Recombinant Human Growth Hormone During Rehabilitation From Traumatic Brain Injury. (Growth-TBI)

• ClinicalTrials.gov Identifier: NCT00766038
• Recruitment Status: Completed
• First Posted: October 3, 2008
• Results First Posted: November 18, 2019
• Last Update Posted: November 18, 2019
• Sponsor: University of Pennsylvania
• Collaborator: Baylor Health Care System
• Information provided by (Responsible Party): Ramon Diaz-Arrastia, University of Pennsylvania

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Traumatic Brain Injury
• Interventions: Drug: Recombinant human Growth Hormone; Drug: Placebo
• Enrollment: 63

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Active Treatment With Recombinant Human Growth Hormone	Placebo Treatment
Arm/Group Description	The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment. Recombinant human Growth Hormone: 400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements	Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding. Placebo: SC injection daily
Period Title: Overall Study
Started	31	32
Completed	16	18
Not Completed	15	14
Reason Not Completed
Lost to Follow-up	15	14

Baseline Characteristics

Arm/Group Title		Treatment With Recombinant Human Growth Hormone	Placebo Treatment	Total
Arm/Group Description		The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment. Recombinant human Growth Hormone: 400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements	Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding. Placebo: SC injection daily	Total of all reporting groups
Overall Number of Baseline Participants		31	32	63
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	32 participants	63 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	31 100.0%	32 100.0%	63 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	31 participants	32 participants	63 participants
		32.2 (15.2)	30.1 (13.7)	31.1 (14.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	32 participants	63 participants
	Female	14 45.2%	15 46.9%	29 46.0%
	Male	17 54.8%	17 53.1%	34 54.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	32 participants	63 participants
	Hispanic or Latino	4 12.9%	4 12.5%	8 12.7%
	Not Hispanic or Latino	27 87.1%	28 87.5%	55 87.3%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	32 participants	63 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	3 9.7%	2 6.3%	5 7.9%
	White	28 90.3%	30 93.8%	58 92.1%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment [1]; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	31 participants	32 participants	63 participants
		31 100.0%	32 100.0%	63 100.0%
		[1] Measure Description: Dallas, Texas
Baseline IGF-1 level < 1 SD below expected mean; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	31 participants	32 participants	63 participants
		3 9.7%	3 9.4%	6 9.5%
Baseline L-Arginine stimulation test; Median (Inter-Quartile Range); Unit of measure: ng/mL
	Number Analyzed	31 participants	32 participants	63 participants
		2.2; (0.6 to 5.9)	1.2; (0.5 to 5.7)	1.3; (0.5 to 5.8)

Outcome Measures

1. Primary Outcome

Title	Functional Outcome 6 Months After Injury, as Measured by the Processing Speed Index
Description	Processing Speed Index ages standardized score. In this scale, higher scores represent better functioning, lower scores represent poorer function. 100 = mean of a normative population. 110 = 1 standard deviation above normal; 90 = 1 standard deviation below normal 120 = 2 standard deviations above normal; 80 = 2 standard deviations below normal
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	rhGH Treatment	Placebo Treament
Arm/Group Description:	The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment. Recombinant human Growth Hormone: 400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements	Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding. Placebo: SC injection daily
Overall Number of Participants Analyzed	31	32
Median (Inter-Quartile Range); Unit of Measure: Processing speed index standardized scor
	82.5; (73.0 to 96.0)	82.5; (79.0 to 99.0)

2. Secondary Outcome

Title	IGF-1 Levels.
Description	Serum levels of Insulin-Like Growth Factor-1.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Treatment With Recombinant Human Growth Hormone	Placebo Treatment
Arm/Group Description:	The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment. Recombinant human Growth Hormone: 400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements	Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding. Placebo: SC injection daily
Overall Number of Participants Analyzed	31	32
Median (Inter-Quartile Range); Unit of Measure: ng/mL
	245.5; (203.5 to 321.5)	173.0; (145.0 to 237.0)

3. Secondary Outcome

Title	Processing Speed Index 1 Year After Injury
Description	Processing Speed Index ages standardized score. In this scale, higher scores represent better functioning, lower scores represent poorer function. 100 = mean of a normative population. 110 = 1 standard deviation above normal; 90 = 1 standard deviation below normal 120 = 2 standard deviations above normal; 80 = 2 standard deviations below normal
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Treatment With Recombinant Human Growth Hormone	Placebo Treatment
Arm/Group Description:	The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment. Recombinant human Growth Hormone: 400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements	Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding. Placebo: SC injection daily
Overall Number of Participants Analyzed	31	32
Median (Inter-Quartile Range); Unit of Measure: Processing speed index standardized scor
	86.0; (76.0 to 111)	89.5; (81.0 to 99)

4. Secondary Outcome

Title	GH Response to L-arginine Stimulation at Baseline
Description	Measurement of serum GH levels over 90 minutes after administration of L-arginine
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Treatment With Recombinant Human Growth Hormone	Placebo Treatment
Arm/Group Description:	The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment. Recombinant human Growth Hormone: 400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements	Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding. Placebo: SC injection daily
Overall Number of Participants Analyzed	31	32
Median (Inter-Quartile Range); Unit of Measure: ng/mL
	2.2; (0.6 to 5.9)	1.2; (0.5 to 5.7)

5. Secondary Outcome

Title	IGF-1 Levels
Description	Serum IGF-1 levels at baseline for both treatment groups was correlated with the Processing Speed Index recorded at baseline, using Pearson's correlation coefficient. Perason's correlation coefficient is a measure of the linear correlation between two variables X and Y. It has a value between +1 and -1, where 1 is total positive linear correlation, 0 is no linear correlation, and -1 is total negative linear correlation.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Treatment With Recombinant Human Growth Hormone	Placebo Treatment
Arm/Group Description:	The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment. Recombinant human Growth Hormone: 400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements	Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding. Placebo: SC injection daily
Overall Number of Participants Analyzed	31	32
Measure Type: Number; Unit of Measure: Pearson's correlation coefficient
	0.1	0.1

6. Secondary Outcome

Title	Rates of Diabetes Mellitus, Arthralgias, or Peripheral Edema.
Description	Rates of diabetes mellitus, arthralgias, or peripheral edema between rhGH treatment and placebo.
Time Frame	4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Treatment With Recombinant Human Growth Hormone	Placebo Treatment
Arm/Group Description:	The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment. Recombinant human Growth Hormone: 400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements	Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding. Placebo: SC injection daily
Overall Number of Participants Analyzed	31	32
Measure Type: Count of Participants; Unit of Measure: Participants
Diabetes mellitus	0 0.0%	0 0.0%
Arthralgia	2 6.5%	6 18.8%
Peripheral edema	0 0.0%	1 3.1%
None	29 93.5%	25 78.1%

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Recombinant Human Growth Hormone		Placebo Treatment
Arm/Group Description	The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment. Recombinant human Growth Hormone: 400 micrograms/day SC for 6 months. Dose adjusted based on serum IGF-1 measurements		Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding. Placebo: SC injection daily
All-Cause Mortality
	Recombinant Human Growth Hormone		Placebo Treatment
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/31 (0.00%)		0/32 (0.00%)
Serious Adverse Events
	Recombinant Human Growth Hormone		Placebo Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/31 (6.45%)		2/32 (6.25%)
Nervous system disorders
seizure † [1]	2/31 (6.45%)		2/32 (6.25%)
† Indicates events were collected by systematic assessment; [1] Patients with TBI are at high risk for post-traumatic seizures. Seizure in participants in this study are an expected adverse event
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Recombinant Human Growth Hormone		Placebo Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/31 (38.71%)		15/32 (46.88%)
General disorders
Elective Surgery †	6/31 (19.35%)	31	4/32 (12.50%)	32
Dry mouth †	1/31 (3.23%)	31	3/32 (9.38%)	32
Musculoskeletal and connective tissue disorders
Arthralgia	2/31 (6.45%)	2	6/32 (18.75%)	6
Myalgia †	1/31 (3.23%)	31	6/32 (18.75%)	32
Nervous system disorders
Headache †	1/31 (3.23%)	31	3/32 (9.38%)	32
Drowsiness †	1/31 (3.23%)	31	1/32 (3.13%)	32
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

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.

Results Point of Contact

• Name/Title: Ramon Diaz-Arrastia
• Organization: University of Pennsylvania
• Phone: 215-662-9732
• EMail: Ramon.Diaz-Arrastia@uphs.upenn.edu

• Responsible Party: Ramon Diaz-Arrastia, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT00766038
• Other Study ID Numbers: NTTBIMS-GH RCT; NIDRR H133A07002708; Pfizer GA62816O
• First Submitted: September 30, 2008
• First Posted: October 3, 2008
• Results First Submitted: January 15, 2019
• Results First Posted: November 18, 2019
• Last Update Posted: November 18, 2019