An interventional study of Human recombinant leptin ("metreleptin") and Placebo in HIV Lipodystrophy, sponsored by Baylor College of Medicine. Completed at 1 site in United States. Open to male participants aged 18 Years to 64 Years. Per ClinicalTrials.gov, last updated 2016-01-27.
Sponsored by Baylor College of Medicine · Not applicable, Interventional, and Treatment
"HIV lipodystrophy syndrome" (HLS) is characterized by loss of fat in the arms and legs, with increase in fat in the abdomen, and abnormal blood lipid levels. Persons with HLS have high risk for cardiovascular disease and diabetes mellitus and the metabolic syndrome. The investigators have previously shown that the abnormal lipid levels and lipodystrophy in HLS are associated with defective regulation of lipid metabolic rates, specifically, accelerated lipolysis (breakdown of stored fats), and decreased fat oxidation (utilization of fats for energy). Patients with HLS also have low levels of the hormone leptin. The investigators hypothesize that treatment of these patients with leptin will improve fat oxidation and may slow the rate of lipolysis. Hence, the investigators propose to study the effect of leptin therapy on lipid metabolic rates and lipid and glucose levels in adults with HLS. The investigators will use state of the art stable isotope tracer techniques and gas chromatography mass spectrometry (GCMS) to measure lipolysis, fat oxidation, and fat re-esterification in adipose tissues and liver.
The HIV lipodystrophy syndrome (HLS) is characterized by peripheral fat wasting and central obesity, and hyperlipidemia (mainly hypertriglyceridemia), which results in insulin resistance. HLS patients are at high risk for cardiovascular disease, diabetes mellitus and the metabolic syndrome.
The investigators have previously shown that the alterations in lipid metabolism in the so-called mixed form of HLS are due to dysregulation of lipid kinetics at two levels. First, there appears to be an acceleration in lipid kinetics, with higher total and net lipolysis despite higher intra-adipocyte re-esterification. However, the percentage of fatty acid flux being oxidized remains the same, leading to increased hepatic recycling of fatty acids to triglycerides (TG), and export of TG-rich VLDL into the circulation. Second, there is reduced clearance of chylomicron and VLDL-TG from the plasma, resulting in the striking hypertriglyceridemia associated with this syndrome. The investigators propose that these alterations in lipid kinetics account for the phenotypic changes characteristic of this syndrome: increased lipolysis would facilitate peripheral lipoatrophy, increased intra-adipocyte re-esterification (if selective in intrabdominal depots) would contribute to the central obesity, and increased hepatic re-esterification together with impaired VLDL- and chylomicron-TG clearance would lead to hypertriglyceridemia.
Rational treatment of HLS should be targeted at these fundamental kinetic defects. Leptin is in many ways an ideal agent, since it increases fat oxidation, and shifts the ratio of utilization of free fatty acids derived from lipolysis towards oxidation and away from re-esterification, and decreases plasma triglyceride levels. HLS patients with lipoatrophy have low circulating levels of leptin. Moreover, leptin has been shown to be effective in correcting similar defects in fat redistribution and circulating lipids in non-HIV forms of lipodystrophy. Hence, the investigators propose to study (using a blinded, placebo-controlled, dose escalating design) the effect of leptin therapy on lipid kinetics and fat distribution in adult subjects with the lipoatrophic and mixed (peripheral lipoatrophy and central adiposity) forms of HLS. The investigators will use state of the art stable isotope tracer techniques and gas chromatography mass spectrometry (GCMS) to measure whole body lipolysis, lipid oxidation, lipid re-esterification and hepatic lipid recycling.
23 studies on the registry are indexed under HIV-Associated Lipodystrophy Syndrome; none are open to participants now.
This study's enrollment of 17 is below the median of 100 across 18 interventional studies indexed under HIV-Associated Lipodystrophy Syndrome.
Browse HIV-Associated Lipodystrophy Syndrome studies →Baylor College of Medicine is the lead sponsor of 734 studies on the registry; 110 are open to participants now.
Of its 83 completed or terminated interventional studies of FDA-regulated products, 44 (53%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Each subject received 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months.
Drug: Human recombinant leptin ("metreleptin")
Each subject received placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months.
Drug: Placebo
Metreleptin was administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months.
Also known as: metreleptin
Placebo was administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months.
Rate of Total Lipolysis
Rate of total lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate
Time frame: 4 months after treatment
Rate of Net Lipolysis
Rate of net lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate
Time frame: 4 months after treatment
Rates of Fatty Acid Oxidation
Rates of fatty acid oxidation were measured in breath samples following stable isotope infusions of 13C-labeled palmitate.
Time frame: 4 months after treatment
Fasting Plasma Non-HDL-C
Fasting plasma non-HDL-cholesterol was calculated from measured total cholesterol and HDL cholesterol.
Time frame: 4 months after treatment.
Glucose Levels After Glucose Challenge
An oral glucose tolerance test was performed. This is not PD/PK in the sense that we are not studying the distribution or clearance of a drug. Rather, we are performing a standard clinical test of glucose tolerance. i.e., a test for diabetes and pre-diabetes. Although multiple time points are used in this test, the outcome is a single value, either a blood glucose level after 2 hours or an area-under-the-curve. In this study we are reporting the area-under-the-curve.
Time frame: 4 months after treatment.
Insulin Levels After Oral Glucose Challenge.
An oral glucose tolerance test was performed to measure endogenous insulin response. This is not PD/PK in the sense that we are not studying the distribution or clearance of a drug. Rather, we are performing a clinical test of endogenous insulin response to glucose i.e., an endocrine test. Although multiple time points are used in this test, the outcome is a single value, i.e., an area-under-the-curve for insulin.
Time frame: 4 months after treatment.
HIV-positive subjects meeting the entry criteria were recruited from March, 2003 until November, 2010 from the clinics of Harris County Hospital District, and Legacy Community Health Center, Houston.
| Milestone | Placebo Injection | Human Recombinant Leptin (Metreleptin) |
|---|---|---|
| Started | 8 | 9 |
| Completed | 6 | 7 |
| Not completed | 2 | 2 |
Rate of total lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate
| mmol FFA/kg/h | Placebo Injection | Human Recombinant Leptin (Metreleptin) |
|---|---|---|
| Rate of Total Lipolysis | 0.649 ± 0.073 | 0.767 ± 0.137 |
Rates of fatty acid oxidation were measured in breath samples following stable isotope infusions of 13C-labeled palmitate.
| mmol FFA/kg/h | Placebo Injection | Human Recombinant Leptin (Metreleptin) |
|---|---|---|
| Rates of Fatty Acid Oxidation | 0.239 ± 0.023 | 0.214 ± 0.040 |
Fasting plasma non-HDL-cholesterol was calculated from measured total cholesterol and HDL cholesterol.
| mg/dL | Placebo Injection | Human Recombinant Leptin (Metreleptin) |
|---|---|---|
| Fasting Plasma Non-HDL-C | 136 ± 9 | 127 ± 7 |
An oral glucose tolerance test was performed. This is not PD/PK in the sense that we are not studying the distribution or clearance of a drug. Rather, we are performing a standard clinical test of glucose tolerance. i.e., a test for diabetes and pre-diabetes. Although multiple time points are used in this test, the outcome is a single value, either a blood glucose level after 2 hours or an area-under-the-curve. In this study we are reporting the area-under-the-curve.
| mg/dL | Placebo Injection | Human Recombinant Leptin (Metreleptin) |
|---|---|---|
| Glucose Levels After Glucose Challenge | 6268 ± 434 | 6647 ± 514 |
An oral glucose tolerance test was performed to measure endogenous insulin response. This is not PD/PK in the sense that we are not studying the distribution or clearance of a drug. Rather, we are performing a clinical test of endogenous insulin response to glucose i.e., an endocrine test. Although multiple time points are used in this test, the outcome is a single value, i.e., an area-under-the-curve for insulin.
| microU/mL | Placebo Injection | Human Recombinant Leptin (Metreleptin) |
|---|---|---|
| Insulin Levels After Oral Glucose Challenge. | 1580 ± 954 | 2868 ± 890 |
Rate of net lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate
| mmol FFA/kg/h | Placebo Injection | Human Recombinant Leptin (Metreleptin) |
|---|---|---|
| Rate of Net Lipolysis | 0.386 ± .074 | 0.508 ± .106 |
Collected over The duration of the study for each subject was 4 months. However, due to slow recruitment the entire study took place over approximately 4 years; therefore the average duration of subject follow-up for Adverse Events was approximately 2 years. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo Injection | — | 1/8 (12.5%) | 0/8 (0%) |
| Human Recombinant Leptin (Metreleptin) | — | 2/9 (22.2%) | 0/9 (0%) |
| Event | Placebo Injection | Human Recombinant Leptin (Metreleptin) |
|---|---|---|
| Weight lossMetabolism and nutrition disorders | 0/8 | 2/9 |
| HyperthyroidismMetabolism and nutrition disorders | 1/8 | 0/9 |
| Age, Categorical(Participants) | Placebo Injection | Human Recombinant Leptin (Metreleptin) | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 8 | 9 | 17 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(years) | Placebo Injection | Human Recombinant Leptin (Metreleptin) | Total |
|---|---|---|---|
| Mean | 49.1 ± 6.8 | 44.9 ± 7.8 | 46.9 ± 7.3 |
| Sex: Female, Male(Participants) | Placebo Injection | Human Recombinant Leptin (Metreleptin) | Total |
|---|---|---|---|
| Female | 0 | 0 | 0 |
| Male | 8 | 9 | 17 |
| Region of Enrollment(participants) | Placebo Injection | Human Recombinant Leptin (Metreleptin) | Total |
|---|---|---|---|
| United States | 8 | 9 | 17 |
This study is completed, as verified in Dec 2015. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
HIV-Associated Lipodystrophy Syndrome→
Baylor College of Medicine