Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
1200 participants
OBSERVATIONAL
1976-02-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Researchers will take 4 to 6 ounces (100-150 ml) of blood from adult patients and may request up to 12 ounces (one unit) of blood if necessary. Skin samples may be taken for a biopsy if further genetic testing is necessary. In addition some patients may be asked not to eat for up to 72 hours prior to testing.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Defining the Physiological Mechanisms of Risk Genes for Hyperglycaemia, Insulin Resistance and Type 2 Diabetes
NCT02723110
Insulin Receptor Substrate 1 (IRS-1) Regulation in Insulin Resistance
NCT01240252
Admixture Mapping of Ethnic and Racial Insulin Complex Outcomes
NCT00726778
Epigenetics and the Origin of Muscle Insulin Resistance in Humans
NCT01726491
Defining the Human Insulin Resistance Molecular Network; SIGNATURE
NCT07255807
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Insulin is the key hormone responsible for regulating the level of glucose in plasma. In several disease states (e.g., obesity, type 2 diabetes, and acromegaly), the target cells are resistant to insulin action. Insulin resistance leads to metabolic complications including diabetes, dyslipidemia, cardiovascular disease, non-alcoholic fatty liver disease, and reproductive dysfunction. The intramural research program of the NIDDK has a long history of studying patients with rare disorders of extreme insulin resistance. We use what is learned from these rare patients both to develop therapeutics for rare diseases, and to apply what is learned to understand more common forms of insulin resistance.
Objectives:
Primary Objectives: (1) To understand the pathophysiology of insulin resistance and its relationship to diabetes, dyslipidemia, cardiovascular disease, liver disease, kidney disease, reproductive function, bone disease, and other organ dysfunction, (2) To study the molecular genetics underlying various causes of insulin resistance and diabetes mellitus, (3) To understand the natural history of insulin resistance disorders, including their response to FDA approved therapies, and (4) To conduct ex vivo studies of the physiology and pathophysiology underlying disorders of insulin resistance, and possible treatments for these disorders, using cells and tissues collected in this study.
Endpoints:
Primary Endpoint: Genetic causes of insulin resistance
Secondary Endpoints: Diabetes control (hemoglobin A1c) and complications (rates of micro- and macrovascular disease)
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
COHORT
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Healthy Volunteers
Healthy Volunteers
HR-pQCT scan
HR-pQCT is a non-invasive, low-dose three-dimensional imaging method used to evaluate volumetric bone mineral density and bone microarchitecture of peripheral skeletal sites, including distal radius and distal tibia. HR-pQCT has an ability to differentiate between cortical and trabecular bone compartments providing density and structure parameters.
Patients with severe insulin resistance
patients with severe insulin resistance manifesting with acanthosis nigricans, hyperinsulinemia, type A and B insulin resistance syndromes, and patients with lipodystrophy.
HR-pQCT scan
HR-pQCT is a non-invasive, low-dose three-dimensional imaging method used to evaluate volumetric bone mineral density and bone microarchitecture of peripheral skeletal sites, including distal radius and distal tibia. HR-pQCT has an ability to differentiate between cortical and trabecular bone compartments providing density and structure parameters.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
HR-pQCT scan
HR-pQCT is a non-invasive, low-dose three-dimensional imaging method used to evaluate volumetric bone mineral density and bone microarchitecture of peripheral skeletal sites, including distal radius and distal tibia. HR-pQCT has an ability to differentiate between cortical and trabecular bone compartments providing density and structure parameters.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patients with evidence for insulin resistance or a disorder associated with severe insulin resistance, including:
* Patients with various syndromes of lipodystrophy
* Patients with known or suspected mutations on the insulin receptor gene
* Patients with known or suspected autoantibodies to the insulin receptor
* Patients with other severe forms of insulin resistance
* Family members of patients, above
* Healthy control subjects without insulin resistance
* Patients with evidence for severe insulin resistance or a disorder associated with severe insulin resistance must meet all of the following criteria:
* Suspected severe insulin resistance, or a disorder associated with severe insulin resistance, as evidenced by one or more of the following:
* Hyperinsulinemia (i.e. fasting insulin \>30microU/mL)
* High insulin requirement (\> 2 units per kg per day or \> 200 units total per day)
* Phenotypic features suggesting a defect in glucose/lipid metabolism:
* Acanthosis nigricans
* Lipodystrophy/abnormal fat distribution
* Xanthomata
* Fatty liver
* Known or suspected mutations of the insulin receptor gene
* Known or suspected autoantibodies to the insulin receptor
* Age \>= 6 months
* Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
* Family members of patients, above (either affected or unaffected) must meet all of the following criteria:
* Biological relatives of patients in category (1) in whom a genetic cause of insulin resistance is known or suspected.
* Age \>= 6 months
* Ability of subject (and/or legal guardian, for minor subjects) to understand and the willingness to sign a written informed assent/consent document.
* Healthy control subjects Cohort 1 must meet all of the following criteria.
* Ability of subject (and/or legal guardian, for minor subjects) to understand and the willingness to sign a written informed assent/consent document.
* In good general health with no known active medical conditions as evidenced by medical history
* Age \>= 12 years
* Fasting glucose \<100 mg/dL
* HbA1c \<5.7%
* Fasting triglycerides \<150 mg/dL
* Fasting insulin \<30 mcU/mL
* BMI \<27 kg/m\^2 or \<90th percentile for age/sex (whichever is lower)
Exclusion Criteria
--none
* Family members of patients, above
--Pregnant at the time of enrollment
* Healthy control subjects Cohort 1
* Current use of prescription or non-prescription medication. Certain exceptions are permitted, including topical medications, vitamins, and hormonal contraceptives. Other medications may be permitted at the discretion of the investigators.
* Recent (past 2 months) use of drugs or supplements that alter glucose or lipid metabolism (e.g. niacin, fish oil, red yeast rice)
* History of diabetes or abnormal glucose tolerance
* Psychiatric or cognitive disorder that will, in the opinion of the investigators, limit the subject's ability to provide informed consent/assent, or to comply with study procedures
* Pregnant or lactating
* Abnormal screening labs, including the following:
* ALT or AST more than 1.5 times the upper limit of normal
* Glycosuria
* Clinically significant anemia
* Low eGFR (\<60 mL/min/1.73m\^2)
* Any other abnormality that, in the opinion of the investigator, will increase risk to the subject from participation, or interfere with interpretation of study data
6 Months
120 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Rebecca J Brown, M.D.
Role: PRINCIPAL_INVESTIGATOR
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
References
Explore related publications, articles, or registry entries linked to this study.
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.
Walzer D, Turcu AF, Jha S, Abel BS, Auchus RJ, Merke DP, Brown RJ. Excess 11-Oxygenated Androgens in Women With Severe Insulin Resistance Are Mediated by Adrenal Insulin Receptor Signaling. J Clin Endocrinol Metab. 2022 Aug 18;107(9):2626-2635. doi: 10.1210/clinem/dgac365.
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.
Meral R, Malandrino N, Walter M, Neidert AH, Muniyappa R, Oral EA, Brown RJ. Endogenous Leptin Concentrations Poorly Predict Metreleptin Response in Patients With Partial Lipodystrophy. J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1739-e1751. doi: 10.1210/clinem/dgab760.
Nguyen ML, Sachdev V, Burklow TR, Li W, Startzell M, Auh S, Brown RJ. Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy. J Clin Endocrinol Metab. 2021 Oct 21;106(11):e4327-e4339. doi: 10.1210/clinem/dgab499.
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.
Klubo-Gwiezdzinska J, Lange M, Cochran E, Semple RK, Gewert C, Brown RJ, Gorden P. Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type B Insulin Resistance: A Prospective Cohort Study. Diabetes Care. 2018 Nov;41(11):2353-2360. doi: 10.2337/dc18-0884. Epub 2018 Sep 10.
Brown RJ, Joseph J, Cochran E, Gewert C, Semple R, Gorden P. Type B Insulin Resistance Masquerading as Ovarian Hyperthecosis. J Clin Endocrinol Metab. 2017 Jun 1;102(6):1789-1791. doi: 10.1210/jc.2016-3674.
Kassai A, Muniyappa R, Levenson AE, Walter MF, Abel BS, Ring M, Taylor SI, Biddinger SB, Skarulis MC, Gorden P, Brown RJ. Effect of Leptin Administration on Circulating Apolipoprotein CIII levels in Patients With Lipodystrophy. J Clin Endocrinol Metab. 2016 Apr;101(4):1790-7. doi: 10.1210/jc.2015-3891. Epub 2016 Feb 22.
Related Links
Access external resources that provide additional context or updates about the study.
NIH Clinical Center Detailed Web Page
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
76-DK-0006
Identifier Type: -
Identifier Source: secondary_id
760006
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.