Effect of Metreleptin Therapy in the Treatment of Severe Insulin Resistance

NCT00085982 | Active Not Recruiting Phase 2 Results FDA Drug

• 2 other identifiers: 03025703-DK-0257
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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. 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).

Conditions

Severe Insulin Resistance

Keywords

Rabson Mendenhall; Type B Insulin Resistance; Type A Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Change in HbA1C

  Change in HbA1C at month 12 from baseline.

  Change at month 12 from baseline

Secondary Outcomes (2)

• Change in Fasting Insulin Level

  Change at month 12 from baseline

• Change in Fasting Blood Glucose

  Change at month 12 from baseline

Study Arms (1)

Leptin Treatment

EXPERIMENTAL

300 mg of study drug administered via subcutaneous (SC) injections.

Drug: Metreleptin

Interventions

Metreleptin DRUG

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

Leptin Treatment

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Fasting plasma glucose \>= 126 mg/dL
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 32191645 BACKGROUND

• 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.

  PMID: 37595266 DERIVED

• 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.

  PMID: 34718628 DERIVED

• 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.

  PMID: 23969187 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Insulin Resistance; Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans

Interventions

metreleptin

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Rebecca Brown, MD
• Organization: NIDDK

brownrebecca@mail.nih.gov

301-594-0609

Study Officials

• Rebecca J Brown, M.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2004
• First Posted: June 21, 2004
• Study Start: August 21, 2003
• Primary Completion: October 23, 2019
• Study Completion (Estimated): January 1, 2030
• Last Updated: January 30, 2025
• Results First Posted: December 15, 2021

Record last verified: 2024-12

Locations

US (1)