HAART-induced Lipodystrophy and Metabolic Syndrome
Conditions
Keywords
leptin, lipodystrophy, insulin resistance, hyperlipidemia, metabolic syndrome
Brief summary
The purpose of this study is to examine whether replacing leptin to normal levels can reverse the changes in fat distribution, lipid profile, and other metabolic problems associated with highly active antiretroviral therapy (HAART)-induced lipodystrophy and metabolic syndrome in HIV patients.
Detailed description
Exposure to HIV medications has been associated with metabolic changes including generalized fat depletion (lipoatrophy), high triglyceride levels, and in some patients, high sugar levels or diabetes. This syndrome is associated with a deficiency of leptin, a hormone produced by fat cells. Recent studies involving leptin administration to patients with congenital lipoatrophy have shown dramatic improvements in metabolic parameters such as insulin resistance and hyperlipidemia. Leptin administration to patients with HAART-induced lipoatrophy may also lead to significant improvements in the metabolic abnormalities found in these HIV+ patients. The aims of this study are to examine the effect of leptin administration on insulin resistance and other parameters of the metabolic syndrome in HIV patients with HAART-induced lipoatrophy. Comparison: Leptin-treated group to placebo-treated group
Interventions
DRUGr-metHuLeptin
DRUGPlacebo
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Amgen
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years old * Documented HIV infection * Exposed to at least 6 months of cumulative highly active antiretroviral medications for HIV * Developed fat depletion after starting HIV medications * Low leptin level in the blood * Fasting triglyceride level \> 300 mg/dl
Exclusion criteria
* Active infectious diseases, except HIV * Diabetes prior to starting HIV medications * Alcohol or drug abuse * Triglyceride level \> 1000 mg/dl * Significant kidney, liver, or thyroid dysfunction * Cancer or lymphoma * Pregnancy or planning to become pregnant during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Serum Lipid Levels | At the end of each two month intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glycemia (as Assessed by Fasting Glucose) | At the end of each two month intervention | — |
| Low Density Lipoprotein (LDL) Cholesterol Levels | At the end of each two month intervention | — |
| Free Fatty Acid (FFA) Levels | At the end of each two month intervention | — |
| Blood Pressure | At the end of each two month intervention | percent change in mean blood pressure |
| Fibrinogen | At the end of each two month intervention | Fibrinogen |
| Insulin Resistance (as Assessed by HOMA-IR) | At the end of each two month intervention | — |
| Lean Body Mass | At the end of each two month intervention | lean body mass |
| Viral Load | At the end of each two month intervention | — |
| CD4+ Lymphocytes | At the end of each two month intervention | — |
| Interleukin-6 (IL-6) Levels | At the end of each two month intervention | — |
| Hepatic Fat Content | At the end of each two month intervention | — |
| Insulin Levels | At the end of each two month intervention | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants r-MetHuLeptin SubQ once daily
r-metHuLeptin/placebo then placebo/r-metHuLeptin | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age, Continuous | 45.8 years STANDARD_DEVIATION 2 |
| Body mass index | 22.2 kg/m^2 STANDARD_DEVIATION 0.83 |
| CD4 count | 454 cells/μl STANDARD_DEVIATION 94 |
| Fasting leptin concentration | 1.34 ng/ml STANDARD_DEVIATION 0.2 |
| glucose | 81.1 mg/dl STANDARD_DEVIATION 6.7 |
| hemoglobin A1c | 5.1 % STANDARD_DEVIATION 0.3 |
| HIV viral load | 24524 copies/ml STANDARD_DEVIATION 13693 |
| insulin | 11.5 micro international units(μIU)/ml STANDARD_DEVIATION 2.7 |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 7 Participants |
| triglycerides | 530 mg/dl STANDARD_DEVIATION 53.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 0 / 7 |
| serious Total, serious adverse events | 0 / 5 | 0 / 7 |
Outcome results
Primary
Serum Lipid Levels
Time frame: At the end of each two month intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| r-MetHuLeptin | Serum Lipid Levels | low density lipoprotein cholesterol | 113.0 mg/dl | Standard Error 12.7 |
| r-MetHuLeptin | Serum Lipid Levels | high density lipoprotein cholesterols | 35 mg/dl | Standard Error 2.23 |
| r-MetHuLeptin | Serum Lipid Levels | triglycerides | 409.0 mg/dl | Standard Error 88.8 |
| r-MetHuLeptin | Serum Lipid Levels | Free fatty acids | 0.45 mg/dl | Standard Error 0.07 |
| r-MetHuLeptin | Serum Lipid Levels | total cholesterol | 228.8 mg/dl | Standard Error 13.3 |
| Placebo | Serum Lipid Levels | Free fatty acids | 0.61 mg/dl | Standard Error 0.09 |
| Placebo | Serum Lipid Levels | total cholesterol | 219.7 mg/dl | Standard Error 13.1 |
| Placebo | Serum Lipid Levels | low density lipoprotein cholesterol | 105.7 mg/dl | Standard Error 3.33 |
| Placebo | Serum Lipid Levels | triglycerides | 520.5 mg/dl | Standard Error 91.1 |
| Placebo | Serum Lipid Levels | high density lipoprotein cholesterols | 29.96 mg/dl | Standard Error 2.25 |
Secondary
Blood Pressure
percent change in mean blood pressure
Time frame: At the end of each two month intervention
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| r-MetHuLeptin | Blood Pressure | 3.2 percentage change of mean blood pressure | Standard Error 5.7 |
| Placebo | Blood Pressure | -6.7 percentage change of mean blood pressure | Standard Error 6.4 |
Secondary
CD4+ Lymphocytes
Time frame: At the end of each two month intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| r-MetHuLeptin | CD4+ Lymphocytes | 556.6 cells/mcl | Standard Error 135 |
| Placebo | CD4+ Lymphocytes | 637.2 cells/mcl | Standard Error 158.4 |
Secondary
Fibrinogen
Fibrinogen
Time frame: At the end of each two month intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| r-MetHuLeptin | Fibrinogen | 252.2 mg/dL | Standard Error 16.3 |
| Placebo | Fibrinogen | 294.4 mg/dL | Standard Error 14.58 |
Secondary
Free Fatty Acid (FFA) Levels
Time frame: At the end of each two month intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| r-MetHuLeptin | Free Fatty Acid (FFA) Levels | 0.45 mEq/liter | Standard Error 0.07 |
| Placebo | Free Fatty Acid (FFA) Levels | 0.61 mEq/liter | Standard Error 0.09 |
Secondary
Glycemia (as Assessed by Fasting Glucose)
Time frame: At the end of each two month intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| r-MetHuLeptin | Glycemia (as Assessed by Fasting Glucose) | 91 mg/dl | Standard Error 2.28 |
| Placebo | Glycemia (as Assessed by Fasting Glucose) | 95.6 mg/dl | Standard Error 2.8 |
Secondary
Hepatic Fat Content
Time frame: At the end of each two month intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| r-MetHuLeptin | Hepatic Fat Content | 4.02 percentage of liver volume | Standard Error 3.15 |
| Placebo | Hepatic Fat Content | 4.01 percentage of liver volume | Standard Error 2.65 |
Secondary
Insulin Levels
Time frame: At the end of each two month intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| r-MetHuLeptin | Insulin Levels | 11.6 mcIU/ml | Standard Error 4.46 |
| Placebo | Insulin Levels | 20.3 mcIU/ml | Standard Error 7.04 |
Secondary
Insulin Resistance (as Assessed by HOMA-IR)
Time frame: At the end of each two month intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| r-MetHuLeptin | Insulin Resistance (as Assessed by HOMA-IR) | 2.52 units on a scale | Standard Error 0.91 |
| Placebo | Insulin Resistance (as Assessed by HOMA-IR) | 4.56 units on a scale | Standard Error 1.43 |
Secondary
Interleukin-6 (IL-6) Levels
Time frame: At the end of each two month intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| r-MetHuLeptin | Interleukin-6 (IL-6) Levels | 1.65 pg/ml | Standard Error 0.38 |
| Placebo | Interleukin-6 (IL-6) Levels | 2.14 pg/ml | Standard Error 0.53 |
Secondary
Lean Body Mass
lean body mass
Time frame: At the end of each two month intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| r-MetHuLeptin | Lean Body Mass | 58.6 kg | Standard Error 4.41 |
| Placebo | Lean Body Mass | 61.6 kg | Standard Error 4.26 |
Secondary
Low Density Lipoprotein (LDL) Cholesterol Levels
Time frame: At the end of each two month intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| r-MetHuLeptin | Low Density Lipoprotein (LDL) Cholesterol Levels | 113 mg/dl | Standard Error 12.7 |
| Placebo | Low Density Lipoprotein (LDL) Cholesterol Levels | 105.7 mg/dl | Standard Error 3.33 |
Secondary
Viral Load
Time frame: At the end of each two month intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| r-MetHuLeptin | Viral Load | 11345 copies/ml | Standard Error 10596 |
| Placebo | Viral Load | 12367 copies/ml | Standard Error 11861 |