Insulin Receptor MutationPhase 2NCT05470504
Study of Growth Hormone Inhibition Using Pegvisomant in Severe Insulin Resistance
A Phase 2 study testing Pegvisomant in people with Insulin Receptor Mutation and Partial Lipodystrophy, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Background: Lipodystrophy (LD) syndromes are a group of rare disorders that affect how a person s body can store and use fat tissue. Many people with LDs become severely insulin resistant. Some people are insulin resistant because of a variant in the insulin receptor gene. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Insulin Receptor Mutation, Partial Lipodystrophy
- What is being tested?
- Pegvisomant
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jan 2023to 30 Jan 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: Phase II Study of Growth Hormone Inhibition Using Pegvisomant In Severe Insulin Resistance
Background:
Lipodystrophy (LD) syndromes are a group of rare disorders that affect how a person s body can store and use fat tissue. Many people with LDs become severely insulin resistant. Some people are insulin resistant because of a variant in the insulin receptor gene. Insulin resistance causes many health problems.
Read more
Objective:
To learn if blocking the effects of growth hormone in the body will help people with severe insulin resistance.
Eligibility:
Adults aged 18 to 65 years with either a known variant in the insulin receptor gene or with a diagnosis of partial LD.
Design:
Participants will have 2 hospital stays, about 1 month apart. Each stay will be 3 or 4 nights.
During each hospital stay, participants will have many tests. They will have a physical exam with blood tests. They will have all of their urine collected for a 24-hour period. They will have scans to measure their muscle, bone, and fat tissues. They will have tests to measure metabolism and insulin sensitivity. They may have an optional biopsy of fat tissue.
During the first hospital visit, participants will learn how to give themselves shots of a drug (pegvisomant) that blocks growth hormone. The drug is injected under the skin. Participants will continue to give themselves these shots once a day at home.
After the first hospital visit, participants will talk on the phone with members of the study team once each week. After 2 weeks they will have blood drawn for tests.
Participants will stop the shots after the second hospital visit.
Read the detailed description
STUDY DESCRIPTION
The role of growth hormone (GH) in mediating pathological consequences of inadequate lipid storage will be studied in rare patient populations with high lipolysis and severe metabolic syndrome. Specifically, patients with partial lipodystrophy and pathogenic variants in the insulin receptor gene (INSR) will be studied before and after 1 month of administration of pegvisomant (a GH receptor blocker).
OBJECTIVES
Primary Objective:
Establish proof of concept that GH blockade reduces adipose tissue lipolysis in humans with severe insulin resistance.
Secondary Objectives:
Determine the effects of pegvisomant on lipolytic products and IGF-1.
ENDPOINTS
Primary Endpoint:
Adipose tissue lipolysis measured by glycerol and palmitate rates of appearance using stable isotope tracers.
Secondary Endpoints:
Free fatty acids (FFA), glycerol, IGF-1.
- Conditions
- Insulin Receptor Mutation, Partial Lipodystrophy
- Being tested
- Pegvisomant
- Keywords
- Pegvisomant, Severe Insulin Resistance, Growth Hormone Inhibition, LIPOLYSIS
- Medical subject headings
- Lipodystrophy, Partial, Acquired, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PegvisomantDrug
30 mg subcutaneously every day for 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | open label pegvisomant Receives: Drug: Pegvisomant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glycerol rate of appearance (Ra) normalized to fat mass, Palmitate Ra normalized to fat mass
Estimate the magnitude and variability of the effect of pegvisomant, 30 mg subcutaneously once daily for 1 month, on adipose tissue lipolysis rate in subjects with pathogenic variants in the insulin receptor and partial lipodystrophy.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2022
- Study start23 Jan 2023
- Primary completion30 Jan 2028 (estimated)
- Study completion30 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin Receptor MutationStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Rebecca J Brown, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05470504
- Sponsor's protocol ID
- 10000756
- Other IDs
- 000756-DK
- Status last verified
- 14 Aug 2026
- First submitted
- 16 Jul 2022
- Last updated
- 18 Aug 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Result of the study will be disseminated to participants upon publication.