Blocking growth hormone to help with severe insulin resistance

Phase II Study of Growth Hormone Inhibition Using Pegvisomant In Severe Insulin Resistance

This study is testing if a medication that blocks growth hormone can help people with severe insulin resistance feel better and improve their metabolism.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT05470504 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of pegvisomant, a growth hormone receptor blocker, on individuals with severe insulin resistance due to insulin receptor mutations or partial lipodystrophy. Participants will undergo two hospital stays, where they will receive comprehensive testing, including physical exams, blood tests, and scans to assess their body composition and metabolism. The primary goal is to determine if blocking growth hormone can reduce lipolysis in these patients, potentially improving their insulin sensitivity and metabolic health.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with a known pathogenic variant in the insulin receptor gene or a clinical diagnosis of partial lipodystrophy.

Not a fit: Patients using medications that affect lipolysis or those with certain health conditions, such as anticoagulant use, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve metabolic health and insulin sensitivity in patients with severe insulin resistance.

How similar studies have performed: While this approach is novel in this specific patient population, similar studies targeting growth hormone inhibition have shown promise in other contexts.

Eligibility criteria

* INCLUSION CRITERIA:

To be eligible to participate in this study, an individual must meet all the following criteria:

* Either

  * Known pathogenic variant in the insulin receptor gene, either dominant negative or recessive, OR
  * Clinical diagnosis of partial lipodystrophy based on reduction in adipose tissue outside the normal range in selected adipose depots (including, at a minimum, the gluteofemoral depot) with preservation of adipose tissue in other depots.
* Male or female, aged 18-70 years.
* Completed linear growth and puberty.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

* Use of niacin or other drugs that directly affect lipolysis within 8 weeks prior to enrollment.
* Patients taking anticoagulants (blood thinning medications).
* Use of non-steroidal anti-inflammatory medications (e.g., aspirin, ibuprofen) 2 weeks prior to the biopsy date (in patients who choose to undergo biopsy).
* Changes in medications for diabetes or dyslipidemia within 2 weeks prior to enrollment.
* Pregnancy or lactation.
* For females of reproductive potential: inability or unwillingness to use contraception during study participation and for an additional 1 month after the end of pegvisomant administration.
* For males of reproductive potential: inability or unwillingness to use condoms or other methods to ensure effective contraception with partner during the study and for an additional 1 month after the end of pegvisomant administration.
* Known allergic reactions pegvisomant or any of its components.
* Clinically significant liver disease, evidenced by any of the following:

  * ALT or AST \>3 times the upper limit of normal at screening.
  * Current known liver disease other than steatohepatitis (e.g., autoimmune or viral hepatitis).
  * History of cirrhosis
* Triglycerides \>1500 mg/dL (non-fasting) or \>1000 mg/dL (fasting) at screening.
* In subjects with partial lipodystrophy only, Hemoglobin A1c \>10% at screening.
* Any other medical condition or medication that, in the judgement of the investigator, will increase risk to the subject or impede the measurement of study outcomes.
* Inability of subject to understand or the unwillingness to sign a written informed consent document.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Rebecca J Brown, M.D. — National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Study coordinator: Megan S Startzell, R.N.

Conditions Insulin Receptor Mutation; Partial Lipodystrophy; Pegvisomant; Severe Insulin Resistance; Growth Hormone Inhibition; LIPOLYSIS