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| ID | Type | Description | Link |
|---|---|---|---|
| 03-DK-0257 |
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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).
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Leptin Treatment | Experimental | 300 mg of study drug administered via subcutaneous (SC) injections. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in HbA1C | Change in HbA1C at month 12 from baseline. | Change at month 12 from baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Fasting Insulin Level | Change in fasting insulin level at month 12 from baseline | Change at month 12 from baseline |
| Change in Fasting Blood Glucose | Change in fasting blood glucose at month 12 from baseline. |
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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:
EXCLUSION CRITERIA:
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| Name | Affiliation | Role |
|---|---|---|
| Rebecca J Brown, M.D. | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32191645 | Background | 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. | |
| 37595266 | Derived | 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. |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Leptin Treatment | 300 mg of study drug administered via subcutaneous (SC) injections. 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Leptin Treatment | 300 mg of study drug administered via SC injections. 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in HbA1C | Change in HbA1C at month 12 from baseline. | Posted | Mean | Standard Deviation | percent | Change at month 12 from baseline |
|
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Leptin Treatment | 300 mg of study drug administered via SC injections. 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute kidney injury | Renal and urinary disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acrochordon | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rebecca Brown, MD | NIDDK | 301-594-0609 | brownrebecca@mail.nih.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 5, 2021 | Nov 12, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| C562710 | Diabetes Mellitus, Insulin-Resistant, with Acanthosis Nigricans |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C415771 | metreleptin |
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| Change at month 12 from baseline |
| 34718628 | 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. |
| 23969187 | 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. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| A1c | Mean | Standard Deviation | percent |
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| Fasting blood glucose | Mean | Standard Deviation | mg/dL |
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| Fasting Insulin | Mean | Standard Deviation | mcU/mL |
|
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| Secondary | Change in Fasting Insulin Level | Change in fasting insulin level at month 12 from baseline | Posted | Mean | Standard Deviation | mcU/mL | Change at month 12 from baseline |
|
|
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| Secondary | Change in Fasting Blood Glucose | Change in fasting blood glucose at month 12 from baseline. | Posted | Mean | Standard Deviation | mg/dL | Change at month 12 from baseline |
|
|
|
| 0 |
| 11 |
| 5 |
| 11 |
| 7 |
| 11 |
| Brain lesion | Nervous system disorders | Non-systematic Assessment |
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| DKA | Endocrine disorders | Non-systematic Assessment |
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| Edema | General disorders | Non-systematic Assessment |
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| Hyperglycemia | Endocrine disorders | Non-systematic Assessment |
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| papillary carcinoma of thyroid | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
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| Seizure | Nervous system disorders | Non-systematic Assessment |
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| Septic shock | Infections and infestations | Non-systematic Assessment |
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| Urinary tract infection | Infections and infestations | Non-systematic Assessment |
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| Alcohol withdrawal | Psychiatric disorders | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | Non-systematic Assessment |
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| Candidiasis | Infections and infestations | Non-systematic Assessment |
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| Cataract | Eye disorders | Non-systematic Assessment |
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| Cerumen impaction | Ear and labyrinth disorders | Non-systematic Assessment |
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| Cholesteatoma | Ear and labyrinth disorders | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
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| COVID-19 | Infections and infestations | Non-systematic Assessment |
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| Cracked tooth | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Dental abscess | Infections and infestations | Non-systematic Assessment |
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| Depression | Psychiatric disorders | Non-systematic Assessment |
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| Edema | General disorders | Non-systematic Assessment |
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| Elevated lactate | Metabolism and nutrition disorders | Non-systematic Assessment |
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| GERD | Gastrointestinal disorders | Non-systematic Assessment |
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| Glaucoma | Eye disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Hyperglycemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Hyperkalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Hypoglycemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Hypokalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Indigestion | Gastrointestinal disorders | Non-systematic Assessment |
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| Ketosis | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Kidney stone | Renal and urinary disorders | Non-systematic Assessment |
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| Mastoidectomy & tympanostomy tube placement | Surgical and medical procedures | Non-systematic Assessment |
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| Mitral & tricupsid valve regurgitation | Cardiac disorders | Non-systematic Assessment |
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| Pain | General disorders | Non-systematic Assessment |
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| Seizure | Nervous system disorders | Non-systematic Assessment |
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| Shortness of breath | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Syncope | Nervous system disorders | Non-systematic Assessment |
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| Throid nodule | Endocrine disorders | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
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| Weight loss | Metabolism and nutrition disorders | Non-systematic Assessment |
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