Leptin to Treat Lipodystrophy

Learn more about:
Related Clinical Trial
Changes in Weight, Body Composition and Cardiac Risk After Discontinuing Abacavir Treatment in HIV-infected Individuals Changes in Weight, Body Composition and Metabolic Parameters After Discontinuing Dolutegravir or Tenofovir Disproxil Effect of Berberine on Metabolic Syndrome, Efficacy and Safety in Combination With Antiretroviral Therapy in PLWH. Hemoglobin Level, Coagulopathy Profile and Electrolyte Balance Seronegatives and Metabolic Abnormalities Protocol 2 (SAMA002): Study to Compare the Effect of Kaletra and Combivir® in HIV-Negative Healthy Subjects Myocardial Function & FFA Metabolism in HIV Metabolic Syndrome Exercise and Pioglitazone for HIV-Metabolic Syndromes Observational Study of Changes in Fat Distribution and Blood Metabolites in HIV Infected Adults Yoga for the Management of HIV-Metabolic Syndromes Pravastatin for Hyperlipidaemia in HIV. A Study of Physical and Metabolic Abnormalities in HIV Infected and Uninfected Children and Youth Exercise for Patients With HIV Infections Lactate Metabolism Study in HIV Infected Persons Quality of Life, Sleep, and Biomarkers in People With HIV/AIDS The Effect of Efavirenz and Nelfinavir on the Blood Levels of Certain Lipid-Lowering Drugs Metformin and Rosiglitazone, Alone or in Combination, in HIV-Infected Patients With Insulin and Fat Abnormalities Effects of Treatment Changes on Fat Wasting in the Arms and Legs of HIV Patients Safety Study of Antria Cell Preparation Process to Enhance Facial Fat Grafting With Adipose Derived Stem Cells Growth Hormone Dynamics and Cardiac Steatosis in HIV The Effect of Anti-HIV Treatment on Body Characteristics of HIV-Infected Children Immune Response to Pneumococcal Vaccination in Aging HIV Positive Adults Switching From Zidovudine to an NNRTI or Lopinavir/Ritonavir in Patients Treated With Zidovudine/ Lamivudine/Abacavir. Phase 1 Study to Assess the Safety and Tolerability of TAT4 Gel in Healthy Volunteers Detraining in People Living With HIV/AIDS SHARE: Simple HAART With Abacavir, Reyataz, and Epivir The Effects of Anabolic Steroids and Protease Inhibitors on People Living With HIV/AIDS Observational Study of Fat Loss in HIV Infected Adults Taking Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Metabolism and Body Shape of Healthy Children and Children With Chronic Infections Changing to Nonprotease Inhibitor Treatment to Improve Side Effects Safety and Effectiveness of Fenofibrate and Pravastatin in HIV-Positive Patients With Abnormal Blood Lipids Perceived Changes in Body Build and Image in Patients Who Are Now Taking or Recently Have Stopped Taking Anti-HIV Drugs White Light Scanning to Aid Body Contouring: A Pilot Project Treatment of Abnormal Adipose Tissue Accumulation in Human Immunodeficiency Virus (HIV) Patients The Effect of Low-Dose Human Growth Hormone Therapy in HIV Infected Patients Study Comparing Reducing the Dose of Stavudine Versus Switching to Tenofovir in HIV-Infected Patients Receiving Antiretroviral Therapy The Cleveland Cardiometabolic Cohort Metabolic Abnormalities in HIV-infected Persons Clinical Evaluation of Venus Versa Octipolar Applicator for Reduction of Abdomen Circumference Factors Mediating Gut Microbiota Dysbiosis and Metabolic Disease in HIV Patients. Underlying Abnormalities in Fat and Muscle Leading to Lipodystrophy Syndrome Effects of Short-term Growth Hormone in HIV-infected Patients Safety Study of Filler Agent Composed of Autologous Mesenchymal Stem Cells and Hyaluronic Acid Raltegravir Therapy for Women With HIV and Fat Accumulation The PREFORM Study: A Study to Evaluate the Safety and Efficacy of Rotational Fractional Resection on Submental Contouring Effects of IGF-I in HIV Metabolic Disease Combination of Insulin Sensitizer and Leptin as Treatment for the HAART -Induced Metabolic Syndrome Effectiveness of Nucleoside Supplementation or Switch to Tenofovir in Reversing Fat Loss in HIV Infected Adults Lopinavir/r Monotherapy Versus Abacavir/Lamivudine and Lopinavir/r for Limb Fat Recovery in Persons With Lipoatrophy Effects of Growth Hormone Releasing Hormone in HIV A Study of Increased Lactic Acid and Abnormal Fat Distribution in HIV-Positive Patients Effects of a Uridine Supplement on HIV Infected Adults With Lipoatrophy Body Composition and Adipose Tissue in HIV Study to Evaluate Changes in Limb Fat When Switching From a Thymidine Analogue CONFORM: Rotational Fractional Resection for Submental Contouring Study of Alpha-2 Adrenergic Receptor Dysfunction in Regional Lipoatrophy TH9507 in Patients With HIV-Associated Lipodystrophy TH9507 Extension Study in Patients With HIV- Associated Lipodystrophy Study Evaluating the Impact on Fat Distribution of Nucleoside Reverse Transcriptase Inhibitor (NRTI)-Sparing Regimens in Antiretroviral Experienced Patients With Lipoatrophy Energy Expenditure of People Living With HIV/AIDS Beneficial Effect of Insulin Glulisine by Lipoatrophy and Type 1 Diabetes (LAS) Egrifta Replacement and Sleep Disordered Breathing Clinical Trial to Determine the Efficacy of Sculptra™ Dermal Filler for the Correction of Contour Deformities Caused by Lipoatrophy Clinical Trial to Assess the Effect of the Change of Efavirenz (EFV) for Lopinavir/Ritonavir (LPV/r) in Lipoatrophy in HIV-infected Patients Low Energy Diet and Familial Partial Lipodystrophy Clinical Protocol to Investigate the Efficacy of Recombinant Human Leptin (Metreleptin) in Nonalcoholic Steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) Associated With Lipodystrophy A Study to Determine How and Why HIV-Infected Subjects on Anti-viral Treatment Develop Lipodystrophy Adipocyte, Insulin-resistance and Immunity : Evaluation of Interleukin-7 in Lipodystrophy, Diabetes and Obesity Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy Role of the Autonomic Nervous System in HIV-Lipodystrophy Leptin for Abnormal Lipid Kinetics in HIV Lipodystrophy Syndrome Therapeutic Approaches to HAART-Induced Lipodystrophy Different Surgical Modalities for Thigh Lipodystrophy Including Liposuction,Thigh Lift and Liposuction Assisted Thigh Lift Leptin to Treat Lipodystrophy Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy Prevalence of Lipodystrophy Syndrome and Its Role as Cause of Metabolic Disturbances Efficacy, Safety and Tolerability of ISIS 304801 in People With Partial Lipodystrophy With an Open-Label Extension Shock Waves for Treatment of Gynoid Lipodystrophy and Localized Fat Corticosteroid-induced Lipodystrophy and Adipokines Short-term Effects of Leptin in People With Lipodystrophy Leptin to Treat Lipodystrophy Lipodystrophy Connect Patient Registry An Open-Label Treatment Protocol to Provide Metreleptin for the Treatment of Diabetes Mellitus and/or Hypertriglyceridemia Associated With Lipodystrophy Autologous Adipose-Derived Stem Cell Transplantation in Patients With Lipodystrophy

Brief Title

Leptin to Treat Lipodystrophy

Official Title

Efficacy of Leptin Replacement in Treatment of Lipodystrophy

Brief Summary

      This study will evaluate the safety and effectiveness of the leptin replacement therapy in
      treating lipoatrophy or lipodystrophy-a condition in which there is a total or partial loss
      of fat cells. Patients with lipodystrophy lack sufficient leptin, because this hormone is
      produced by fat cells. The leptin deficiency usually causes high blood lipid (fat) levels and
      insulin resistance that may lead to diabetes. Patients may have hormone imbalances, fertility
      problems, uncontrolled appetite, and liver disease due to fat accumulation.

      Patients 15 years and older with lipodystrophy are eligible for this study. Candidates are
      screened with a medical history and physical examination, and fasting blood tests. Those
      enrolled undergo the following additional procedures:

        -  Ultrasound of the liver and, if abnormalities are found, possibly a liver biopsy

        -  Resting metabolic rate measurement - measures the amount of oxygen breathed at rest in
           order to calculate how many calories are required to maintain resting body functions

        -  Magnetic resonance imaging of the liver and other organs, and of muscle and fat

        -  Estimation of body fat - measurements of height, weight, hip size, and skin folds over
           the arms and abdomen to estimate body fat content

        -  Insulin tolerance test - measures blood glucose levels after administration of insulin.
           Insulin is given through an intravenous (IV) catheter (a thin tube placed in a vein) and
           blood is drawn 5 minutes before the test begins, when the test begins, and 5, 10, 15, 20
           and 30 minutes into the test

        -  Oral glucose tolerance test - measures blood glucose and insulin levels after drinking a
           glucose (sugar) solution. Blood samples are drawn through an IV catheter 15 minutes
           before the test begins, at the time the test begins, and 30, 60, 90 and 180 minutes into
           the test

        -  Intravenous glucose tolerance test - measures tissue response to insulin and glucose
           after glucose is injected into a vein. The glucose injection is followed by a short
           infusion of insulin and then blood samples are taken over 3 hours to measure insulin and
           glucose levels

        -  Appetite level and food intake - measures hunger level and caloric intake. Patients are
           questioned about their hunger level, given a variety of foods they may choose to eat and
           questioned again at various intervals about hunger level. On another day, patients are
           given breakfast (usually a milkshake) and when they want to eat again, the appetite
           level and caloric intake study is repeated.

        -  Hormone function tests - the function of three hormones influenced by leptin
           (corticotropin-releasing hormone, thyrotropin-releasing hormone and luteinizing
           hormone-releasing hormone) are assessed. The hormones are injected intravenously and
           then blood samples are drawn.

      When all the tests are completed, leptin therapy begins. The drug is injected under the skin
      twice a day for 4 months by the patient or a caregiver (similar to self-administered insulin
      injections for diabetes). Blood is drawn once a month to monitor the effects of treatment and
      drug side effects. At clinic visits scheduled 1, 2 and 4 months after therapy starts,
      patients have a physical examination and meet with a dietitian. Medication dosage is also
      increased at these visits. At the end of 4 months, all baseline studies described above are
      repeated. Throughout the study, all patients complete a form once a week, in which they
      record their symptoms. Patients with diabetes also measure their blood glucose levels at home
      before each meal and at bedtime.
    

Detailed Description

      Lipoatrophic diabetes is a syndrome characterized by insulin resistance in association with a
      paucity of adipose tissue. Patients with severe lipoatrophy die prematurely, typically from
      the complications of diabetes or liver disease. Experiments with lipoatrophic mice suggest
      that the insulin resistance is caused by the lack of adipose tissue. Adipose tissue normally
      produces leptin, a hormone that increases insulin action. To what extent does leptin
      deficiency cause diabetes in lipoatrophic patients? In one mouse model of lipoatrophy, leptin
      administration reversed the diabetes and liver disease. In a different, more severely
      adipose-deficient mouse, the effects of leptin treatment were detectable, but more modest.

      In this protocol, to be carried out at both the NIH and the University of Texas in Dallas, we
      test the hypotheses that leptin can be safely administered to patients with lipoatrophic
      diabetes and they will benefit from treatment with A-100 (recombinant form of human leptin
      provided by Amgen). We will study patients with lipoatrophy, low leptin levels, and at least
      one of the following metabolic abnormalities: severe insulin resistance, diabetes, and/or
      hypertriglyceridemia.

      We will treat patients with A-100 injections for four months, with inpatient studies at
      baseline, 1, 2, and 4 months of treatment. In the core protocol, we will monitor metabolic
      control (e.g. glucose, insulin, free fatty acid, and triglyceride levels). Ancillary studies
      will evaluate the effect of A-100 on the gonadal axis and on liver pathology.

      After 8 months of treatment, we will offer a withdrawal study to the patient requiring an
      inpatient admission and controlled diet. Afterwards leptin therapy will resume in a long-term
      extension study with follow up visits every 6 months. Metabolic parameters will continue to
      be followed, along with body fat imaging studies, gonadotropin monitoring, and liver function
      analysis.
    

Study Phase

Phase 2

Study Type

Interventional




Condition

Lipodystrophy

Intervention

hu Leptin (A-100)


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

20

Start Date

June 2000

Completion Date

April 2003


Eligibility Criteria

        INCLUSION CRITERIA:

        All ethnic groups

        Males and females

        Age greater than 14 years

        Clinically-significant lipodystrophy, identified by the study physician during the physical
        examination as an absence of fat outside the range of normal variation and/or identified as
        a disfiguring factor by the patient.

        Circulating leptin levels less than 4.0 ng/ml in females and less than 3.0 ng/ml in males
        as measured by Linco assay on at least 2 occasions.

        Presence of at least one of the following metabolic abnormalities:

        Presence of diabetes as defined by the 1997 ADA criteria: a) fasting plasma glucose greater
        than or equal to 126 mg/dL, or b) 2 hour plasma glucose greater than or equal to 200 mg/dL
        following a 75 gram oral glucose load, or c) diabetic symptoms with a random plasma glucose
        greater than or equal to 200 mg/dL.

        Fasting insulin greater than 30 micrograms/ml;

        Fasting hypertriglyceridemia greater than 200 mg/dl.

        EXCLUSION

        General: Pregnant women, women in their reproductive years who do not use an effective
        method of birth control, women currently nursing or lactating within 6 weeks of having
        completed nursing, and persons who are unable to provide informed consent will be excluded
        from the study.

        Exclusions for underlying disease likely to increase side effects or to hinder objective
        data collection:

        Known liver disease due to causes other than non-alcoholic steatohepatitis

        Current alcohol or substance abuse

        Psychiatric disorder impeding competence or compliance

        Active tuberculosis

        Use of anorexiogenic drugs

        Other condition which in the opinion of the clinical investigators would impede completion
        of the study

        Subjects who have a known hypersensitivity to E. Coli derived proteins
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00005905

Organization ID

000146

Secondary IDs

00-DK-0146


Study Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)


Study Sponsor

, , 


Verification Date

April 2003