Obesity
Conditions
Keywords
Visceral obesity, Growth hormone, Cardiovascular risk, Insulin resistance
Brief summary
This study will compare growth hormone levels and cardiovascular risk markers in normal weight and overweight women and men. In women and men with increased abdominal weight, growth hormone (GH) versus placebo will be administered and effects on cardiovascular risk, insulin resistance and body composition will be measured.
Detailed description
The purpose of this study is to measure growth hormone levels in women and men who are normal weight, overweight, and obese. Growth hormone levels will be correlated with body weight, body composition, and markers of cardiovascular risk. In overweight or obese women and men with increased visceral adiposity and below average IGF-1 levels, growth hormone versus placebo will be given for 6 months. Effects of growth hormone treatment on weight, body composition, insulin resistance, lipids, and cardiovascular risk markers will then be assessed. Study subjects will be followed for an additional six months for these endpoints.
Interventions
DRUGNutropin AQ growth hormone
Participants will give themselves injections of growth hormone every night for 6 months.
Participants will give themselves injections of placebo growth hormone every night for 6 months.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* For growth hormone measurement part (for men and women): 1. For visceral adiposity arm: waist circumference greater than or equal to 88 cm for women or 102 cm for men, and BMI greater than or equal to 25 kg/m2 2. For lean controls: BMI 18.5 to 24.9 kg/m2 * For growth hormone treatment part (for men and women): 1. Visceral adiposity (waist circumference greater than or equal to 88 cm for women and 102 for men, BMI greater than or equal to 25 kg/m2) 2. IGF-I within the lowest 2 quartiles for age and gender 3. Willingness to maintain current activity level and diet
Exclusion criteria
* Diabetes mellitus (fasting plasma glucose greater than 126 mg/dL or 2-hour post-oral glucose tolerance test \[OGTT\] plasma glucose greater than 200) * Taking the following medications in the last 3 months: weight loss or lipid-lowering agents, medications to treat diabetes mellitus or pre-diabetes, oral contraceptives or estrogen-containing medications, other medications known to significantly affect weight * Smoking * Hematocrit below the lower limit of normal * Amenorrhea for 3 months (in women) * Pregnant or breastfeeding (in women) * Polycystic ovary syndrome (in women) * Weight that exceeds 280 pounds * SGPT greater than 2 times the upper limit of normal * History of malignancy, except for fully resolved basal cell carcinomas of the skin (Specific Aim 2 only) * Radiation exposure greater than 1000 mrem over the last 12 months * Previous diagnosis of cardiovascular disease * History of pituitary or hypothalamic disease, brain radiation, or childhood growth hormone deficiency * History of carpal tunnel syndrome that has not been surgically treated
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Abdominal Fat | Measured at baseline and month 6 | 6 month change in visceral abdominal fat (primary body composition endpoint) |
| Total Abdominal Fat | Measured at baseline and month 6 | 6 month change in total abdominal fat (primary body composition endpoint) |
| HsCRP | Measured at baseline and month 6 | 6 month change in HsCRP (primary cardiovascular risk endpoint) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure of Insulin Resistance | Measured at baseline and month 6 | 6 month change in 2-hour glucose (primary insulin resistance endpoint) |
| Insulin-like Growth Factor-1 (IGF-1) Levels | Measured at baseline and month 6 | 6-month change in IGF-1 levels |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Female on GH Participants received growth hormone replacement therapy. The starting dose was 4 micrograms/kg per day and they were titrated within the normal range based on blood levels.
Nutropin AQ growth hormone : Participants gave themselves injections of growth hormone every night for 6 months. | 40 |
| Female on Placebo Participants received placebo.
Placebo Growth Hormone : Participants gave themselves injections of placebo every night for 6 months. | 40 |
| Male on GH Participants received growth hormone replacement therapy. The starting dose was 2 micrograms/kg per day and they were titrated within the normal range based on blood levels.
Nutropin AQ growth hormone : Participants gave themselves injections of growth hormone every night for 6 months. | 32 |
| Male on Placebo Participants received placebo.
Placebo Growth Hormone : Participants gave themselves injections of placebo every night for 6 months. | 30 |
| Total | 142 |
Baseline characteristics
| Characteristic | Female on Placebo | Male on GH | Female on GH | Male on Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 32 Participants | 40 Participants | 30 Participants | 142 Participants |
| Age, Continuous | 36.1 years STANDARD_DEVIATION 1.1 | 32.4 years STANDARD_DEVIATION 1.2 | 35.7 years STANDARD_DEVIATION 1.1 | 34.3 years STANDARD_DEVIATION 1.1 | 34.6 years STANDARD_DEVIATION 1.13 |
| Region of Enrollment United States | 40 participants | 32 participants | 40 participants | 30 participants | 142 participants |
| Sex: Female, Male Female | 40 Participants | 0 Participants | 40 Participants | 0 Participants | 80 Participants |
| Sex: Female, Male Male | 0 Participants | 32 Participants | 0 Participants | 30 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 40 | 3 / 40 | 7 / 32 | 3 / 30 |
| serious Total, serious adverse events | 0 / 40 | 1 / 40 | 0 / 32 | 1 / 30 |
Outcome results
Primary
Abdominal Fat
6 month change in visceral abdominal fat (primary body composition endpoint)
Time frame: Measured at baseline and month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Male on GH | Abdominal Fat | -15.9 cm^2 | Standard Error 6.3 |
| Male on Placebo | Abdominal Fat | -0.2 cm^2 | Standard Error 7.2 |
Primary
HsCRP
6 month change in HsCRP (primary cardiovascular risk endpoint)
Time frame: Measured at baseline and month 6
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Male on GH | HsCRP | -1.1 mg/L | Standard Error 0.5 |
| Male on Placebo | HsCRP | 0.5 mg/L | Standard Error 0.3 |
| Female on GH | HsCRP | -1.3 mg/L | Standard Error 0.2 |
| Female on Placebo | HsCRP | -0.3 mg/L | Standard Error 0.2 |
Primary
Total Abdominal Fat
6 month change in total abdominal fat (primary body composition endpoint)
Time frame: Measured at baseline and month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Male on GH | Total Abdominal Fat | -28.0 cm^2 | Standard Error 9.7 |
| Male on Placebo | Total Abdominal Fat | 1.5 cm^2 | Standard Error 11 |
Secondary
Insulin-like Growth Factor-1 (IGF-1) Levels
6-month change in IGF-1 levels
Time frame: Measured at baseline and month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Male on GH | Insulin-like Growth Factor-1 (IGF-1) Levels | 179.0 ng/mL | Standard Error 31.5 |
| Male on Placebo | Insulin-like Growth Factor-1 (IGF-1) Levels | 9.9 ng/mL | Standard Error 7.8 |
| Female on GH | Insulin-like Growth Factor-1 (IGF-1) Levels | 106.5 ng/mL | Standard Error 17.5 |
| Female on Placebo | Insulin-like Growth Factor-1 (IGF-1) Levels | -20.8 ng/mL | Standard Error 7.6 |
Secondary
Measure of Insulin Resistance
6 month change in 2-hour glucose (primary insulin resistance endpoint)
Time frame: Measured at baseline and month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Male on GH | Measure of Insulin Resistance | 5.3 mg/dL | Standard Error 5.6 |
| Male on Placebo | Measure of Insulin Resistance | -12.5 mg/dL | Standard Error 5.8 |
| Female on GH | Measure of Insulin Resistance | 18.6 mg/dL | Standard Error 6.3 |
| Female on Placebo | Measure of Insulin Resistance | -0.9 mg/dL | Standard Error 8.2 |