Study of Growth Hormone and Bone in Obesity

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01724489
• Collaborator: National Institutes of Health (NIH) (NIH), Pfizer (Industry)
• Enrollment: 77
• Location: 1
• Arms: 2
• Duration (Months): 68
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

Obesity is an important risk factor for osteoporosis and fractures. With the growing prevalence of obesity in the U.S., understanding the pathophysiology of bone loss in this population is of importance to public health. Growth hormone (GH) is a critical mediator of bone homeostasis and is markedly reduced in obesity. Our preliminary data suggest an important role for the GH/insulin-like growth factor 1 (IGF-1) system in the pathogenesis of bone loss in obesity. The development of novel imaging techniques provides an opportunity to investigate the effects of GH on skeletal structure and strength, which will provide insights into the pathogenesis of obesity related bone loss. Understanding the pathophysiology of bone loss in obesity may help identify new treatment targets for this important complication. The investigator hypothesizes that low-dose GH administration for 18 months will improve skeletal health.

Condition or Disease	Intervention/Treatment	Phase
Obesity; Osteopenia	Drug: Growth hormone; Drug: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Skeletal Physiology Dysregulation in Obesity: The Role of Growth Hormone
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Nov 15, 2018
• Actual Study Completion Date: Apr 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Growth Hormone Growth Hormone is Genotropin, provided by Pfizer Inc. It is self administered daily for 18 months using a 5 mg injection pen device. Dose will be titrated based on IGF-1 levels.	Drug: Growth hormone; Other Names: Genotropin (Pfizer Inc.)
Placebo Comparator: Placebo Placebo will be provided by Pfizer Inc. It will appear identical to active growth hormone and will be administered in the same manner.	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Bone Mineral Density [baseline and 18 months]

   Change in BMD over 18 months in the GH vs placebo group

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Ages 18-65 and generally healthy

• BMI ≥ 25 kg/m2

• Bone mineral density (BMD) T score ≤ -1.0 and > -2.5 (as measured by DXA)

Exclusion Criteria:

• For women: amenorrhea for 3 months, pregnancy or breastfeeding, polycystic ovary syndrome

• History of diabetes mellitus, cancer or other serious chronic disease

• Use of osteoporosis medications

• Anemia

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
• National Institutes of Health (NIH)
• Pfizer

Investigators

• Principal Investigator: Karen Miller, MD, Massachusetts General Hospital
• Principal Investigator: Miriam Bredella, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol - Nov 7, 2019
• Statistical Analysis Plan - Nov 7, 2019

More Information

Publications

None provided.

• Responsible Party: Karen Klahr Miller, MD, Chief, Neuroendocrine Unit, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01724489
• Other Study ID Numbers: 2012P002276
• First Posted: Nov 9, 2012
• Last Update Posted: Dec 17, 2019
• Last Verified: Dec 1, 2019

• Additional relevant MeSH terms: Bone Diseases, Metabolic; Obesity; Hormones

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from August 2013 to April 2017. Recruitment techniques included posting advertisements on the internet (i.e. Facebook and Craigslist) and on the Massachusetts General Hospital's clinical trial recruitment website.
Pre-assignment Detail	Of the 253 people who signed a consent form, 165 were unable to participate due to various reasons including meeting ineligibility criteria. The 88 subjects remaining were randomized to one of two arms. Of these 88 subjects, a total of 77 subjects had baseline measurements collected.

Arm/Group Title	Growth Hormone	Placebo
Arm/Group Description	Growth Hormone (GH) is Genotropin, provided by Pfizer Inc. It is a self-administered sub-cutaneous daily injection using an injection pen device. It was administered up to 18 months. The dose was titrated based on IGF-1 hormone levels with the goal of maintaining an IGF-1 level in the upper-quartile of the normal range.	Placebo was provided by Pfizer Inc. It appeared identical to active growth hormone and was administered in the same manner; self administered sub-cutaneous daily for 18 months using an injection pen device. Dose was titrated in a way to maintain the double-blind.
Period Title: Overall Study
STARTED	39	38
COMPLETED	23	26
NOT COMPLETED	16	12

Baseline Characteristics

Arm/Group Title	Growth Hormone	Placebo	Total
Arm/Group Description	Growth Hormone is Genotropin, provided by Pfizer Inc. It is self administered daily for 18 months using a 5 mg injection pen device. Dose will be titrated based on IGF-1 levels. Growth hormone	Placebo will be provided by Pfizer Inc. It will appear identical to active growth hormone and will be administered in the same manner. Placebo	Total of all reporting groups
Overall Participants	39	38	77
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47 (13)	49 (12)	48 (12)
Sex: Female, Male (Count of Participants)
Female	18 46.2%	18 47.4%	36 46.8%
Male	21 53.8%	20 52.6%	41 53.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 5.1%	4 10.5%	6 7.8%
Not Hispanic or Latino	37 94.9%	34 89.5%	71 92.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 10.3%	1 2.6%	5 6.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 15.4%	7 18.4%	13 16.9%
White	27 69.2%	30 78.9%	57 74%
More than one race	2 5.1%	0 0%	2 2.6%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Bone Mineral Density
Description	Change in BMD over 18 months in the GH vs placebo group
Time Frame	baseline and 18 months

Outcome Measure Data

Analysis Population Description

Two subjects from the growth hormone arm were not analyzed due to large amount of weight loss, which has a well-documented effect of decreasing BMD. AP spine bone density in one study subject in the placebo group was excluded because the scan was technically poor. These data were excluded before the study was unblinded.

Arm/Group Title	Growth Hormone	Placebo
Arm/Group Description	Growth Hormone (GH) is Genotropin, provided by Pfizer Inc. It is a self-administered sub-cutaneous daily injection using an injection pen device. It was administered up to 18 months. The dose was titrated based on IGF-1 hormone levels with the goal of maintaining an IGF-1 level in the upper-quartile of the normal range.	Placebo was provided by Pfizer Inc. It appeared identical to active growth hormone and was administered in the same manner; self administered sub-cutaneous daily for 18 months using an injection pen device. Dose was titrated in a way to maintain the double-blind.
Measure Participants	21	25
Mean (Standard Deviation) [grams/cm^2]	-0.015 (0.033)	-0.008 (0.034)

Adverse Events

Time Frame	18 months
Adverse Event Reporting Description	Growth hormone (Pfizer) is FDA approved and has a possible side-effect profile described/listed in the medication package insert. The investigators recorded all adverse events (as defined by the clinicaltrials.gov definition) and categorized them by "expected" (eg listed in the medication package insert) and "unexpected" (not listed in the medication package insert). # of events = # of subjects that experienced the side effect at any point during the study.
Arm/Group Title	Growth Hormone		Placebo
Arm/Group Description	Growth Hormone is Genotropin, provided by Pfizer Inc. It is self administered daily for 18 months using a 5 mg injection pen device. Dose will be titrated based on IGF-1 levels. Growth hormone		Placebo will be provided by Pfizer Inc. It will appear identical to active growth hormone and will be administered in the same manner. Placebo
All Cause Mortality
	Growth Hormone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/38 (0%)
Serious Adverse Events
	Growth Hormone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		1/38 (2.6%)
Psychiatric disorders
prolonged inpatient psychiatric hospitalization	0/39 (0%)	0	1/38 (2.6%)	1
Other (Not Including Serious) Adverse Events
	Growth Hormone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/39 (74.4%)		13/38 (34.2%)
Blood and lymphatic system disorders
edema (swelling) in the hands and/or feet	8/39 (20.5%)	11	6/38 (15.8%)	6
General disorders
headache	1/39 (2.6%)	1	2/38 (5.3%)	3
Metabolism and nutrition disorders
elevated blood sugar	5/39 (12.8%)	5	2/38 (5.3%)	2
Musculoskeletal and connective tissue disorders
pain and/or stiffness in the hands and/or feet	9/39 (23.1%)	10	1/38 (2.6%)	1
joint pain	5/39 (12.8%)	5	1/38 (2.6%)	1
myalgia (muscle aches)	7/39 (17.9%)	7	3/38 (7.9%)	3
carpal tunnel syndrome	1/39 (2.6%)	1	0/38 (0%)	0
joint stiffness (not in the hands and/or feet)	2/39 (5.1%)	2	0/38 (0%)	0
Nervous system disorders
tingling	13/39 (33.3%)	16	3/38 (7.9%)	4
Skin and subcutaneous tissue disorders
injection site discomfort	2/39 (5.1%)	2	1/38 (2.6%)	1
injection site bruising	0/39 (0%)	0	1/38 (2.6%)	1

Limitations/Caveats

Study medication was discontinued at 18 months. Subjects were followed for an additional 6 months off of study medication. The data reported here are for the primary 18-month trial.

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.