AIDS, HIV Infections
Conditions
Keywords
HIV, lipodystrophy, growth hormone, visceral fat, IGF-I, Treatment Experienced
Brief summary
This study will investigate long-term, low-dose growth hormone administration in HIV-infected patients with reduced growth hormone (GH) secretion and increased visceral adiposity. We hypothesize that low-dose growth hormone will reduce visceral fat. Secondary endpoints will include measures of insulin-like growth factor-1 (IGF-1), glucose homeostasis, lipids, blood pressure,bone density, cardiovascular risk and safety parameters.
Detailed description
This study will investigate long-term, low-dose growth hormone administration in HIV-infected patients with reduced growth hormone (GH) secretion and increased visceral adiposity. We hypothesize that low-dose growth hormone will reduce visceral fat preferentially over subcutaneous fat, and increase lean body mass. Secondary endpoints will include measures of IGF-1, glucose homeostasis, lipids, blood pressure,bone density, cardiovascular risk and safety parameters. Dosing of growth hormone will be based on patients' IGF-1 levels and will not exceed 6mcg/kg/day.
Interventions
DRUGrecombinant human growth hormone
growth hormone dosed by weight and IGF-1 level,subcutaneously once a day, 18 months
DRUGplacebo
placebo subcutaneously once a day, 18 months
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Men and women age 18-60 * Previously diagnosed HIV infection * Stable antiviral regimen for at least 12 weeks prior to enrollment * Waist-to-hip ratio \>0.90 for men and \>0.85 for women * Evidence of at least one of the following recent changes: \*increased abdominal girth, \*relative loss of fat in the extremities, \*relative loss of fat in the face * Simulated peak GH response to arginine/GHRH of less than 7.5 mcg/dL
Exclusion criteria
* Use of Megace, anti-diabetic agents, GH, or other anabolic agents, pharmacologic glucocorticoid (prednisone \>5 mg/day or its equivalent) for 3 months prior to enrollment. Patients on a standard dose of testosterone for documented hypogonadism will be allowed to enter the protocol. Women taking standard estrogen replacement therapy for \>3 months will be allowed in the study. * Diabetes mellitus * Other severe chronic illness * HgB \<9.0 g/dL, creatinine \>1.4 mg/dL, or PSA \>4 ng/mL * Positive BHCG or failure to use appropriate birth control during study. Acceptable methods include oral contraceptives, depo provera or combined progesterone-estrogen injections, transdermal contraceptive patches, IUD's, barrier devices (condoms, diaphragms), and abstinence. * Carpal tunnel syndrome * Active malignancy or history of pituitary malignancy, history of colon cancer or prostate malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visceral Adipose Tissue Area From Baseline to 18 Months | 18 months | change in visceral adipose tissue area as measured by single-slice abdominal computed tomographic scan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Trunk Fat | 18 months | — |
| Change in Fasting Glucose | 18 months | change in fasting glucose |
| Change in Trunk to Extremity Ratio | 18 months | change in trunk to extremity ratio |
| Change in Triglycerides | 18 months | Change in triglycerides |
| Change in Subcutaneous Adipose Tissue | 18 months | Change in subcutaneous adipose tissue |
| Change in CD4 Cells | 18 months | Change in CD4 cells |
| Change in Logarithm HIV Viral Load | 18 months | Change in logarithm base 10 HIV viral load |
| Change in Lean Body Mass | 18 months | change in lean body mass |
| Change in Insulin-like Growth Factor-I From Baseline to 18 Months | 18 months | Change in insulin-like growth factor-1 |
| Change in Diastolic Blood Pressure | 18 months | Change in diastolic blood pressure |
| Change in Adiponectin | 18 months | Change in adiponectin |
| Change in Carotid Intima Media Thickness (IMT) | 18 months | change in carotid intima media thickness (IMT) |
| Change in Body Mass Index | 18 months | Change in body mass index |
| Change in Extremity Fat | 18 months | Change in extremity fat |
| Change in 2-hour Glucose | 18 months | Change in 2-hour glucose |
| Change in Systolic Blood Pressure | 18 months | Change in systolic blood pressure |
| Change in Quality of Life Score From the Medical Outcomes Study-HIV Survey From Baseline to 18 Months | 18 months | Change in quality of life score was measured by the Medical Outcomes Study-HIV (MOS-HIV)survey. The MOS-HIV asks patients to report on health-related quality of life and physical function from the past 4 days. The scoring range is 0-100, and a higher score indicates better quality of life. |
Countries
United States
Participant flow
Recruitment details
Patients with HIV and lipodystrophy were recruited between November 2003 and March 2006 via community advertisement, HIV support and advocacy groups, and infectious disease or primary care physician referral.
Pre-assignment details
Patients who do not meet growth hormone inclusion criteria were excluded from the trial before assignment to groups.
Participants by arm
| Arm | Count |
|---|---|
| Recombinant Human Growth Hormone recombinant human growth hormone starting at 2 micrograms/kilograms/day subcutaneously and increased to maximum dose of 6 micrograms/kilograms/day subcutaneously | 27 |
| Placebo placebo subcutaneously once a day | 29 |
| Total | 56 |
Baseline characteristics
| Characteristic | Placebo | Recombinant Human Growth Hormone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 27 Participants | 56 Participants |
| Age Continuous | 47.4 years STANDARD_DEVIATION 6.1 | 46.7 years STANDARD_DEVIATION 7.9 | 47.1 years STANDARD_DEVIATION 6.9 |
| Region of Enrollment United States | 29 participants | 27 participants | 56 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 26 Participants | 26 Participants | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 26 | 5 / 29 |
| serious Total, serious adverse events | 4 / 26 | 1 / 29 |
Outcome results
Primary
Change in Visceral Adipose Tissue Area From Baseline to 18 Months
change in visceral adipose tissue area as measured by single-slice abdominal computed tomographic scan
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Visceral Adipose Tissue Area From Baseline to 18 Months | -22 centimeters squared | Standard Error 6 |
| Placebo | Change in Visceral Adipose Tissue Area From Baseline to 18 Months | -4 centimeters squared | Standard Error 4 |
p-value: 0.04995% CI: [-38, -0.5]repeated measures mixed effects ANCOVA
Secondary
Change in 2-hour Glucose
Change in 2-hour glucose
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in 2-hour Glucose | 16 mg/dL | Standard Error 5 |
| Placebo | Change in 2-hour Glucose | -4 mg/dL | Standard Error 4 |
Secondary
Change in Adiponectin
Change in adiponectin
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Adiponectin | 1.0 mcg/mL | Standard Error 0.3 |
| Placebo | Change in Adiponectin | 0.5 mcg/mL | Standard Error 0.1 |
Secondary
Change in Body Mass Index
Change in body mass index
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Body Mass Index | 0.2 kilogram/meters squared | Standard Error 0.2 |
| Placebo | Change in Body Mass Index | 0.1 kilogram/meters squared | Standard Error 0.1 |
Secondary
Change in Carotid Intima Media Thickness (IMT)
change in carotid intima media thickness (IMT)
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Carotid Intima Media Thickness (IMT) | 0.003 millimeter | Standard Error 0.008 |
| Placebo | Change in Carotid Intima Media Thickness (IMT) | -0.003 millimeter | Standard Error 0.009 |
Secondary
Change in CD4 Cells
Change in CD4 cells
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in CD4 Cells | -19 cells/microliter | Standard Error 13 |
| Placebo | Change in CD4 Cells | 15 cells/microliter | Standard Error 21 |
Secondary
Change in Diastolic Blood Pressure
Change in diastolic blood pressure
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Diastolic Blood Pressure | -3 mm Hg | Standard Error 1 |
| Placebo | Change in Diastolic Blood Pressure | 4 mm Hg | Standard Error 1 |
Secondary
Change in Extremity Fat
Change in extremity fat
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Extremity Fat | 0.3 kilograms | Standard Error 0.1 |
| Placebo | Change in Extremity Fat | 0.3 kilograms | Standard Error 0.1 |
Secondary
Change in Fasting Glucose
change in fasting glucose
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Fasting Glucose | 6 mg/dL | Standard Error 1 |
| Placebo | Change in Fasting Glucose | 5 mg/dL | Standard Error 1 |
Secondary
Change in Insulin-like Growth Factor-I From Baseline to 18 Months
Change in insulin-like growth factor-1
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Insulin-like Growth Factor-I From Baseline to 18 Months | 109 nanograms/milliliter | Standard Error 11 |
| Placebo | Change in Insulin-like Growth Factor-I From Baseline to 18 Months | -25 nanograms/milliliter | Standard Error 8 |
Secondary
Change in Lean Body Mass
change in lean body mass
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Lean Body Mass | 0.8 kilograms | Standard Error 0.3 |
| Placebo | Change in Lean Body Mass | -0.5 kilograms | Standard Error 0.3 |
Secondary
Change in Logarithm HIV Viral Load
Change in logarithm base 10 HIV viral load
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Logarithm HIV Viral Load | 0 log base 10 copies of RNA/milliliter | Standard Error 0.1 |
| Placebo | Change in Logarithm HIV Viral Load | 0 log base 10 copies of RNA/milliliter | Standard Error 0.2 |
Secondary
Change in Quality of Life Score From the Medical Outcomes Study-HIV Survey From Baseline to 18 Months
Change in quality of life score was measured by the Medical Outcomes Study-HIV (MOS-HIV)survey. The MOS-HIV asks patients to report on health-related quality of life and physical function from the past 4 days. The scoring range is 0-100, and a higher score indicates better quality of life.
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Quality of Life Score From the Medical Outcomes Study-HIV Survey From Baseline to 18 Months | -4 units on a scale | Standard Error 3 |
| Placebo | Change in Quality of Life Score From the Medical Outcomes Study-HIV Survey From Baseline to 18 Months | -4 units on a scale | Standard Error 3 |
Secondary
Change in Subcutaneous Adipose Tissue
Change in subcutaneous adipose tissue
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Subcutaneous Adipose Tissue | 4 centimeters squared | Standard Error 4 |
| Placebo | Change in Subcutaneous Adipose Tissue | 4 centimeters squared | Standard Error 4 |
Secondary
Change in Systolic Blood Pressure
Change in systolic blood pressure
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Systolic Blood Pressure | -5 mm Hg | Standard Error 2 |
| Placebo | Change in Systolic Blood Pressure | 1 mm Hg | Standard Error 2 |
Secondary
Change in Triglycerides
Change in triglycerides
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recombinant Human Growth Hormone | Change in Triglycerides | -7 mg/dL |
| Placebo | Change in Triglycerides | 0 mg/dL |
Secondary
Change in Trunk Fat
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Trunk Fat | -0.5 kilograms | Standard Error 0.2 |
| Placebo | Change in Trunk Fat | 0.2 kilograms | Standard Error 0.2 |
Secondary
Change in Trunk to Extremity Ratio
change in trunk to extremity ratio
Time frame: 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Recombinant Human Growth Hormone | Change in Trunk to Extremity Ratio | -0.4 kilogram per kilogram | Standard Error 0.1 |
| Placebo | Change in Trunk to Extremity Ratio | 0 kilogram per kilogram | Standard Error 0 |