Effect of Metreleptin Therapy in the Treatment of Severe Insulin Resistance

Severe Insulin Resistance Clinical Trial

Official title:

Phase II Trial of Effect of Metreleptin Therapy in Severe Insulin Resistance

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00085982
• Other study ID #: 030257
• Secondary ID: 03-DK-0257
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 21, 2003
• Est. completion date: January 1, 2030

Study information

• Verified date: June 2023
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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).

Description:

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 11
• Est. completion date: January 1, 2030
• Est. primary completion date: October 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years and older

Eligibility

• INCLUSION CRITERIA:

• 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

• 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

EXCLUSION CRITERIA:

• 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.

Related Conditions & MeSH terms

• Insulin Resistance
• Severe Insulin Resistance

Intervention

Drug:
• Metreleptin
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

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1C	Change in HbA1C at month 12 from baseline.	Change at month 12 from baseline
Secondary	Change in Fasting Insulin Level	Change in fasting insulin level at month 12 from baseline	Change at month 12 from baseline
Secondary	Change in Fasting Blood Glucose	Change in fasting blood glucose at month 12 from baseline.	Change at month 12 from baseline

External Links

•   NIH Clinical Center Detailed Web Page