Metreleptin for Lipodystrophy

Recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 2

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

Must be taking: Metreleptin

Disqualifiers: HIV, Psychiatric disorder, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: Long-term

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

How is the drug Metreleptin unique for treating lipodystrophy?

Metreleptin is unique for treating lipodystrophy because it is a synthetic form of the hormone leptin, which helps regulate fat storage and metabolism, addressing the underlying hormone deficiency in this condition. Unlike other treatments, it directly replaces the missing hormone, potentially improving metabolic abnormalities associated with lipodystrophy. ^{1 2 3 4 5}

Research Team

Rebecca J Brown, M.D.

Principal Investigator

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

Eligibility Criteria

This trial is for people over 6 months old with partial lipodystrophy who've seen health improvements from previous metreleptin treatment in NIH studies but can't access the drug elsewhere. They must have experienced significant benefits like reduced blood fats or better diabetes control and commit to regular local doctor visits.

Inclusion Criteria

I have seen improvements in my health from metreleptin treatment.

I have partial lipodystrophy.

You have been treated with metreleptin in certain previous research studies.

Exclusion Criteria

You are currently abusing alcohol or drugs.

I can get metreleptin through prescription, compassionate use, or a special program.

You have a mental health condition that makes it hard for you to understand or follow the study rules.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metreleptin via SC injections BID, with doses adjusted based on body weight and metabolic control

Long-term

Visits approximately every 6 months during year one, then every 1-2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, with primary outcomes including improvements in serum triglycerides and hemoglobin A1c levels

Ongoing

Regular visits with local doctors and blood tests every 3-6 months at home

Treatment Details

Interventions

• Metreleptin

Trial Overview The trial tests the safety and effectiveness of metreleptin, a medication previously shown to help with insulin resistance and high blood fat levels caused by partial lipodystrophy. Participants will receive metreleptin for daily injections, undergo various health checks, scans, and possibly liver biopsies.

Participant Groups

Group I: Leptin therapy Experimental Treatment 1 Intervention

leptin administered via SC injections BID

Metreleptin is already approved in United States, Canada for the following indications:

Approved in United States as Myalept for:

• Complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy

Approved in Canada as Myalept for:

• Complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy
• Patients with partial lipodystrophy

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Findings from Research

The synthetic peptide ovine beta-lipotropin-(41--91) was produced with a 5% yield and demonstrated significantly enhanced lipolytic activity, being 5.4 times more effective than natural ovine beta-lipotropin.

In terms of melanotropic activity, the synthetic peptide was 2.4 times more active than ovine beta-lipotropin but only 5% as active as bovine beta-melanotropin, indicating its potential for specific therapeutic applications without significant opiate effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and biological activity of ovine beta-lipotropin-(41--91)-henkaipentekontapeptide. Lemaire, S., Yamashiro, D., Li, CH.[2019]

The study developed a new myostatin inhibitor, MID-35, which is a more stable d-peptide compared to the previously studied MIPE-1686, showing equivalent in vitro effectiveness in inhibiting myostatin.

In vivo tests in mice demonstrated that MID-35 significantly increased muscle mass in the tibialis anterior compared to MIPE-1686, suggesting it could be a promising treatment for muscular atrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Myostatin Inhibitory d-Peptides to Enhance the Potency, Increasing Skeletal Muscle Mass in Mice. Takayama, K., Hitachi, K., Okamoto, H., et al.[2023]

A peptide made up of 50 amino acids from ovine beta-lipotropin was successfully synthesized using solid-phase methods, indicating a reliable technique for peptide production.

This synthetic peptide demonstrated lipolytic activity in isolated rabbit fat cells that was approximately six times greater than that of natural beta-lipotropin, suggesting its potential as a more effective agent for fat breakdown.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of a pentekontapeptide with high lipolytic activity corresponding to the carboxyl-terminal fifty amino acids of ovine beta-lipotropin. Yamashiro, D., Li, CH.[2019]

The amino acid sequence of beta-lipotropin from the ostrich pituitary has been identified as consisting of 79 amino acids, providing valuable information for understanding its structure and function.

Comparative analysis shows significant variability in the NH2-terminal regions of beta-lipotropin, beta-melanotropin, and beta-endorphin, suggesting potential differences in their biological roles across species.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

beta-Lipotropin: primary structure of the hormone from the ostrich pituitary gland. Naudé, RJ., Chung, D., Li, CH., et al.[2019]

A new peptide isolated from human pituitary glands exhibits both lipolytic (fat-reducing) and melanotropic (skin pigment-increasing) properties, with a unique amino acid composition that sets it apart from known hormones.

This peptide shows significant activity in stimulating melanocyte function and is effective in promoting lipolysis in rabbit fat cells, although it has limited effectiveness in human cells and is inactive in rat cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of a new lipolytic-melanotropic peptide from human pituitary glands. Smith, G., Gilardeau, C., Lis, M., et al.[2016]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

Synthesis and biological activity of ovine beta-lipotropin-(41--91)-henkaipentekontapeptide. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Development of Myostatin Inhibitory d-Peptides to Enhance the Potency, Increasing Skeletal Muscle Mass in Mice. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Synthesis of a pentekontapeptide with high lipolytic activity corresponding to the carboxyl-terminal fifty amino acids of ovine beta-lipotropin. [2019]

4. Denmark pubmed.ncbi.nlm.nih.gov

beta-Lipotropin: primary structure of the hormone from the ostrich pituitary gland. [2019]

5. Canada pubmed.ncbi.nlm.nih.gov

Isolation of a new lipolytic-melanotropic peptide from human pituitary glands. [2016]