Growth Hormone Deficiency, Panhypopituitarism, Short Stature
Conditions
Keywords
growth hormone, endothelial function
Brief summary
Objective: This study is designed to determine whether growth hormone treatment in children 8 to 18 years of age alters function of the lining of the arteries. This may play a role in increasing or decreasing the risk of heart disease. Methods. Twenty children, for whom growth hormone therapy will be otherwise provided, will be studied before and 3 months after starting growth hormone. Subjects can be on other hormonal replacements but no other medications. Each study will be done in the fasting state. The blood vessel function will be determined by measuring the change in forearm blood flow before and after blocking flow to the arm for 5 minutes. Blood will be drawn after the test to measure glucose, insulin and fats.
Detailed description
The purpose of the research is to learn more about how the lining of arteries in the body (called the endothelium) is affected by growth hormone treatment in children and adolescents. Poor function by the blood vessels is associated with increased risk of heart disease or stroke. This research is being done because growth hormone treatment has been shown to make the endothelium work better in adults. Growth hormone treatment may have the same or different effects in children because the dose is larger in children. Children between 8 and 18 years who are to be started on growth hormone will be eligible to participate. Blood vessel function will be studied before starting growth hormone and 3 months after. This will be done by measuring blood flow to the arm before and after 5 min of stopping blood flow to the arm. The three months of growth hormone will be given free.
Interventions
DRUGgrowth hormone
Growth Hormone treatment
Sponsors
Nationwide Children's Hospital
Ohio State University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* isolated growth hormone deficiency (peak growth hormone level less than 10 ng/ml in response to arginine-insulin stimulation with cortisol responses and thyroid function tests), panhypopituitarism with appropriate thyroxine (normal free T4 level) and cortisol replacement (8-12 mg/m2/day) and non classic growth hormone deficiency (growth velocity less than 5 cm/year; peak growth hormone \>10 ng/ml).
Exclusion criteria
* Taking medications other than the appropriate hormonal replacement(L-thyroxine, cortisol, estrogen or testosterone, DDAVP)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reactive Hyperemic Response After 3 Months of Growth Hormone | 3 months | Forearm blood flow (FBF) was measured using strain gauge venous occlusion plethysmography using a Hokanson EC6 plethysmograph (DE Hokanson Inc, Bellevue, WA) in the left arm. With this technique sphygmomanometric cuffs were placed on the arm at the wrist and on the upper arm. During measurement the wrist cuff was inflated to 200 mmHg to occlude flow to the hand which is primarily skin blood flow and the upper arm cuff is inflated to 40 mmHG for 10 out of every 15 second to occlude venous return. FBF was obtained by measuring arm expansion with an indium-in-silastic strain gauge. Data was recorded using PowerLab and Chart 4.0 (AD Instruments, Grand Junction, CO) on a Power Mac G4 computer (Apple, Cupertino, CA).For each subject two minutes of baseline FBF were recorded and then the upper arm cuff was inflated to 200 mmHg pressure for five minutes to occlude flow to the arm. It was then released and forearm blood flow was measured for the next minute. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin | 3 months | Plasma insulin |
| HOMA | 3 months | Insulin resistance |
| Glucose | 3 months | Plasma glucose |
| LDL | 3 months | LDL level |
| HDL | 3 months | Plasma HDL |
| Triglycerides | 3 months | Plasma Triglycerides |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Growth Hormone Treatment | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Growth Hormone Treatment |
|---|---|
| Age, Continuous | 11.9 years STANDARD_DEVIATION 2.4 |
| DBP | 47 mmHg STANDARD_DEVIATION 9 |
| Glucose | 82 mg/dl STANDARD_DEVIATION 9 |
| HDL | 44 mg/dl STANDARD_DEVIATION 6 |
| Homa | 21 mg*uU/dl*ml STANDARD_DEVIATION 21 |
| insulin | 5.7 uU/ml STANDARD_DEVIATION 4.8 |
| ldl | 127 mg/dl STANDARD_DEVIATION 51 |
| Post occlusion forearm blood flow | 22.8 ml/dl*min STANDARD_DEVIATION 9.9 |
| Region of Enrollment United States | 9 participants |
| SBP | 96 mmHg STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 8 Participants |
| triglycerides | 115 mg/dl STANDARD_DEVIATION 150 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Reactive Hyperemic Response After 3 Months of Growth Hormone
Forearm blood flow (FBF) was measured using strain gauge venous occlusion plethysmography using a Hokanson EC6 plethysmograph (DE Hokanson Inc, Bellevue, WA) in the left arm. With this technique sphygmomanometric cuffs were placed on the arm at the wrist and on the upper arm. During measurement the wrist cuff was inflated to 200 mmHg to occlude flow to the hand which is primarily skin blood flow and the upper arm cuff is inflated to 40 mmHG for 10 out of every 15 second to occlude venous return. FBF was obtained by measuring arm expansion with an indium-in-silastic strain gauge. Data was recorded using PowerLab and Chart 4.0 (AD Instruments, Grand Junction, CO) on a Power Mac G4 computer (Apple, Cupertino, CA).For each subject two minutes of baseline FBF were recorded and then the upper arm cuff was inflated to 200 mmHg pressure for five minutes to occlude flow to the arm. It was then released and forearm blood flow was measured for the next minute.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone Treatment | Reactive Hyperemic Response After 3 Months of Growth Hormone | 21.077 ml/dl min | Standard Error 1.937 |
Comparison: compared with baselinep-value: 0.644t-test, 2 sided
Secondary
Glucose
Plasma glucose
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone Treatment | Glucose | 87 mg/dl | Standard Deviation 9 |
Comparison: Compared with baselinep-value: 0.018t-test, 2 sided
Secondary
HDL
Plasma HDL
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone Treatment | HDL | 47 mg/dl | Standard Error 3 |
Comparison: Comparison with baselinep-value: 0.648t-test, 2 sided
Secondary
HOMA
Insulin resistance
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone Treatment | HOMA | 43 mg uU/dl ml | Standard Error 8 |
Comparison: Comparison with baselinep-value: 0.004t-test, 2 sided
Secondary
Insulin
Plasma insulin
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone Treatment | Insulin | 11.3 uU/ml | Standard Error 6 |
Comparison: Comparison to baselinep-value: 0.04t-test, 2 sided
Secondary
LDL
LDL level
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone Treatment | LDL | 110 mg/dl | Standard Error 9 |
Comparison: Comparison with baselinep-value: 0.095t-test, 2 sided
Secondary
Triglycerides
Plasma Triglycerides
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone Treatment | Triglycerides | 75 mg/dl | Standard Error 20 |
Comparison: Comparison with baselinep-value: 0.804t-test, 2 sided