Effect of Recombinant Human Growth Hormone (rhGH) on Abdominal Fat and Cardiovascular Risk in Obese Girls

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01169103
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 22
• Location: 1
• Arms: 2
• Duration (Months): 57
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Teenagers and adults who are overweight or obese have an increase in fat in the abdomen, which increases their risk for diabetes and heart disease. Reducing abdominal fat is important to reduce risk for diabetes and for heart disease. Overweight teenagers also have low levels of growth hormone compared to normal weight teenagers, and teenagers with the lowest growth hormone levels also have the greatest abdominal fat. In children who are unable to make growth hormone for other reasons, giving back growth hormone leads to a decrease in abdominal fat. We are studying whether giving growth hormone in small doses to overweight teenagers can change body composition. We hypothesize that growth hormone will cause abdominal fat to decrease and reduce the risk markers for diabetes and heart disease.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: recombinant human growth hormone (rhGH); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Effect of rhGH Administration on Visceral Adiposity and Markers of Cardiovascular Risk in Obese Adolescent Girls: Phase 2
• Study Start Date: Mar 1, 2010
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: recombinant human growth hormone Forty subjects will be randomized to receive either recombinant human growth hormone or placebo.	Drug: recombinant human growth hormone (rhGH); Initial rhGH dose 0.4mg administered by subcutaneous injection daily. Dose will be increased to 0.6 mg after one week and then increased to 0.8mg after two weeks.
Placebo Comparator: Placebo Forty subjects will be randomized to receive either recombinant human growth hormone or placebo.	Drug: Placebo; Placebo will be administered by daily subcutaneous injections. Sham increases will be used.

Outcome Measures

Primary Outcome Measures

1. Change in Visceral and Subcutaneous Abdominal Adipose Tissue Over 6 Months [Baseline and 6 months]

   Visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAT) were assessed using single slice MR imaging (MRI)

2. Changes in Lipid Panel [Baseline and 6 months]

   Lipid profile will be obtained using established methods. Total Cholesterol, Triglycerides, LDL and HDL measurements will be obtained at baseline, and then at the six-month visits to determine the rate at which lipid measures change with rhGH therapy

3. Change in High-sensitivity C-reactive Protein (Hs-CRP) Over 6 Months [Baseline and 6 months]

   As a marker of cardiovascular risk, hs-CRP will be assessed at baseline and 6 months to assess the rate at which hs-CRP levels change with rhGH therapy.

4. Change in Soluble Intercellular Adhesion Molecule-1 (sICAM) Over 6 Months [Baseline and 6 months]

   Soluble intercellular adhesion molecule-1 (sICAM) was used as a surrogate marker of cardiovascular risk

Secondary Outcome Measures

1. Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Score [Baseline and 6 months]

   Homeostasis model assessment of insulin resistance (HOMA-IR) was used as a validated measure of insulin resistance. A 2-hour Oral Glucose Tolerance Test (OGTT) using 1.75 gram/kilogram of oral glucose (maximum 75 gram) will be performed at baseline and six months after administration of rhGH/placebo/ no therapy. Fasting insulin and glucose will be used to determine HOMA-IR: [fasting glucose (mmol/l) x fasting insulin (µU/ml)]/22.5]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years to 21 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adolescent girls 13-21 years old with bone age ≥ 14 years

• Overweight girls: Body Mass Index (BMI) greater than the 95th percentile for age

• Waist/Hip ratio ≥ 0.85

• Insulin Like Growth Factor -1 (IGF-1) below -0.5 standard deviations (SD) for pubertal stage or age

Exclusion Criteria:

• Pregnancy (positive pregnancy test) prior to enrollment in the study

• Significant weight gain or loss within 3 months of study (more than 5 kg)

• Use of medications that affect GH or cortisol levels (such as estrogen including oral contraceptive pills, oral glucocorticoids)

• Use of medications such as Meridian and Orlistat

• Presence of diabetes mellitus

• Uncontrolled Thyroid disorders

• Chronic renal insufficiency

• Participation in another simultaneous medical investigation or trial

• Active neoplasm or history of cancer

• Prader-Willi syndrome

• History of scoliosis if bone age is <15 years

• Hypersensitivity to rhGH or constituents of the injections

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
• Genentech, Inc.

Investigators

• Principal Investigator: Madhusmita Misra, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Madhusmita Misra, Associate Professor of Pediatrics, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01169103
• Other Study ID Numbers: 2009P000861
• First Posted: Jul 23, 2010
• Last Update Posted: Nov 2, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Madhusmita Misra, Associate Professor of Pediatrics, Massachusetts General Hospital: Obesity; Adolescent; Insulin resistance; Growth hormone; Visceral fat; Adolescent obesity
• Additional relevant MeSH terms: Obesity; Hormones

Study Results

Participant Flow

Recruitment Details	Participants were recruited at Massachusetts General Hospital between September 2010 and October 2012 through area pediatric and obesity clinics and advertisements.
Pre-assignment Detail	Of the 32 subjects who were screened, 22 were eligible & randomized. 5 subjects were ineligible due to Insulin Like Growth Factor levels above the eligibility limit for pubertal stage or age. 2 were excluded due to planned initiation of medications that were on the exclusion criteria list and 3 voluntarily withdrew consent prior to randomization.

Arm/Group Title	Recombinant Human Growth Hormone	Placebo/no Treatment
Arm/Group Description	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo/no treatment. recombinant human growth hormone (rhGH) : Initial rhGH dose 0.4mg administered by subcutaneous injection daily. Dose will be increased to 0.6 mg after one week and then increased to 0.8mg after two weeks.	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo. Placebo : Placebo will be administered by daily subcutaneous injections. Sham increases will be used. Due to expiration of placebo medication, placebo subjects who enrolled after 6/2012 were randomized to no treatment.
Period Title: Overall Study
STARTED	11	11
COMPLETED	5	7
NOT COMPLETED	6	4

Baseline Characteristics

Arm/Group Title	Recombinant Human Growth Hormone	Placebo/no Treatment	Total
Arm/Group Description	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo/no treatment. recombinant human growth hormone (rhGH) : Initial rhGH dose 0.4mg administered by subcutaneous injection daily. Dose will be increased to 0.6 mg after one week and then increased to 0.8mg after two weeks.	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo. Placebo : Placebo will be administered by daily subcutaneous injections. Sham increases will be used. Due to expiration of placebo medication, placebo subjects who enrolled after 6/2012 were randomized to no treatment.	Total of all reporting groups
Overall Participants	11	11	22
Age (Count of Participants)
<=18 years	9 81.8%	8 72.7%	17 77.3%
Between 18 and 65 years	2 18.2%	3 27.3%	5 22.7%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	16.2 (2.6)	16.9 (2.1)	16.6 (2.34)
Sex: Female, Male (Count of Participants)
Female	11 100%	11 100%	22 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	11 100%	11 100%	22 100%

Outcome Measures

1. Primary Outcome

Title	Change in Visceral and Subcutaneous Abdominal Adipose Tissue Over 6 Months
Description	Visceral adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAT) were assessed using single slice MR imaging (MRI)
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

Due to scheduling difficulties one no treatment subject did not perform the MRI portion of the study at either the baseline or the 6 month visit.

Arm/Group Title	Recombinant Human Growth Hormone	Placebo/no Treatment
Arm/Group Description	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo/no treatment. recombinant human growth hormone (rhGH) : Initial rhGH dose 0.4mg administered by subcutaneous injection daily. Dose will be increased to 0.6 mg after one week and then increased to 0.8mg after two weeks.	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo. Placebo : Placebo will be administered by daily subcutaneous injections. Sham increases will be used. Due to expiration of placebo medication, placebo subjects who enrolled after 6/2012 were randomized to no treatment.
Measure Participants	5	6
Change in VAT	57 (2993)	799 (3184)
Change in SAT	-111 (6078)	3634 (5161)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Recombinant Human Growth Hormone, Placebo/no Treatment
	Comments	We assumed that mean decrease in visceral fat in our population would be 0.85*standard deviation score (SDS). Therefore, 18 subjects in each group would be required in order for us to have an 81.7% chance of detecting a significant difference in the mean 6-month changes in visceral adiposity between the groups at a 5% significance level by rejecting the null hypothesis that there is no difference in change in visceral fat following administration of rhGH or placebo in obese adolescent girls.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Recombinant Human Growth Hormone, Placebo/no Treatment
	Comments	Change in SAT p-value
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Score
Description	Homeostasis model assessment of insulin resistance (HOMA-IR) was used as a validated measure of insulin resistance. A 2-hour Oral Glucose Tolerance Test (OGTT) using 1.75 gram/kilogram of oral glucose (maximum 75 gram) will be performed at baseline and six months after administration of rhGH/placebo/ no therapy. Fasting insulin and glucose will be used to determine HOMA-IR: [fasting glucose (mmol/l) x fasting insulin (µU/ml)]/22.5]
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Recombinant Human Growth Hormone	Placebo/no Treatment
Arm/Group Description	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo/no treatment. recombinant human growth hormone (rhGH) : Initial rhGH dose 0.4mg administered by subcutaneous injection daily. Dose will be increased to 0.6 mg after one week and then increased to 0.8mg after two weeks.	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo. Placebo : Placebo will be administered by daily subcutaneous injections. Sham increases will be used. Due to expiration of placebo medication, placebo subjects who enrolled after 6/2012 were randomized to no treatment.
Measure Participants	5	7
Mean (Standard Deviation) [HOMA-IR score]	-0.52 (2.63)	-2.92 (8.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Recombinant Human Growth Hormone, Placebo/no Treatment
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Primary Outcome

Title	Changes in Lipid Panel
Description	Lipid profile will be obtained using established methods. Total Cholesterol, Triglycerides, LDL and HDL measurements will be obtained at baseline, and then at the six-month visits to determine the rate at which lipid measures change with rhGH therapy
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Recombinant Human Growth Hormone	Placebo/no Treatment
Arm/Group Description	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo/no treatment. recombinant human growth hormone (rhGH) : Initial rhGH dose 0.4mg administered by subcutaneous injection daily. Dose will be increased to 0.6 mg after one week and then increased to 0.8mg after two weeks.	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo. Placebo : Placebo will be administered by daily subcutaneous injections. Sham increases will be used. Due to expiration of placebo medication, placebo subjects who enrolled after 6/2012 were randomized to no treatment.
Measure Participants	5	7
Change in Total Cholesterol	-37.8 (23.9)	-8.6 (15.5)
Change in Triglycerides	-27.8 (46.8)	6.1 (58.4)
Change in LDL	-25.8 (12.8)	-10.7 (11.9)
Change in HDL	-6.6 (6.1)	1 (5.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Recombinant Human Growth Hormone, Placebo/no Treatment
	Comments	Change in Total Cholesterol p-value
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Recombinant Human Growth Hormone, Placebo/no Treatment
	Comments	Change in Triglyceride p-value
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Recombinant Human Growth Hormone, Placebo/no Treatment
	Comments	Change in Low-density lipoprotein p-value
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.062
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Recombinant Human Growth Hormone, Placebo/no Treatment
	Comments	Change in High-density lipoprotein p-value
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0396
	Comments
	Method	t-test, 2 sided
	Comments

4. Primary Outcome

Title	Change in High-sensitivity C-reactive Protein (Hs-CRP) Over 6 Months
Description	As a marker of cardiovascular risk, hs-CRP will be assessed at baseline and 6 months to assess the rate at which hs-CRP levels change with rhGH therapy.
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Recombinant Human Growth Hormone	Placebo/no Treatment
Arm/Group Description	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo/no treatment. recombinant human growth hormone (rhGH) : Initial rhGH dose 0.4mg administered by subcutaneous injection daily. Dose will be increased to 0.6 mg after one week and then increased to 0.8mg after two weeks.	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo. Placebo : Placebo will be administered by daily subcutaneous injections. Sham increases will be used. Due to expiration of placebo medication, placebo subjects who enrolled after 6/2012 were randomized to no treatment.
Measure Participants	5	7
Mean (Standard Deviation) [mg/L]	-0.77 (2.4)	-0.09 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Recombinant Human Growth Hormone, Placebo/no Treatment
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.58
	Comments
	Method	t-test, 2 sided
	Comments

5. Primary Outcome

Title	Change in Soluble Intercellular Adhesion Molecule-1 (sICAM) Over 6 Months
Description	Soluble intercellular adhesion molecule-1 (sICAM) was used as a surrogate marker of cardiovascular risk
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Recombinant Human Growth Hormone	Placebo/no Treatment
Arm/Group Description	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo/no treatment. recombinant human growth hormone (rhGH) : Initial rhGH dose 0.4mg administered by subcutaneous injection daily. Dose will be increased to 0.6 mg after one week and then increased to 0.8mg after two weeks.	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo. Placebo : Placebo will be administered by daily subcutaneous injections. Sham increases will be used. Due to expiration of placebo medication, placebo subjects who enrolled after 6/2012 were randomized to no treatment.
Measure Participants	5	7
Mean (Standard Deviation) [ng/mL]	-22.2 (30.3)	21.1 (33.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Recombinant Human Growth Hormone, Placebo/no Treatment
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Arm/Group Title	Recombinant Human Growth Hormone		Placebo/no Treatment
Arm/Group Description	Forty subjects will be randomized to receive either recombinant human growth hormone or placebo/no treatment. recombinant human growth hormone (rhGH) : Initial rhGH dose 0.4mg administered by subcutaneous injection daily. Dose will be increased to 0.6 mg after one week and then increased to 0.8mg after two weeks.		Forty subjects will be randomized to receive either recombinant human growth hormone or placebo. Placebo : Placebo will be administered by daily subcutaneous injections. Sham increases will be used. Due to expiration of placebo medication, placebo subjects who enrolled after 6/2012 were randomized to no treatment.
All Cause Mortality
	Recombinant Human Growth Hormone		Placebo/no Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Recombinant Human Growth Hormone		Placebo/no Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	Recombinant Human Growth Hormone		Placebo/no Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/11 (90.9%)		7/11 (63.6%)
Cardiac disorders
Hypertension	0/11 (0%)		1/11 (9.1%)
Endocrine disorders
Impaired Glucose Tolerance	2/11 (18.2%)		4/11 (36.4%)
Polyuria/Polydipsia	1/11 (9.1%)		3/11 (27.3%)
HbA1c > 6.4%	1/11 (9.1%)		0/11 (0%)
Change in Menstrual Flow	3/11 (27.3%)		2/11 (18.2%)
Fatigue	0/11 (0%)		2/11 (18.2%)
Eye disorders
Blurry Vision	1/11 (9.1%)		0/11 (0%)
Gastrointestinal disorders
Nausea with vomiting	1/11 (9.1%)		0/11 (0%)
Nausea without vomiting	3/11 (27.3%)		0/11 (0%)
Abdominal Pain	2/11 (18.2%)		0/11 (0%)
General disorders
Headache	4/11 (36.4%)		3/11 (27.3%)
Dizziness without Headace	0/11 (0%)		1/11 (9.1%)
ED visit for wheezing with URI	0/11 (0%)		1/11 (9.1%)
Eczema	0/11 (0%)		1/11 (9.1%)
Infections and infestations
Upper Respiratory Infection	1/11 (9.1%)		0/11 (0%)
Nasal Congestion	1/11 (9.1%)		0/11 (0%)
Injury, poisoning and procedural complications
Bruising/Irritation at Injection Site	2/11 (18.2%)		2/11 (18.2%)
Bruising/Irritation at Blood Sampling Site	1/11 (9.1%)		0/11 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/11 (18.2%)		0/11 (0%)
Back Pain	4/11 (36.4%)		1/11 (9.1%)
Myalgia	1/11 (9.1%)		0/11 (0%)

Limitations/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.