Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy

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Brief Title

Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy

Official Title

Compassionate Use of Metreleptin in Previously-Treated Patients With Partial Lipodystrophy

Brief Summary


      - Partial lipodystrophy can cause high blood fat levels and resistance to insulin. This can
      lead to health problems including diabetes. Researchers have found that the drug metreleptin
      improves health in people with this disease.


      - To test the safety and effectiveness of metreleptin.


        -  People age 6 months and older with partial lipodystrophy who

        -  have received metreleptin through NIH studies and shown improvement AND

        -  cannot get metreleptin other ways.


        -  Participants will come to NIH approximately every 6 months during year one, then every 1
           2 years. Financial assistance may be available for travel within the U.S.

        -  At visits, participants will get a supply of metreleptin to take home for daily
           injections, or it can be shipped to them inside the U.S. They will have:

        -  plastic catheter placed in an arm vein.

        -  blood tests, urine collection, and physical exam.

        -  oral glucose tolerance test, drinking a sweet liquid.

        -  ultrasound of the heart, liver, uterus, and ovaries. A gel and a probe are placed on the
           skin and pictures are taken of the organs.

        -  echocardiogram, which takes pictures of the heart with sound waves.

        -  Resting Metabolic Rate taken. A plastic hood is worn over the head while the oxygen they
           breathe is measured.

        -  Participants will have up to 3 DEXA scan x-rays per year.

        -  Participants may have:

        -  annual bone x-rays.

        -  liver biopsies every few years. A needle will be inserted into the liver to obtain a
           small piece. Participants will sign a separate consent for this.

        -  Participants must be seen regularly by their local doctors and have blood tests at least
           every 3-6 months at home.

Detailed Description

      Leptin is an adipocyte-derived hormone that can be thought of as a signal from adipose tissue
      to the rest of the body conveying information about long-term nutritional status. Patients
      with lipodystrophy have leptin deficiency secondary to lack of adipose tissue. The
      combination of leptin deficiency and ectopic lipid deposition in patients with lipodystrophy
      leads to metabolic complications including severe insulin resistance and diabetes,
      hypertriglyceridemia, non-alcoholic steatohepatitis, and polycystic ovarian syndrome. Between
      2000 and 2014, the NIDDK IRP conducted an open-label clinical trial of the recombinant human
      leptin analog, metreleptin, in patients with generalized and partial forms of lipodystrophy.
      This study showed that metreleptin ameliorates metabolic and endocrine abnormalities in
      lipodystrophy, including reducing food intake, improving insulin resistance and diabetes,
      reducing ectopic lipid, and normalizing reproduction. Based on these data, metreleptin was
      approved by the FDA in February, 2014, for patients with generalized, but not partial,
      lipodystrophy. Our data have shown, however, that a subgroup of patients with partial
      lipodystrophy do gain medical benefit from metreleptin.

      The purpose of this study is twofold:

        -  To provide access to metreleptin to patients with partial lipodystrophy who have
           previously received and derived benefit from metreleptin through NIH studies (protocols
           02-DK-0022 and 13-DK-0057).

        -  To continue to collect data on the long-term efficacy of metreleptin in ameliorating the
           metabolic complications of partial lipodystrophy.

      Metreleptin will be given at doses of less than or equal to 0.24 mg/kg/day, adjusted based on
      body weight and metabolic control. Patients will be seen approximately once per year at NIH
      for evaluation, and potentially less frequently for those who are medically stable and have
      difficulty traveling to NIH. Laboratory evaluation will be obtained more frequently by the
      patient s home providers as clinically indicated. The primary outcomes of the study are
      improvements in serum triglycerides and hemoglobin A1c levels. Secondary outcomes include
      measures of steatohepatitis and ectopic lipid, body composition, bone mineral density and
      bone mineral metabolism, and pituitary and reproductive function.

      Metreleptin is supplied by Amryt Pharma, Incorporated. Neither the NIH nor Amryt Pharma can
      guarantee that leptin will be available indefinitely and/or after the study ends.

Study Phase

Phase 2

Study Type


Primary Outcome

Serum hemoglobin A1C





Study Arms / Comparison Groups

 Leptin therapy
Description:  leptin administered via SC injections BID


* 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


Estimated Enrollment


Start Date

October 14, 2014

Completion Date

July 31, 2025

Primary Completion Date

July 31, 2025

Eligibility Criteria


          -  Age greater than or equal to 6 months

          -  Partial lipodystrophy (either genetic or acquired)

          -  Previously or currently treated with metreleptin under NIH study 02-DK-0022 and/or NIH
             study 13-DK-0057.

          -  Documented metabolic benefit from prior or current metreleptin treatment, defined as
             one or more of the following:

               -  TG reduction greater than or equal to 30% OR

               -  HbA1c reduction greater than or equal to 1% OR

               -  Decrease in insulin requirements greater than or equal to 40% OR

               -  Decrease in episodes of pancreatitis OR

               -  Improvement in steatohepatitis OR

               -  Withdrawal of metreleptin led to marked worsening of metabolic parameters


          -  Availability of metreleptin to the patient either as an approved drug, or through
             local compassionate use or expanded access programs.

          -  Known HIV infection or HIV-associated lipodystrophy.

          -  Psychiatric disorder impeding competence or compliance.

          -  Any medical condition or medication that will increase risk to the subject.

          -  Current alcohol or substance abuse.

          -  Subjects who have a known hypersensitivity to E. coli derived proteins.




6 Months - N/A

Accepts Healthy Volunteers



Rebecca J Brown, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

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

Study Sponsor

Rebecca J Brown, M.D., Principal Investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Verification Date

February 22, 2022