Short-term Effects of Leptin in People With Lipodystrophy
Condition: Lipodystrophy
MeSH terms: Lipodystrophy
Intervention: Metreleptin
Intervention description: Recombinant analog of the human hormone, leptin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 14 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Lipodystrophy; Leptin; Energy Expenditure; Diabetes; Hypertriglyceridemia

Summary:

      Background:

      - Lipodystrophy is a condition where people do not have enough fat in the body. People with
      lipodystrophy can have problems such as diabetes or an enlarged liver. Researchers are
      looking at how leptin, a hormone produced by fat cells, can help people with these problems.
      Leptin helps control appetite and how the body stores food. Taking leptin can help people
      with lipodystrophy eat less food, which may help treat diabetes and other problems. To better
      understand how leptin works, researchers want to do an inpatient study on leptin treatment in
      people with lipodystrophy.

      Objectives:

      - To study how leptin treatment affects lipodystrophy.

      Eligibility:

      - Individuals between 14 and 70 years of age who have lipodystrophy.

      Design:

        -  All participants will have a 19-day stay at the National Institutes of Health Clinical
           Center. One group of participants will have tests for 5 days before starting to take
           leptin. They will then take leptin for 2 weeks, and have more tests. The other group of
           participants will have tests for 5 days while taking leptin. They will then take stop
           taking leptin for 2 weeks, and have more tests, and then they will start taking leptin
           again.

        -  Participants will have regular blood and urine tests during the visit. Some of the blood
           tests will look at insulin levels. Some will look at how the body metabolizes sugar and
           fat. Other tests will check hormone levels, especially of reproductive hormones.

        -  During the visit, participants will spend 3 separate days in a metabolic chamber, a
           special room that measures how many calories the body uses. Urine samples will be
           collected during these stays.

        -  Participants will also have several body imaging studies, including magnetic resonance
           imaging and a body composition scan.

        -  Physical activity will be tested with an exercise bicycle and an electronic activity
           monitor.

        -  Participants will be asked questions about hunger and comfort levels throughout the
           stay.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Age 14-70 years (children under age 18 will only be enrolled in the leptin-naive arm
             of the study

          -  Clinically-significant lipodystrophy as defined in protocol 02-DK-0022 (Long Term
             Efficacy of Leptin Replacement in the Treatment of Lipodystrophy). Relevant inclusion
             criteria for enrollment in protocol 02-DK-0022 are (summarized):

               -  Lipodystrophy identified by the study physician during physical examination as an
                  absence of fat outside the range of normal

               -  Circulating leptin levels < 12.0 ng/mL in females and < 8.0 ng/mL in males

               -  Presence of at least one of the following metabolic abnormalities:

                    1. Diabetes as defined by the 2007 American Diabetes Association criteria

                    2. Fasting insulin >30 microU/mL

                    3. Fasting hypertriglyceridemia >200 mg/dL

          -  Co-enrolled in protocol 02-DK-0022 and either:

               -  Leptin naive, with plans to initiate leptin treatment during the current study.
                  For the purpose of this study, leptin naive will be defined as having received no
                  exogenous leptin in the 4 months prior to study participation. Thus, subjects who
                  previously received leptin therapy, discontinued, and wish to restart are
                  eligible.

        Or

        --Leptin treated, meaning the subject has taken a stable dose of exogenous leptin for a
        minimum of 4 months (adults over age 18, only)

        EXCLUSION CRITERIA:

        In leptin treated subjects only, the following exclusion criteria apply:

          -  Poorly controlled diabetes at study entry (hemoglobin A1c greater than or equal to 9%)

          -  Poorly controlled hypertriglyceridemia at study entry (serum triglycerides > 800
             mg/dL)

          -  Extreme hypertriglyceridemia prior to leptin (triglycerides greater than 2000 mg/dL at
             initiation of leptin treatment)

          -  History of chronic or recurrent acute pancreatitis (> 1 episode), or a single episode
             of pancreatitis while receiving leptin treatment

          -  Lipase greater than the upper limit of normal (491 units/L) at study entry

        In all subjects (leptin treated and leptin naive), the following exclusion criteria apply:

          -  Known HIV infection or HIV-associated lipodystrophy

          -  History of diabetic ketoacidosis

          -  Active inflammatory disease (e.g. dermatomyositis)

          -  Change in diabetes or lipid-lowering medications within the past 6 weeks

          -  Estimated glomerular filtration rate < 30 mL/minute

          -  Current or recent (past 2 weeks) use of systemic glucocorticoids

          -  Inadequately controlled hypothyroidism (TSH < 0.4 or >4 mcIU/L) or change in thyroid
             medication in the past 8 weeks.

          -  Pregnancy or breast-feeding

          -  Psychiatric disorder impeding competence or compliance

          -  Any medical condition or medication that will increase risk to the subject (e.g.
             ischemic heart disease, decompensated liver disease) or that will interfere with
             interpretation of study data (e.g. Cushing s syndrome).