Obesity, Osteopenia
Conditions
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.
Interventions
DRUGGrowth hormone
DRUGPlacebo
Sponsors
National Institutes of Health (NIH)
Pfizer
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Mineral Density | baseline and 18 months | Change in BMD over 18 months in the GH vs placebo group |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Growth hormone | 39 |
| Placebo Placebo will be provided by Pfizer Inc. It will appear identical to active growth hormone and will be administered in the same manner.
Placebo | 38 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 3 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Surgery, medication | 1 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 6 |
Baseline characteristics
| Characteristic | Placebo | Total | Growth Hormone |
|---|---|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 12 | 48 years STANDARD_DEVIATION 12 | 47 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 71 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 13 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 57 Participants | 27 Participants |
| Sex: Female, Male Female | 18 Participants | 36 Participants | 18 Participants |
| Sex: Female, Male Male | 20 Participants | 41 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 38 |
| other Total, other adverse events | 29 / 39 | 13 / 38 |
| serious Total, serious adverse events | 0 / 39 | 1 / 38 |
Outcome results
Primary
Bone Mineral Density
Change in BMD over 18 months in the GH vs placebo group
Time frame: baseline and 18 months
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Growth Hormone | Bone Mineral Density | -0.015 grams/cm^2 | Standard Deviation 0.033 |
| Placebo | Bone Mineral Density | -0.008 grams/cm^2 | Standard Deviation 0.034 |