Metreleptin for Lipodystrophy

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of metreleptin for people with partial lipodystrophy, a condition that can lead to high blood fat levels and insulin resistance, often resulting in diabetes. Participants will receive metreleptin to determine if it continues to improve their condition. People with partial lipodystrophy who have benefited from metreleptin in previous studies and cannot access it otherwise might be suitable candidates. During the trial, participants will have regular check-ups and tests and will receive metreleptin for home use. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that metreleptin is likely to be safe for humans?

Research shows that metreleptin is generally safe for people with lipodystrophy. A registry collecting data from patients using metreleptin in the U.S. and Europe has provided insights into its safety. This registry indicates that while some side effects can occur, they are usually mild and manageable. Common side effects include minor injection site reactions and headaches.

Additionally, the FDA has approved metreleptin for treating generalized lipodystrophy, confirming it has passed important safety checks. However, individual experiences may vary. Discussing concerns with healthcare providers can help address any questions about starting metreleptin treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lipodystrophy, which often focus on managing symptoms through diet, exercise, and medications that address related complications, metreleptin offers a unique approach by targeting the underlying issue of leptin deficiency. Metreleptin is a recombinant form of the hormone leptin, administered via subcutaneous injections, that directly replaces what's lacking in people with lipodystrophy. Researchers are excited about metreleptin because it addresses the root cause of metabolic problems in lipodystrophy rather than just treating the symptoms, offering the potential for more comprehensive disease management.

What is the effectiveness track record for metreleptin in treating lipodystrophy?

Research has shown that metreleptin, administered as leptin therapy in this trial, can improve health in people with lipodystrophy. It lowers high blood fat levels and aids in controlling insulin resistance. Patients using metreleptin have reported better health outcomes, including improved metabolism. Studies also indicate that metreleptin can enhance quality of life by managing symptoms like high blood sugar. Overall, metreleptin effectively treats metabolic problems related to lipodystrophy. ^{2 6 7 8 9}

Who Is on the Research Team?

Rebecca J Brown, M.D.

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7993583/

Effects of Metreleptin on Patient Outcomes and Quality of Life ... Quality-adjusted life-year gains associated with 12 months of treatment with metreleptin were estimated at 0.313 for generalized and 0.117 for partial ...

2. myalept.com myalept.com/hcp/efficacy

Efficacy | Myalept® (metreleptin) for injection | HCP This phase 3, open-label, single-arm study evaluated Myalept treatment in 48 patients. Patients had to have congenital generalized lipodystrophy (CGL) or ...

3. academic.oup.com academic.oup.com/jcem/article/110/4/e1051/7675889

Effects of Metreleptin in Patients With Generalized ... Metreleptin was shown to be effective in causing sustained improvement in metabolic abnormalities in patients with generalized lipodystrophy (4-6). However, ...

4. ojrd.biomedcentral.com ojrd.biomedcentral.com/articles/10.1186/s13023-023-02714-5

The Metreleptin Effectiveness and Safety Registry (MEASuRE) Metreleptin, a recombinant analog of human leptin, is an approved therapy, adjunct to diet, to treat the metabolic complications of leptin ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02262832

NCT02262832 | Compassionate Use of Metreleptin in ... This study showed that metreleptin ameliorates metabolic and endocrine abnormalities in lipodystrophy, including reducing food intake, improving insulin ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10214317/

The Metreleptin Effectiveness and Safety Registry (MEASuRE) MEASuRE was established to collect data from patients receiving commercially supplied metreleptin in the United States (US) and European Union ( ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02325674

MEASuRE: Metreleptin Effectiveness And Safety Registry This is a non-interventional, multicentre, prospective, observational study of patients receiving treatment with commercial metreleptin for lipodystrophy in ...

8. academic.oup.com academic.oup.com/jes/article/5/4/bvab019/6139135

Effects of Metreleptin on Patient Outcomes and Quality of Life ... Quality-adjusted life-year gains associated with 12 months of treatment with metreleptin were estimated at 0.313 for generalized and 0.117 for ...

9. aetna.com aetna.com/cpb/medical/data/800_899/0882.html?ref=counterforcehealth.org

Metreleptin (Myalept) - Medical Clinical Policy Bulletins Metreleptin is approved by the FDA for treatment of generalized forms of lipodystrophy. In an open-label study, these researchers determined the long-term ...