Trial record 6 of 21 for:    " December 28, 2011":" January 27, 2012"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

Leptin for Abnormal Lipid Kinetics in HIV Lipodystrophy Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ashok Balasubramanyam, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01511016
First received: January 11, 2012
Last updated: February 4, 2013
Last verified: February 2013
  Purpose

"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.


Condition Intervention
HIV Lipodystrophy
Drug: Human recombinant leptin ("metreleptin")
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Leptin Therapy on Abnormal Lipid Kinetics in Subjects With HIV Lipodystrophy Syndrome

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Rates of lipolysis [ Time Frame: Change from Baseline at 2 and 4 months ] [ Designated as safety issue: No ]
    Rates of total and net lipolysis will be measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate


Secondary Outcome Measures:
  • Rates of fatty acid oxidation [ Time Frame: Change from Baseline at 2 and 4 months. ] [ Designated as safety issue: No ]
    Rates of fatty acid oxidation will be measured in breath samples following stable isotope infusions of 13C-labeled palmitate.

  • Fasting plasma lipids [ Time Frame: Change from Baseline at 2 and 4 months. ] [ Designated as safety issue: No ]
    Fasting plasma cholesterol, HDL-cholesterol and triglycerides will be measured.

  • Glucose levels after glucose challenge [ Time Frame: Change from Baseline at 2 and 4 months. ] [ Designated as safety issue: No ]
    An oral glucose tolerance test will be performed, with measurements of glucose at each time point.

  • Insulin levels after oral glucose challenge. [ Time Frame: Change from Baseline at 2 and 4 months. ] [ Designated as safety issue: No ]
    An oral glucose tolerance test will be performed, with measurements of insulin at each time point


Enrollment: 17
Study Start Date: February 2003
Study Completion Date: October 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: human recombinant leptin (metreleptin)
Each subject will receive 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")
Metreleptin will be 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.
Placebo Comparator: Placebo injection
Each subject will receive 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
Placebo will 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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • predominantly lipoatrophic or mixed phenotype of HIV-lipodystrophy (based on self-observation and evaluation by a study physician utilizing a visual scale;
  • AM fasting leptin < 4.0 ng/ml
  • hypertriglyceridemia (fasting serum TG 250-1000 mg /dl).
  • normal biochemistry (except altered lipid and glucose profile). Patients with the American Diabetes Association diagnostic criteria for diabetes will be included provided the HbA1c level is <7.5% and they have received no anti-diabetic medications for at least 3 months.
  • well-controlled HIV infection status evidenced by viral RNA titers <400 copies/ml, on stable HAART.

Exclusion Criteria:

  • acute or chronic illnesses.
  • use of antidiabetic medications in the previous 3 months, or of lipid-lowering drugs in the previous 6 weeks are also exclusion criteria. Other drugs excluded are growth hormone (if used without evidence of growth hormone deficiency), Megace and testosterone (if used without evidence of hypogonadism).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01511016

Locations
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Ashok Balasubramanyam, MD Baylor College of Medicine
  More Information

Publications:
Responsible Party: Ashok Balasubramanyam, Professor of Medicine, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01511016     History of Changes
Other Study ID Numbers: H-13372
Study First Received: January 11, 2012
Last Updated: February 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
lipid kinetics
fat oxidation

Additional relevant MeSH terms:
HIV-Associated Lipodystrophy Syndrome
HIV Infections
Lipodystrophy
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on September 14, 2014