HIV Lipodystrophy
Conditions
Keywords
HIV lipodystrophy, growth hormone, growth hormone releasing hormone
Brief summary
The purpose of this study is to examine the short-term effects of two different doses of growth hormone, compared to treatment with growth hormone releasing hormone, on the brain's secretion of growth hormone and the body's glucose metabolism. We hypothesize that growth hormone administration will alter the body's endogenous pulsatile growth hormone secretion and that higher dose growth hormone may decrease insulin sensitivity. We hypothesize that growth hormone releasing hormone will augment endogenous GH pulsatility and be neutral to insulin sensitivity.
Detailed description
The primary objective of this study is to determine the differential effects of growth hormone releasing hormone (GHRH) vs. low dose physiologic growth hormone (GH) vs. higher dose GH treatment and withdrawal on endogenous overnight growth hormone secretion and pulsatility, as well as insulin-stimulated glucose uptake. Subjects with HIV-infection will be randomized to receive one of three treatments: GHRH 2mg/day, or growth hormone 6mcg/kg/day (physiologic low dose), or growth hormone 2mg/day (higher dose) for 2 weeks. At baseline and after two weeks of treatment, we will assess overnight growth hormone by frequent sampling as well as insulin stimulated glucose uptake by clamp. Subjects will then stop the treatment and will return for an identical assessment after a 2 week withdrawal period.
Interventions
DRUGGrowth hormone
Recombinant Human Growth Hormone (Teva pharmaceuticals), with one arm receiving 6mcg/kg SC once daily for two weeks and the other arm receiving 2mg SC once daily for two weeks
DRUGGrowth Hormone Releasing Hormone
Tesamorelin (GHRH) 2mg SC QD x 2 weeks
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
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* previously diagnosed HIV infection * Stable antiretroviral regimen for at least 12 weeks prior to enrollment * Waist circumference \>/= 95cm and waist-to-hip ratio \>/= 0.94 for males or waist circumference \>/=94cm and WHR \>/= 0.88 for females, occurring in the context of treatment for HIV disease * Subjective evidence of at least one of the following changes, occurring during the treatment of HIV disease: increased abdominal girth, relative loss of fat in the extremities, or relative loss of fat in the face
Exclusion criteria
* Use of anti-diabetic agents, Megace, testosterone, or any steroid use within 6 months of the study * Use of GH or Growth hormone releasing factor within six months of starting the study * Change in lipid lowering or antihypertensive regimen within 3 months of screening * Fasting blood sugar \>126mg/dL, SGOT \> 2.5 times ULN, Hgb \< 12.0 g/dL, creatinine \> 1.4 mg/dL, FSH \> 20 IU/L in women, or CD4 count \< 200 * Carpal tunnel syndrome * Severe chronic illness or active malignancy or history of pituitary malignancy or history of colon cancer * For men, history of prostate cancer or evidence of prostate malignancy by PSA \> 5ng/mL * Prior history of hypopituitarism, head irradiation, or any other condition known to affect the GH axis * positive beta-HCG (women only) * Oral contraceptives, depo provera, or combined progesterone-estrogen injections, transdermal contraceptive patches, estrogen or progestin coated IUD's within 6 months of the study * weight \< 110 pounds
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overnight Mean Growth Hormone Secretion After 2 Weeks of Study Drug | after 2 weeks treatment | Serum was sampled for growth hormone concentrations every 20 minutes between 20:00 (8pm) and 07:40 (7:40am). Subjects in GH 6mcg/kg/day and GH 2mg daily groups received their final dose of study drug approximately 36 hours prior to start of sampling. Subjects in Growth Hormone Releasing Hormone group received their final dose of study drug approximately 8 hours prior to start of sampling. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | after two weeks treatment | insulin-stimulated glucose uptake as measured by euglycemic hyperinsulinemic clamp; M value (infusion rate with space correction, using method of DeFronzo) for the steady state between 100-120 minutes of clamp is given |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred between January, 2009 and November, 2012, in the Boston area.
Pre-assignment details
Once patients were found to be eligible (after screen visit) and agreed to participate, there were no additional events prior to baseline.
Participants by arm
| Arm | Count |
|---|---|
| GH 6mcg/kg/d Recombinant human growth hormone 6mcg/kg SC once daily | 8 |
| GH 2mg Daily Recombinant human growth hormone 2mg SC once daily | 12 |
| Growth Hormone Releasing Hormone Growth Hormone Releasing Hormone (Tesamorelin) 2mg daily, injected subcutaneously, x 2 weeks | 5 |
| Total | 25 |
Baseline characteristics
| Characteristic | GH 2mg Daily | Growth Hormone Releasing Hormone | GH 6mcg/kg/d | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 5 Participants | 8 Participants | 25 Participants |
| Age, Continuous | 49 years STANDARD_DEVIATION 6 | 47 years STANDARD_DEVIATION 4 | 49 years STANDARD_DEVIATION 7 | 48 years STANDARD_DEVIATION 6 |
| Region of Enrollment United States | 12 participants | 5 participants | 8 participants | 25 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 8 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 8 | 3 / 11 | 2 / 3 |
| serious Total, serious adverse events | 0 / 8 | 0 / 11 | 0 / 3 |
Outcome results
Primary
Overnight Mean Growth Hormone Secretion After 2 Weeks of Study Drug
Serum was sampled for growth hormone concentrations every 20 minutes between 20:00 (8pm) and 07:40 (7:40am). Subjects in GH 6mcg/kg/day and GH 2mg daily groups received their final dose of study drug approximately 36 hours prior to start of sampling. Subjects in Growth Hormone Releasing Hormone group received their final dose of study drug approximately 8 hours prior to start of sampling.
Time frame: after 2 weeks treatment
Population: Overnight GH data were unavailable for 1 subject in the GH 6mcg/kg group and thus are not included in analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GH 6mcg/kg/d | Overnight Mean Growth Hormone Secretion After 2 Weeks of Study Drug | 0.23 ng/mL |
| GH 2mg Daily | Overnight Mean Growth Hormone Secretion After 2 Weeks of Study Drug | 0.07 ng/mL |
| Growth Hormone Releasing Hormone | Overnight Mean Growth Hormone Secretion After 2 Weeks of Study Drug | 1.24 ng/mL |
Comparison: Kruskal-Wallis Test for overall difference between groupsp-value: 0.01Kruskal-Wallis
Secondary
Insulin Sensitivity
insulin-stimulated glucose uptake as measured by euglycemic hyperinsulinemic clamp; M value (infusion rate with space correction, using method of DeFronzo) for the steady state between 100-120 minutes of clamp is given
Time frame: after two weeks treatment
Population: Insulin stimulated glucose uptake data were unavailable for 4 subjects in the GH 2mg group. Two subjects did not have sufficient IV access and thus could not complete the clamp procedure. Two subjects did not reach target glucose and thus their data could not be used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GH 6mcg/kg/d | Insulin Sensitivity | 9.0 mg/kg/min | Standard Deviation 2.9 |
| GH 2mg Daily | Insulin Sensitivity | 7.5 mg/kg/min | Standard Deviation 3.2 |
| Growth Hormone Releasing Hormone | Insulin Sensitivity | 9.9 mg/kg/min | Standard Deviation 1.2 |
p-value: 0.42ANOVA