Study was terminated early due to insufficient enrollment and lack of GHRH study medication to be administered. The medication became unavailable in the US after enrollment began, but before that testing could be performed. Without that testing, further classification of subjects as sufficient or deficient could not be performed and the remainder of the tests could not be done. Partial testing was only done on 3 GH deficient subjects and the results of this are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GH Deficient Participants | Insulin Sensitivity as Assessed by Fasting Insulin Levels | 35.5 mIU/L | Standard Deviation 28.94 |
Secondary
Intrahepatic Lipid Content Using MRI and MR Spectroscopy
Intrahepatic lipid (IHL) content using MRI and MR spectroscopy of the liver was performed.
Time frame: Day 1
Population: Study was terminated early due to insufficient enrollment and lack of GHRH study medication to be administered. The medication became unavailable in the US after enrollment began, but before that testing could be performed. Without that testing, further classification of subjects as sufficient or deficient could not be performed and the remainder of the tests could not be done. Partial testing was only done on 3 GH deficient subjects and the results of this are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GH Deficient Participants | Intrahepatic Lipid Content Using MRI and MR Spectroscopy | 9.97 Percent water signal | Standard Deviation 7.17 |
Secondary
Intramyocellular Lipid Content Using MRI and MR Spectroscopy
Intramyocellular lipid content using MRI and MR spectroscopy of the soleus muscle was performed.
Time frame: Day 1
Population: Study was terminated early due to insufficient enrollment and lack of GHRH study medication to be administered. The medication became unavailable in the US after enrollment began, but before that testing could be performed. Without that testing, further classification of subjects as sufficient or deficient could not be performed and the remainder of the tests could not be done. Partial testing was only done on 3 GH deficient subjects and the results of this are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GH Deficient Participants | Intramyocellular Lipid Content Using MRI and MR Spectroscopy | 0.011763 Percent water signal | Standard Deviation 0.00159 |
Secondary
Lean Body Mass by DXA DEXA
Lean body mass as measured by DXA
Time frame: Day 1
Population: Study was terminated early due to insufficient enrollment and lack of GHRH study medication to be administered. The medication became unavailable in the US after enrollment began, but before that testing could be performed. Without that testing, further classification of subjects as sufficient or deficient could not be performed and the remainder of the tests could not be done. Partial testing was only done on 3 GH deficient subjects and the results of this are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GH Deficient Participants | Lean Body Mass by DXA DEXA | 46.67 kg | Standard Error 2.89 |
Secondary
Percentage of Fat Measured by DXA DEXA
Percentage of total body fat and trunk fat as measured by DXA
Time frame: Day 1
Population: Study was terminated early due to insufficient enrollment and lack of GHRH study medication to be administered. The medication became unavailable in the US after enrollment began, but before that testing could be performed. Without that testing, further classification of subjects as sufficient or deficient could not be performed and the remainder of the tests could not be done. Partial testing was only done on 3 GH deficient subjects and the results of this are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GH Deficient Participants | Percentage of Fat Measured by DXA DEXA | Total body fat | 42.33333333 Percent | Standard Error 8.73 |
| GH Deficient Participants | Percentage of Fat Measured by DXA DEXA | Trunk fat | 21 Percent | Standard Error 3.6 |