Severe Insulin ResistancePhase 2NCT00085982

Effect of Metreleptin Therapy in the Treatment of Severe Insulin Resistance

A Phase 2 study testing Metreleptin in people with Severe Insulin Resistance, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Study Description: Patients with mutations of the insulin receptor have diabetes that is challenging to control with conventional therapies, leading to early morbidity and mortality. We hypothesize that recombinant leptin (metreleptin) in these patients will improve glycemia control. Read more about this study

Who is it for?: Ages 5 years and older
Conditions the study is for: Severe Insulin Resistance
What is being tested?: Metreleptin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 11 participants
Where: 1 siteUnited States
Study dates: 21 Aug 2003to 1 Jan 2030
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 5 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Provision of signed and dated informed consent form
Male or female, aged > 5 years
Clinically significant, severe insulin resistance caused by a known or suspected defect in the insulin receptor
Presence of at least one of the following metabolic abnormalities:
Fasting insulin >30 micro U/ml, or
Presence of diabetes as defined by the 2006 American Diabetes Association (ADA) criteria:

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Fasting plasma glucose >= 126 mg/dL
2 hour plasma glucose >= 200 mg/dL following a 75 gram (1.75g/kg if less than 40kg) oral glucose load, or
Diabetic symptoms with a random plasma glucose >= 200 mg/dL

Who cannot join

Pregnant at time of enrollment, women in their reproductive years who do not use an effective method of birth control, and women currently nursing or lactating within 6 weeks of having completed nursing.
Known infectious liver disease
Known HIV infection
Current alcohol or substance abuse
Active tuberculosis
Use of anorexigenic drugs
Other conditions which in the opinion of the clinical investigators would impede completion of the study.
Subjects who have a known hypersensitivity to E. Coli derived proteins.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Phase II Trial of Effect of Metreleptin Therapy in Severe Insulin Resistance

Study Description:

Patients with mutations of the insulin receptor have diabetes that is challenging to control with conventional therapies, leading to early morbidity and mortality. We hypothesize that recombinant leptin (metreleptin) in these patients will improve glycemia control.

Objectives:

Primary Objective: To determine if 1 year of metreleptin will improve glycemia control in patients with genetic defects of the insulin receptor. Secondary Objectives: To determine mechanisms by which metreleptin improves glycemia.

Endpoints:

Primary Endpoint: Hemoglobin A1c.

Secondary Endpoints: fasting plasma glucose, fasting insulin/C-peptide, glucose/insulin/C-peptide area under the curve during oral glucose tolerance test.

Study Population:

20 male or female patients with mutations of the insulin receptor, age (Bullet)5 years, at the NIH Clinical Center.

Description of Sites/Facilities Enrolling Participants: Description of Study Intervention:

NIH Clinical Center

Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day).

Read the detailed description

Study Description:

Objectives:

Endpoints:

Primary Endpoint: Hemoglobin A1c.

Secondary Endpoints: fasting plasma glucose, fasting insulin/C-peptide, glucose/insulin/C-peptide area under the curve during oral glucose tolerance test.

Study Population:

20 male or female patients with mutations of the insulin receptor, age (Bullet)5 years, at the NIH Clinical Center.

Description of Sites/Facilities Enrolling Participants: Description of Study Intervention:

NIH Clinical Center

Open label study of metreleptin, 0.2 mg/kg/day (max dose 0.24 mg/kg/day).

Conditions: Severe Insulin Resistance
Being tested: Metreleptin
Keywords: Rabson Mendenhall, Type B Insulin Resistance, Type A Insulin Resistance
Medical subject headings: Insulin Resistance, Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MetreleptinDrug
Administered SC twice/day to achieve physiological concentrations that will be effective in improving the severe state of insulin resistance seen in patients with genetic defects on their insulin receptor mutation

Study groups in NCT00085982
Study group	Role	What they receive
Leptin Treatment	Experimental	300 mg of study drug administered via subcutaneous (SC) injections. Receives: Drug: Metreleptin

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in HbA1C
Change in HbA1C at month 12 from baseline.
Measured: Change at month 12 from baseline

Secondary outcomes (2)

Change in Fasting Insulin Level
Change in fasting insulin level at month 12 from baseline
Measured: Change at month 12 from baseline
Change in Fasting Blood Glucose
Change in fasting blood glucose at month 12 from baseline.
Measured: Change at month 12 from baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Aug 20031 Jan 2030

First posted21 Jun 2004 (estimated)
Study start21 Aug 2003
Primary completion23 Oct 2019
Study completion1 Jan 2030 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Severe Insulin ResistanceStudies 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: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00085982
Sponsor's protocol ID: 030257
Other IDs: 03-DK-0257
Status last verified: Dec 2024
First submitted: 18 Jun 2004
Last updated: 30 Jan 2025
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Sekizkardes H, Chung ST, Chacko S, Haymond MW, Startzell M, Walter M, Walter PJ, Lightbourne M, Brown RJ. Free fatty acid processing diverges in human pathologic insulin resistance conditions. J Clin Invest. 2020 Jul 1;130(7):3592-3602. doi: 10.1172/JCI135431.
PubMed 32191645
Okawa MC, Tuska RM, Lightbourne M, Abel BS, Walter M, Dai Y, Cochran E, Brown RJ. Insulin Signaling Through the Insulin Receptor Increases Linear Growth Through Effects on Bone and the GH-IGF-1 Axis. J Clin Endocrinol Metab. 2023 Dec 21;109(1):e96-e106. doi: 10.1210/clinem/dgad491.
PubMed 37595266
Okawa MC, Cochran E, Lightbourne M, Brown RJ. Long-Term Effects of Metreleptin in Rabson-Mendenhall Syndrome on Glycemia, Growth, and Kidney Function. J Clin Endocrinol Metab. 2022 Feb 17;107(3):e1032-e1046. doi: 10.1210/clinem/dgab782.
PubMed 34718628
Brown RJ, Cochran E, Gorden P. Metreleptin improves blood glucose in patients with insulin receptor mutations. J Clin Endocrinol Metab. 2013 Nov;98(11):E1749-56. doi: 10.1210/jc.2013-2317. Epub 2013 Aug 22.
PubMed 23969187