Effect of Insulin Sensitizer Therapy on Atherothrombotic and Inflammatory Profiles Associated With Insulin Resistance
7 de octubre de 2013 actualizado por: K. Sreekumaran Nair, Mayo Clinic
The objective of this study is to determine whether targeted pharmacological improvement of insulin sensitivity will normalize the associated elevations of thrombotic and inflammatory cardiovascular disease (CVD) biomarkers in individuals with insulin resistance.
Descripción general del estudio
Estado
Terminado
Intervención / Tratamiento
Descripción detallada
Individuals with diabetes mellitus (DM) are disproportionately affected by atherothrombotic disorders, including cardiovascular, cerebrovascular, and peripheral vascular diseases. Atherothrombotic disease risk and mortality are also increased with metabolic syndrome, a constellation of risk factors present in more than 34% of adults, even in absence of diabetes. Yet, large clinical trials of diabetes therapies have shown that conventional cardiovascular disease (CVD) risk factors, specifically hyperglycemia and hypertension, do not fully account for increased CVD risk associated with DM.
There may be an etiologic link among insulin resistance, inflammation and thrombotic events. This study seeks to determine if certain two diabetes medications (the insulin sensitizing medications) will affect certain biomarkers (or laboratory tests) for CVD in individuals with untreated DM or impaired fasting glucose.
Patients will be screened for inclusion into this this double-blinded, randomized), placebo-controlled study. If inclusion criteria are met and exclusion criteria not met, patients will be enrolled in the the study. Half of the subjects will be randomized (like the flip of a coin) to take two insulin sensitizing, anti-diabetic drugs pioglitazone (Actos) and metformin (Glucophage) taken together for three months and the other half of the subjects will take corresponding placebo (dummy) tablets.
Laboratory measurements will be obtained on the morning(s) following the two in-patient overnight stays in the Mayo Clinic Clinical Research Unit. The first stay will be at baseline and the second stay will be 3 months after baseline. Insulin sensitivity will be measured in the morning following a standardized meal the preceding night, and after an overnight fast.
The changes (from baseline to 3 months) in insulin sensitivity, glycemic control, the lipid profile, thrombotic markers and inflammatory markers will be determined and compared between the two arms of the study (placebo versus insulin sensitizing drugs).
Tipo de estudio
Intervencionista
Inscripción (Actual)
28
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
20 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion criteria:
- We will study 30 patients with Type 2 Diabetes or impaired fasting glucose (15 men & 15 women) who are > 20 years old.
- Only patients who use lifestyle modification to manage their diabetes and are not on any oral hypoglycemic agents or insulin will be included.
- We will enroll subjects who have fasting glucose concentration greater than 100 mg/dl on two consecutive occasions and have a Body Mass Index between 27-36 kg/m^2.
Exclusion Criteria:
- We will exclude patients whose blood glucose is above 180 mg/dl. This will avoid the need to perform home glucose monitoring and the potential of unblinding the study by the volunteers.
- Patients taking oral hypoglycemic agents or insulin would be excluded.
- Any diseases such as active cardiovascular disease, liver diseases, kidney failure (males with serum creatinine >= 1.5mg/dl, females >=1.4 mg/dl), active endocrinopathies, debilitating chronic disease, anemia, symptoms of undiagnosed illness, history of alcoholism (alcohol use > 4oz/day) or substance abuse, chronic neurological diseases including Alzheimer's disease, stroke, etc, myopathies or any other active disease that may potentially affect the outcome measures.
- Patients on medicines such as beta blockers, corticosteroids, tricyclics, benzodiazepines, opiates, barbiturates, anticoagulants and any other drugs or preparations that may affect mitochondrial function will be excluded.
- People allergic to any of the class of drug such as lidocaine will also be excluded.
- People with pacemakers, certain aneurysm clips and claustrophobia will also be excluded as they cannot undergo magnetic resonance imaging.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador activo: Insulin Sensitizer Therapy
Two insulin sensitizing drugs will be taken together for 3 months; metformin 1000 mg twice daily plus pioglitazone 45 mg daily.
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To minimize side effects the metformin will be initiated at 500 mg twice daily with meals and increased to 1 gm twice daily with meals after two weeks and continue to a total of 3 months of dosing.
Otros nombres:
To minimize side effects, the pioglitazone will be initiated at 30 mg daily and increased to 45 mg daily after two weeks, and continue to a total of 3 months of dosing.
Otros nombres:
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Comparador de placebos: Placebo
Placebo tablets were used to match the active comparator drugs and dosing regimen.
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Placebo tablets matching the metformin and pioglitazone tablets are given in the same regimen as the active drug arm for 3 months.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Change From Baseline in Insulin Sensitivity as Measured by Glucose Infusion Rate (GIR)
Periodo de tiempo: Baseline, 3 months
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Insulin sensitivity was measured the morning after an overnight fast during an in-patient stay in the Clinical Research Unit & was determined by the mean GIR necessary to maintain euglycemia during a hyperinsulinemic (1.5 mcIU/kg of FFM per minute)-euglycemic (85-95 mg/dL) clamp.
The clamp is an 8 hour process where a hand vein is catheterized to collect blood samples and intravenous lines are used to infuse glucose, saline, insulin, phenylalanine and amino acid solutions at at pre-specified times/rates.
The mean GIR was calculated as the rate per kilograms of fat-free mass (FFM) during 4 hours of steady-state (hours 4-8 of the 8 hour clamp) reported as micromols/kilogram of FFM per minute.
The FFM was measured by dual-energy x-ray absorptiometry (DEXA) scan.
Insulin was infused with 5% essential amino acid solution (3mL/kg of FFM/hour) to prevent the insulin-dependent decrease of amino acids during insulin infusion.
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Baseline, 3 months
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change From Baseline in Fasting Blood Glucose Level
Periodo de tiempo: Baseline, 3 months
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Glucose (sugar) was measured in the blood and reported in milligrams per deciliter (mg/dL).
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Baseline, 3 months
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Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Periodo de tiempo: Baseline, 3 months
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HbA1c is a measure of average blood sugar levels over the preceding 3 month period.
HbA1c was measured by ion-exchange chromatography and reported as a percentage.
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Baseline, 3 months
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Change From Baseline in Insulin Levels
Periodo de tiempo: Baseline, 3 months
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Insulin levels in the blood were measured by immunoenzymatic assay and reported in micro International Units per milliliter (mcIU/mL).
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Baseline, 3 months
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Change From Baseline in Lipid Profile
Periodo de tiempo: Baseline, 3 months
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Change in lipids were measured by the change from baseline to 3 months of triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C).
All were reported in milligrams/deciliter (mg/dL).
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Baseline, 3 months
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Change From Baseline in the Thrombotic Biomarker Fibrinogen
Periodo de tiempo: Baseline, 3 months
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Fibrinogen was measured by thrombin clotting rate assay (Beckman Coulter, Inc. Brea, California) and reported in milligrams/deciliter (mg/dL).
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Baseline, 3 months
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Change From Baseline in the Thrombotic Biomarker Plasminogen Activator Inhibitor-1 (PAI-1)
Periodo de tiempo: Baseline, 3 months
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PAI-1 was measured by enzyme-linked immunosorbent assay (Diagnostica Stago Inc., Parsippany, New Jersey) and reported in nanograms per milliliter (ng/mL).
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Baseline, 3 months
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Change From Baseline in the Inflammatory Biomarker Interleukin 6 (IL-6)
Periodo de tiempo: Baseline, 3 months
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IL-6 is an inflammatory cytokine and reported in picograms per deciliter (pg/dL).
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Baseline, 3 months
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Change From Baseline in the Inflammatory Biomarker C-Reactive Protein (CRP)
Periodo de tiempo: Baseline, 3 months
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CRP is an inflammatory cytokine and is reported in milligrams per deciliter (mg/dL).
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Baseline, 3 months
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Change From Baseline in Inflammatory Biomarker Tumor Necrosis Factor-alpha (TNF-α)
Periodo de tiempo: Baseline, 3 month
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TNF-α is an inflammatory cytokine and is reported in picograms/milliliter (pg/mL).
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Baseline, 3 month
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Change From Baseline in the Inflammatory Biomarker Adiponectin
Periodo de tiempo: Baseline, 3 months
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Adiponectin is an anti-inflammatory cytokine and is reported in milligrams per milliliter (mg/mL).
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Baseline, 3 months
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change From Baseline in Body Mass Index
Periodo de tiempo: Baseline, 3 months
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Body Mass Index (BMI) is a health index for comparing weight to height.
BMI is a person's weight in kilograms (kg) divided by his or her height in meters squared.
The body mass index is an indication if a person is at a suitable weight for his height on an approximation of body fat.
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Baseline, 3 months
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Change From Baseline in Body Fat
Periodo de tiempo: Baseline, 3 months
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Body fat is reported as a percentage of body weight.
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Baseline, 3 months
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Change From Baseline in Fat-Free Mass (FFM)
Periodo de tiempo: Baseline, 3 months
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FFM was measured using dual energy x-ray absorptiometry (DEXA) scans and is reported in kilograms (kg).
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Baseline, 3 months
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- McCoy RG, Irving BA, Soop M, Srinivasan M, Tatpati L, Chow L, Weymiller AJ, Carter RE, Nair KS. Effect of insulin sensitizer therapy on atherothrombotic and inflammatory profiles associated with insulin resistance. Mayo Clin Proc. 2012 Jun;87(6):561-70. doi: 10.1016/j.mayocp.2012.02.014. Erratum In: Mayo Clin Proc. 2013 Aug;88(8):903-4.
- Irving BA, Carter RE, Soop M, Weymiller A, Syed H, Karakelides H, Bhagra S, Short KR, Tatpati L, Barazzoni R, Nair KS. Effect of insulin sensitizer therapy on amino acids and their metabolites. Metabolism. 2015 Jun;64(6):720-8. doi: 10.1016/j.metabol.2015.01.008. Epub 2015 Jan 22.
Enlaces Útiles
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de agosto de 2005
Finalización primaria (Actual)
1 de agosto de 2010
Finalización del estudio (Actual)
1 de agosto de 2010
Fechas de registro del estudio
Enviado por primera vez
26 de febrero de 2007
Primero enviado que cumplió con los criterios de control de calidad
5 de marzo de 2007
Publicado por primera vez (Estimar)
6 de marzo de 2007
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
31 de octubre de 2013
Última actualización enviada que cumplió con los criterios de control de calidad
7 de octubre de 2013
Última verificación
1 de octubre de 2013
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 05-004002
- UL1RR024150 (Subvención/contrato del NIH de EE. UU.)
- KL2RR024151 (Subvención/contrato del NIH de EE. UU.)
- R01DK041973 (Subvención/contrato del NIH de EE. UU.)
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .