Effect of Metreleptin Therapy in the Treatment of Severe Insulin Resistance

Phase 2

Active, not recruiting

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

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).

Detailed 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 & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Leptin Treatment	Metreleptin	300 mg of study drug administered via subcutaneous (SC) injections.

Primary Outcome Measures

Name	Time	Method
Change in HbA1C	Change at month 12 from baseline	Change in HbA1C at month 12 from baseline.

Secondary Outcome Measures

Name	Time	Method
Change in Fasting Blood Glucose	Change at month 12 from baseline	Change in fasting blood glucose at month 12 from baseline.
Change in Fasting Insulin Level	Change at month 12 from baseline	Change in fasting insulin level at month 12 from baseline