Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy
Primary Purpose
Lipodystrophy, Diabetes, Hyperlipidemia
Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Metreleptin
Sponsored by
About this trial
This is an interventional treatment trial for Lipodystrophy focused on measuring Diabetes, Leptin, Lipodystrophy, Hypertriglyceridemia
Eligibility Criteria
INCLUSION CRITERIA:
- Age greater than or equal to 6 months.
- Generalized lipodystrophy (either congenital or acquired).
- Those who cannot obtain metreleptin through approved or compassionate use mechanisms in their home country.
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.
- 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 (as leptin is derived from such proteins).
Sites / Locations
- National Institutes of Health Clinical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Leptin study drug
Arm Description
Administration of study drug SQ BID
Outcomes
Primary Outcome Measures
Serum triglycerides
Improvements in lab value.
Serum hemoglobin A1C
Improvements in lab value.
Secondary Outcome Measures
Steatohepatosis
stable or improvements
Pituitary & Reproductive Function
stable or improvements
Ectopic lipid & body composition
stable or improvements
Bone mineral density & metabolism
stable or improvements
Full Information
NCT ID
NCT02262832
First Posted
October 10, 2014
Last Updated
September 30, 2023
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT02262832
Brief Title
Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy
Official Title
Compassionate Use of Metreleptin in Previously-Treated Patients With Generalized Lipodystrophy
Study Type
Interventional
2. Study Status
Record Verification Date
September 11, 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 9, 2014 (Actual)
Primary Completion Date
July 31, 2025 (Anticipated)
Study Completion Date
July 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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 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 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:
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
To continue to collect data on the long-term efficacy of metreleptin in ameliorating the metabolic complications of generalized 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 the US. 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. Neither the NIH nor Amryt Pharma can guarantee that leptin will be available for these patients indefinitely and/or after the study ends.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lipodystrophy, Diabetes, Hyperlipidemia
Keywords
Diabetes, Leptin, Lipodystrophy, Hypertriglyceridemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Leptin study drug
Arm Type
Other
Arm Description
Administration of study drug SQ BID
Intervention Type
Drug
Intervention Name(s)
Metreleptin
Intervention Description
administered subcutaneously 1-2 times/day
Primary Outcome Measure Information:
Title
Serum triglycerides
Description
Improvements in lab value.
Time Frame
every 6-12 months
Title
Serum hemoglobin A1C
Description
Improvements in lab value.
Time Frame
every 6-12 months
Secondary Outcome Measure Information:
Title
Steatohepatosis
Description
stable or improvements
Time Frame
every 12 months
Title
Pituitary & Reproductive Function
Description
stable or improvements
Time Frame
every 6-12 months
Title
Ectopic lipid & body composition
Description
stable or improvements
Time Frame
every 12 months
Title
Bone mineral density & metabolism
Description
stable or improvements
Time Frame
every 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
98 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA:
Age greater than or equal to 6 months.
Generalized lipodystrophy (either congenital or acquired).
Those who cannot obtain metreleptin through approved or compassionate use mechanisms in their home country.
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.
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 (as leptin is derived from such proteins).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Megan S Startzell, R.N.
Phone
(301) 402-6371
Email
megan.startzell@nih.gov
First Name & Middle Initial & Last Name or Official Title & Degree
Rebecca J Brown, M.D.
Phone
(301) 594-0609
Email
brownrebecca@mail.nih.gov
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rebecca J Brown, M.D.
Organizational Affiliation
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
Phone
800-411-1222
Ext
TTY dial 711
Email
ccopr@nih.gov
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
.Subject level data will be shared upon request after appropriate collaboration agreements are in place.
Citations:
PubMed Identifier
30847226
Citation
Malandrino N, Reynolds JC, Brychta RJ, Chen KY, Auh S, Gharib AM, Startzell M, Cochran EK, Brown RJ. Visceral fat does not contribute to metabolic disease in lipodystrophy. Obes Sci Pract. 2019 Jan 24;5(1):75-82. doi: 10.1002/osp4.319. eCollection 2019 Feb.
Results Reference
background
PubMed Identifier
30237235
Citation
Meral R, Ryan BJ, Malandrino N, Jalal A, Neidert AH, Muniyappa R, Akinci B, Horowitz JF, Brown RJ, Oral EA. "Fat Shadows" From DXA for the Qualitative Assessment of Lipodystrophy: When a Picture Is Worth a Thousand Numbers. Diabetes Care. 2018 Oct;41(10):2255-2258. doi: 10.2337/dc18-0978.
Results Reference
background
PubMed Identifier
28324110
Citation
Brown RJ, Meehan CA, Cochran E, Rother KI, Kleiner DE, Walter M, Gorden P. Effects of Metreleptin in Pediatric Patients With Lipodystrophy. J Clin Endocrinol Metab. 2017 May 1;102(5):1511-1519. doi: 10.1210/jc.2016-3628.
Results Reference
derived
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2015-DK-0003.html
Description
NIH Clinical Center Detailed Web Page
Learn more about this trial
Compassionate Use of Metreleptin in Previously Treated People With Generalized Lipodystrophy
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