Growth Hormone and Endothelial Function in Children

• Sponsor: Ohio State University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00373386
• Collaborator: Nationwide Children's Hospital (Other)
• Enrollment: 9
• Location: 1
• Arm: 1
• Duration (Months): 35
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Growth Hormone Deficiency; Panhypopituitarism; Short Stature	Drug: growth hormone	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Growth Hormone and Endothelial Function in Children
• Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Jun 1, 2007
• Actual Study Completion Date: Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Growth Hormone Growth hormone treatment 0.3 mg/kg/min	Drug: growth hormone; Growth Hormone treatment

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Glucose [3 months]

   Plasma glucose

2. Insulin [3 months]

   Plasma insulin

3. HOMA [3 months]

   Insulin resistance

4. Triglycerides [3 months]

   Plasma Triglycerides

5. LDL [3 months]

   LDL level

6. HDL [3 months]

   Plasma HDL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ohio State University	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Ohio State University
• Nationwide Children's Hospital

Investigators

• Study Chair: Robert P Hoffman, MD, Ohio State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert Hoffman, Professor, Ohio State University
• ClinicalTrials.gov Identifier: NCT00373386
• Other Study ID Numbers: Peds15
• First Posted: Sep 8, 2006
• Last Update Posted: May 30, 2018
• Last Verified: Sep 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Robert Hoffman, Professor, Ohio State University: growth hormone; endothelial function
• Additional relevant MeSH terms: Dwarfism; Hormones

Study Results

Participant Flow

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	Growth hormone 0.3 mg/kg/week given 6 days per week
Period Title: Overall Study
STARTED	9
COMPLETED	9
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description
Overall Participants	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11.9 (2.4)
Sex: Female, Male (Count of Participants)
Female	1 11.1%
Male	8 88.9%
Region of Enrollment (participants) [Number]
United States	9 100%
Post occlusion forearm blood flow (ml/dl*min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ml/dl*min]	22.8 (9.9)
Glucose (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	82 (9)
insulin (uU/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [uU/ml]	5.7 (4.8)
Homa (mg*uU/dl*ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg*uU/dl*ml]	21 (21)
triglycerides (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	115 (150)
ldl (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	127 (51)
HDL (mg/dl) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dl]	44 (6)
SBP (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	96 (9)
DBP (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	47 (9)

Outcome Measures

1. Primary Outcome

Title	Reactive Hyperemic Response After 3 Months of Growth Hormone
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	9 subject (8 male 1 female). 8 with isolated GH deficiency (peak GH level less than 10 ng/ml in response to arginine-insulin stimulation with normal cortisol response and thyroid function tests) 1 with panhypopitutarism on cortisol and thyroxine replacement
Measure Participants	9
Mean (Standard Error) [ml/dl min]	21.077 (1.937)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments	compared with baseline
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.644
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Glucose
Description	Plasma glucose
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	9 subject (8 male 1 female). 8 with isolated GH deficiency (peak GH level less than 10 ng/ml in response to arginine-insulin stimulation with normal cortisol response and thyroid function tests) 1 with panhypopitutarism on cortisol and thyroxine replacement
Measure Participants	9
Mean (Standard Deviation) [mg/dl]	87 (9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments	Compared with baseline
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments	Versus baseline
	Method	t-test, 2 sided
	Comments	paired

3. Secondary Outcome

Title	Insulin
Description	Plasma insulin
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone
Arm/Group Description	Growth hormone treatment 0.3 mg/kg/min growth hormone: Growth Hormone treatment
Measure Participants	9
Mean (Standard Error) [uU/ml]	11.3 (6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments	Comparison to baseline
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	HOMA
Description	Insulin resistance
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	9 subjects will have either isolated GH deficiency (peak GH level less than 10 ng/ml in response to arginine-insulin stimulation with normal cortisol response and thyroid function tests) or growth hormone deficiency with other treated pituitary deficiencies.
Measure Participants	9
Mean (Standard Error) [mg uU/dl ml]	43 (8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments	Comparison with baseline
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Triglycerides
Description	Plasma Triglycerides
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	9 subjects will have either isolated GH deficiency (peak GH level less than 10 ng/ml in response to arginine-insulin stimulation with normal cortisol response and thyroid function tests) or growth hormone deficiency with other treated pituitary deficiencies.
Measure Participants	9
Mean (Standard Error) [mg/dl]	75 (20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments	Comparison with baseline
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.804
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	LDL
Description	LDL level
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	9 subjects will have either isolated GH deficiency (peak GH level less than 10 ng/ml in response to arginine-insulin stimulation with normal cortisol response and thyroid function tests) or growth hormone deficiency with other treated pituitary deficiencies.
Measure Participants	9
Mean (Standard Error) [mg/dl]	110 (9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments	Comparison with baseline
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.095
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	HDL
Description	Plasma HDL
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	9 subjects will have either isolated GH deficiency (peak GH level less than 10 ng/ml in response to arginine-insulin stimulation with normal cortisol response and thyroid function tests) or growth hormone deficiency with other treated pituitary deficiencies.
Measure Participants	9
Mean (Standard Error) [mg/dl]	47 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments	Comparison with baseline
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.648
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Immediate
Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	9 subjects will have either isolated GH deficiency (peak GH level less than 10 ng/ml in response to arginine-insulin stimulation with normal cortisol response and thyroid function tests) or growth hormone deficiency with other treated pituitary deficiencies.
All Cause Mortality
	Growth Hormone Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Growth Hormone Treatment
	Affected / at Risk (%)	# Events
Total	0/9 (0%)
Other (Not Including Serious) Adverse Events
	Growth Hormone Treatment
	Affected / at Risk (%)	# Events
Total	0/9 (0%)

Limitations/Caveats

Small sample size

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.