Effect of Metreleptin Therapy in the Treatment of Severe Insulin Resistance

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Primary Purpose

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Metreleptin

About this trial

This is an interventional treatment trial for Severe Insulin Resistance focused on measuring Rabson Mendenhall, Type B Insulin Resistance, Type A Insulin Resistance

Eligibility Criteria

5 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Leptin Treatment

Arm Description

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

Outcomes

Primary Outcome Measures

Change in HbA1C

Change in HbA1C at month 12 from baseline.

Secondary Outcome Measures

Change in Fasting Insulin Level

Change in fasting insulin level at month 12 from baseline

Change in Fasting Blood Glucose

Change in fasting blood glucose at month 12 from baseline.

Full Information

NCT ID

NCT00085982

First Posted

June 18, 2004

Last Updated

June 9, 2023

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT00085982

Brief Title

Effect of Metreleptin Therapy in the Treatment of Severe Insulin Resistance

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 21, 2003 (Actual)

Primary Completion Date

October 23, 2019 (Actual)

Study Completion Date

January 1, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Severe Insulin Resistance

Keywords

Rabson Mendenhall, Type B Insulin Resistance, Type A Insulin Resistance

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

11 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Leptin Treatment

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Metreleptin

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in HbA1C

Description

Change in HbA1C at month 12 from baseline.

Time Frame

Change at month 12 from baseline

Secondary Outcome Measure Information:

Title

Change in Fasting Insulin Level

Description

Change in fasting insulin level at month 12 from baseline

Time Frame

Change at month 12 from baseline

Title

Change in Fasting Blood Glucose

Description

Change in fasting blood glucose at month 12 from baseline.

Time Frame

Change at month 12 from baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rebecca J Brown, M.D.

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center, 9000 Rockville Pike

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

32191645

Citation

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.

Results Reference

background

PubMed Identifier

34718628

Citation

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.

Results Reference

derived

PubMed Identifier

23969187

Citation

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.

Results Reference

derived

Links:

URL

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2003-DK-0257.html

Description

NIH Clinical Center Detailed Web Page

Severe Insulin Resistance

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial