Clinical Trial: Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy

Study Status: Enrolling by invitation
Recruit Status: Enrolling by invitation
Study Type: Interventional

Official Title: Compassionate Use of Metreleptin in Previously-Treated Patients With Generalized Lipodystrophy

Brief Summary:

Background:

- Generalized 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.

Objective:

- To test the safety and effectiveness of metreleptin.

Eligibility:

  • People ages 6 months and older with generalized lipodystrophy who:
  • have received metreleptin through NIH studies AND
  • cannot get it through approved or compassionate use mechanisms in their home country.

Design:

  • 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. 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

    Detailed Summary:

    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 the very rare condition of generalized 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, nonalcoholic 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.

    Currently, metreleptin is not available as an approved drug outside the US and Japan, and it is available on a compassionate use basis only in a few additional countries. The purpose of this study is twofold:

    1. To provide access to metreleptin to patients with generalized lipodystrophy, including those who have previously received metreleptin through NIH studies (protocols 02-DK-0022 and 13-DK- 0057) AND/OR who cannot obtain metreleptin through approved or compassionate use mechanisms in their home country
    2. To continue to collect data on the long-term efficacy of metreleptin in ameliorating the metabolic complications of generalized lipodystrophy. Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

      Current Primary Outcome:

      • Serum triglycerides [ Time Frame: Annually ]
      • Serum hemoglobin A1C [ Time Frame: Annually ]


      Original Primary Outcome: Same as current

      Current Secondary Outcome:

      • Steatohepatosis [ Time Frame: Annually ]
      • Pituitary & Reproductive Function [ Time Frame: Annually ]
      • Ectopic lipid & body composition [ Time Frame: Annually ]
      • Bone mineral density & metabolism [ Time Frame: Annually ]


      Original Secondary Outcome:

      • Steatohepatosis [ Time Frame: Annually ]
      • Pituitary & amp; Reproductive Function [ Time Frame: Annually ]
      • Ectopic lipid & amp; body composition [ Time Frame: Annually ]
      • Bone mineral density & amp; metabolism [ Time Frame: Annually ]


      Information By: National Institutes of Health Clinical Center (CC)

      Dates:
      Date Received: October 10, 2014
      Date Started: October 7, 2014
      Date Completion: July 31, 2018
      Last Updated: May 12, 2017
      Last Verified: January 12, 2017