Growth Hormone Treatment on Phosphocreatine Recovery in Obesity

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01421589
• Collaborator: Pfizer (Industry)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 18
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

Obesity is associated with reduced growth hormone (GH) secretion. Reduced GH secretion in obesity is associated with increased cardiovascular disease risk. However, it is not yet known how reduced GH increases cardiovascular disease risk in obesity. The investigators hypothesize that reduced GH contributes to dysfunction of the mitochondria. Therefore, the investigators hypothesize that treatment of obese subjects with reduced GH secretion with GH will improve mitochondrial function and that this improvement in mitochondrial function will contribute, in part, to the effects of GH to improve metabolic parameters in obesity. The investigators propose to study skeletal muscle mitochondria in obese subjects with reduced GH secretion using magnetic resonance spectroscopy and muscle biopsies before and after treatment with GH.

Condition or Disease	Intervention/Treatment	Phase
Obese; Growth Hormone Secretion Abnormality	Drug: Growth hormone treatment	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effects of Short Term Growth Hormone Treatment on Skeletal Muscle Phosphocreatine Recovery in Obesity
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Growth Hormone	Drug: Growth hormone treatment; Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.

Outcome Measures

Primary Outcome Measures

1. Phosphocreatine Recovery [12-weeks]

   The primary objective of this study is to determine the effects of growth hormone on mitochondrial function as assessed by 31P-MRS in obese subjects with reduced GH secretion. Mitochondrial function was represented by ViPCr, a measure of phosphocreatine recovery after sub-maximal exercise. Univariate regression analyses was performed to assess the relationship between the change in skeletal muscle IGF-1 mRNA after 12 weeks treatment with rhGH to change in ViPCr.

Secondary Outcome Measures

1. Change in Circulating IGF-1 Concentration [Baseline and 12-weeks]

   Change in circulating IGF-1 from Baseline to 12-weeks is reported.

2. Change in Skeletal Muscle IGF-1 Gene Expression [Baseline and 12-weeks]

   Change in skeletal muscle IGF-1 gene mRNA expression from Baseline to 12-weeks is reported.

3. Change in Body Composition [Baseline and 12-weeks]

   Change in waist circumference from Baseline to 12-weeks is reported.

4. Change in Inflammatory Marker [Baseline and 12-weeks]

   Change in high sensitivity C-reactive protein (hsCRP) from Baseline to 12-weeks is reported.

5. Change in Insulin Sensitivity [Baseline and 12-weeks]

   Change in fasting glucose from Baseline to 12-weeks is reported.

6. Change in Phosphocreatine Recovery [Baseline and 12-weeks]

   Change in phosphocreatine recovery, represented by ViPCr, from Baseline to 12-weeks is reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Men age 18-60 years old

2. BMI ≥ 30 kg/m2

3. Waist circumference ≥ 102 cm

4. Peak GH value of ≤ 4.2 μg/l on standard GHRH-arginine stimulation test

Exclusion Criteria:

1. Obesity due to a known secondary cause (Cushing's syndrome, hypothyroidism, etc) or a history of gastric bypass procedure.

2. Subjects who have a known history of diabetes, fasting blood sugar >125 mg/dl or using any anti-diabetic drugs.

3. Use of Aspirin, Clopidogrel (Plavix), Warfarin (Coumadin) or other anti-coagulants

4. Subjects on testosterone, glucocorticoids, anabolic steroids, GHRH, GH or IGF-1 within 3 months of enrollment.

5. Changes in lipid lowering or anti-hypertensive regimen within 3 months of screening

6. History of pituitary tumor, hypopituitarism, pituitary surgery, pituitary/brain radiation or traumatic brain injury or any other condition known to affect the GH axis.

7. Severe chronic illness including HIV, active malignancy or history of colon cancer.

8. Hemoglobin < 9.0 g/dL, SGOT > 2.5 x upper limit normal, Creatinine >1.5 mg/dL, or PSA

5 ng/ml.

1. Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit.

2. Any condition judged by the patient's physician to cause this clinical trial to be detrimental to the patient.

3. Contraindications to MRI scanning.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• Pfizer

Investigators

• Principal Investigator: Hideo Makimura, MD, PhD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hideo Makimura, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01421589
• Other Study ID Numbers: 2011-P-000770
• First Posted: Aug 23, 2011
• Last Update Posted: Jul 1, 2014
• Last Verified: May 1, 2014

• Keywords provided by Hideo Makimura, Principal Investigator, Massachusetts General Hospital: Growth hormone; GH; Obesity; Mitochondrial function; reduced growth hormone secretion
• Additional relevant MeSH terms: Obesity; Hormones

Study Results

Participant Flow

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	Growth hormone treatment: recombinant human Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.
Period Title: Overall Study
STARTED	15
COMPLETED	15
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Growth Hormone
Arm/Group Description	Growth hormone treatment: Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.
Overall Participants	15
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.9 (8.4)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	15 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 26.7%
White	10 66.7%
More than one race	0 0%
Unknown or Not Reported	1 6.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 6.7%
Not Hispanic or Latino	14 93.3%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Phosphocreatine Recovery
Description	The primary objective of this study is to determine the effects of growth hormone on mitochondrial function as assessed by 31P-MRS in obese subjects with reduced GH secretion. Mitochondrial function was represented by ViPCr, a measure of phosphocreatine recovery after sub-maximal exercise. Univariate regression analyses was performed to assess the relationship between the change in skeletal muscle IGF-1 mRNA after 12 weeks treatment with rhGH to change in ViPCr.
Time Frame	12-weeks

Outcome Measure Data

Analysis Population Description

All 15 subjects underwent 31P-MRS, however, two scans were not evaluable due to technical difficulties. In addition, paired analyses (both Baseline and 12-weeks) from only 10 subjects were available for gene expression analyses. Therefore univariate regression analyses between IGF-1 mRNA and PCr recovery could only be performed in 10 subjects.

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	Growth hormone treatment: recombinant human Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.
Measure Participants	10
Number [correlation coefficient]	0.74 (5.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments	Univariate regression analyses was performed to assess the relationship between change in skeletal muscle IGF-1 mRNA expression after 12 weeks treatment with rhGH and change in ViPCr.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Regression, Linear
	Comments

2. Secondary Outcome

Title	Change in Circulating IGF-1 Concentration
Description	Change in circulating IGF-1 from Baseline to 12-weeks is reported.
Time Frame	Baseline and 12-weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	Growth hormone treatment: recombinant human Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.
Measure Participants	15
Mean (Standard Error) [ug/l]	218 (29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Change in Skeletal Muscle IGF-1 Gene Expression
Description	Change in skeletal muscle IGF-1 gene mRNA expression from Baseline to 12-weeks is reported.
Time Frame	Baseline and 12-weeks

Outcome Measure Data

Analysis Population Description

Paired analyses (both Baseline and 12-weeks) from only 10 subjects are available for gene expression

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	Growth hormone treatment: recombinant human Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.
Measure Participants	10
Mean (Standard Error) [fold change]	2.1 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Change in Body Composition
Description	Change in waist circumference from Baseline to 12-weeks is reported.
Time Frame	Baseline and 12-weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	Growth hormone treatment: recombinant human Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.
Measure Participants	15
Mean (Standard Error) [cm]	-3 (1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Change in Inflammatory Marker
Description	Change in high sensitivity C-reactive protein (hsCRP) from Baseline to 12-weeks is reported.
Time Frame	Baseline and 12-weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	Growth hormone treatment: recombinant human Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.
Measure Participants	15
Mean (Standard Error) [mg/l]	-1.78 (0.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Change in Insulin Sensitivity
Description	Change in fasting glucose from Baseline to 12-weeks is reported.
Time Frame	Baseline and 12-weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	Growth hormone treatment: recombinant human Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.
Measure Participants	15
Mean (Standard Error) [mg/dl]	6 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Change in Phosphocreatine Recovery
Description	Change in phosphocreatine recovery, represented by ViPCr, from Baseline to 12-weeks is reported.
Time Frame	Baseline and 12-weeks

Outcome Measure Data

Analysis Population Description

Obese men with reduced GH secretion were treated with rhGH for 12 weeks. All 15 subjects underwent 31P-MRS, however, two scans were not evaluable due to technical difficulties.

Arm/Group Title	Growth Hormone
Arm/Group Description	Growth hormone treatment: recombinant human Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.
Measure Participants	13
Mean (Standard Error) [mM/min]	-10.2 (7.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Growth Hormone Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Growth Hormone Treatment
Arm/Group Description	Growth hormone treatment: recombinant human Growth hormone 0.4 mg once daily (titrated to IGF-1) by sub-cutaneous injection for 12 weeks.
All Cause Mortality
	Growth Hormone Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Growth Hormone Treatment
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	Growth Hormone Treatment
	Affected / at Risk (%)	# Events
Total	11/15 (73.3%)
Cardiac disorders
Peripheral edema	4/15 (26.7%)
Immune system disorders
Hypersensitivity reaction	0/15 (0%)
Metabolism and nutrition disorders
Diabetes	0/15 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/15 (26.7%)
Carpal tunnel syndrome	0/15 (0%)
Myalgias	5/15 (33.3%)
Nervous system disorders
Head ache	2/15 (13.3%)
Paresthesias	1/15 (6.7%)
Skin and subcutaneous tissue disorders
Injection site bleeding	1/15 (6.7%)
Injection site bruising	5/15 (33.3%)
Injection site pain, pruritis, erythema, induration	0/15 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.