Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy

February 23, 2024 updated by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

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

Background:

- 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.

Objective:

- To test the safety and effectiveness of metreleptin.

Eligibility:

  • 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.

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, 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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

  • INCLUSION 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

EXCLUSION CRITERIA

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Leptin therapy
leptin administered via SC injections BID
Drug: Metreleptin
A leptin analog indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with partial lipodystrophy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum hemoglobin A1C
Time Frame: every 6-12 months
improvement in lab value
every 6-12 months
Serum triglycerides
Time Frame: every 6-12 months
improvement in lab value
every 6-12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 14, 2014

Primary Completion (Estimated)

July 31, 2025

Study Completion (Estimated)

July 31, 2025

Study Registration Dates

First Submitted

October 9, 2014

First Submitted That Met QC Criteria

October 9, 2014

First Posted (Estimated)

October 13, 2014

Study Record Updates

Last Update Posted (Estimated)

February 26, 2024

Last Update Submitted That Met QC Criteria

February 23, 2024

Last Verified

February 22, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 150002
  • 15-DK-0002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

.Subject level data will be shared upon request after appropriate collaboration agreements are in place.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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