- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT02235233
Effect of Non-Alcoholic Steatohepatitis (NASH) on the Pharmacokinetics of 99mTechnetium-Mebrofenin
2 de mayo de 2017 actualizado por: University of North Carolina, Chapel Hill
Clinical Study to Investigate the Effect of NASH (Non-alcoholic Steatohepatitis) on the Disposition of 99mTechnetium(Tc)-Mebrofenin in Healthy Subjects Compared to Patients With NASH.
This study is designed to investigate the effect of NASH (non-alcoholic steatohepatitis) on the disposition of 99mTechnetium(Tc)-mebrofenin and to relate changes in 99mTc-mebrofenin disposition to differences in the bile acid profile and Fibroscan Fibrosis Score of healthy subjects compared to patients with NASH.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
This will be an open-label, clinical study in male and female patients with NASH (n=10) and healthy volunteers (n=10) of any race and ethnicity investigating the effect of liver disease on the pharmacokinetics of 99mTechnetium-mebrofenin.
The use of the gamma emitter 99m Tc- labeled mebrofenin will allow real-time assessment of hepatic exposure.
To determine the differences between healthy subjects and patients with NASH, blood and hepatic concentrations will be analyzed by non-compartmental analysis.
Additionally, serum bile acid samples and fibroscan data will be collected to determine whether the bile acid profile and/or fibroscan readings are different between healthy subjects and patients with NASH.
Changes in 99mTc-mebrofenin will be correlated with the patient specific bile acid profile and fibroscan data.
This study will increase our understating of the effect of liver disease on the disposition of medications that undergo transporter-mediated hepatic clearance.
Tipo de estudio
Intervencionista
Inscripción (Actual)
21
Fase
- Fase 1
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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North Carolina
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Chapel Hill, North Carolina, Estados Unidos, 27514
- UNC Hospitals
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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
18 años a 65 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
Sí
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Healthy subjects: defined as being free from significant cardiac, pulmonary, gastrointestinal, hepatic, biliary, renal, hematological, neurological and psychiatric disease as determined by history, physical examination and clinical laboratory test results.
- NASH subjects only: defined as those who have had a recent liver biopsy consistent with NASH without cirrhosis; NAS score >3.
- Fluent and literate in English.
- Willing and able to give informed consent prior to entering the study.
Exclusion Criteria:
- Donation of blood within last 30 days.
- History of significant alcohol abuse (>20g/day) and/or illicit drug use, whether successfully treated or not.
- Inability to abstain from alcohol for 48 hours prior to study visits.
- Inability to fast for 8 hours prior to study sample collection.
- Women who are pregnant, trying to become pregnant, or breast feeding.
- Use of drugs associated with a clinical or histological picture consistent with fatty liver disease or NASH for more than 12 consecutive weeks in the year prior to screening; these include amiodarone, tamoxifen, methotrexate, glucocorticoids, anabolic steroids, tetracyclines, estrogens at doses greater than those used for hormone replacement or valproate/valproic acid
- Type 2 diabetes treated with oral agents other than metformin; these include secretagogues, thiazolidinediones, alpha-glucosidase inhibitors, exenatide and pramlintide.
- Current or recent use of bile acid sequestrants, bile acid derivatives (i.e. ursodiol) or fibric acid derivatives.
- Serum blood glucose reading at study enrollment of >200 mg/dL.
- Current use of antioxidants such as silymarin, vitamin C, glutathione, or non-prescribed complementary alternative medications (including dietary supplements, megadose vitamins, herbal preparations, and special teas) within 30 days prior to screening. A multivitamin and vitamin E at standard doses will be allowed.
- Previous liver biopsy that demonstrated presence of cirrhosis.
- Radiologic imaging consistent with cirrhosis or portal hypertension.
- Evidence of decompensated liver disease defined as any of the following: serum albumin <3.2 g/dL, total bilirubin > 1.5 mg/dL, or PT/INR > 1.3 times normal at screening, or history or presence of ascites, encephalopathy, or bleeding from esophageal varices.
- Serum creatinine of 2.0 mg/dL or greater, or on dialysis, at screening.
- History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, severe psoriasis, rheumatoid arthritis) that could affect the assessment of biomarkers (bile acids or inflammation).
- Primary, secondary or extrahepatic malignancy.
- History of bariatric surgery.
- Participation in a research drug trial, exclusive of the SyNCH Phase I or II trials, within 30 days of screening.
- BMI > 45 kg/m2 at screening (body weight is not within 20% of ideal body weight).
- Inability or unwillingness to give informed consent or abide by the study protocol.
- Estimated weekly strenuous exercise greater than 4 hours per week.
- History or other evidence of illness or any other conditions or drug therapies that would make the patient, in the opinion of the investigator, unsuitable for the study (such as poorly controlled psychiatric disease, coronary artery disease, active gastrointestinal conditions or taking drugs known to interfere with bile acid synthesis or metabolism or the metabolism/transport of other drugs).
- Undergone a radiographic procedure (other than dental X-rays), received radioactive substances, or handled radioactive materials in conjunction with employment within the last twelve months.
- A history of hypersensitivity to 99mTc-mebrofenin, ultrasound gel, dairy products, or their excipients.
- Consumed caffeine (coffee, tea, colas, and chocolate) within 24 hours of the study.
- A history of tobacco use within 12 months of the study.
- Serology positive for Hepatitis B, Hepatitis C or HIV at screening.
- A history of any gastrointestinal or hepatobiliary surgery or disorder.
Healthy Subjects:
- Taking concomitant medications, either prescription and non-prescription (including herbal products and over-the-counter medications), other than oral contraceptives and multivitamins (women stabilized on hormonal methods of birth control will be allowed to participate)
- History or other evidence of liver disease in the opinion of the study investigators.
- BMI > 30 kg/m2 at screening
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: Ciencia básica
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Experimental: Patients with NASH
Each subject will be injected with ~2.5 mCi of Technetium Tc 99M Mebrofenin
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Each subject will be injected with ~2.5 mCi of Technetium Tc 99M Mebrofenin
Otros nombres:
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Comparador activo: Healthy Normal Volunteers
Each subject will be injected with ~2.5 mCi of Technetium Tc 99M Mebrofenin
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Each subject will be injected with ~2.5 mCi of Technetium Tc 99M Mebrofenin
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Hepatic exposure (AUC0→∞)
Periodo de tiempo: 0-180 minutes
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Area under the hepatic concentration-time curve
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0-180 minutes
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Systemic exposure (AUC0 →∞)
Periodo de tiempo: 0-300 minutes
|
Area under the systemic concentration-time curve
|
0-300 minutes
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Cmax (hepatic)
Periodo de tiempo: 0-180 minutes
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Peak mebrofenin concentration in the liver
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0-180 minutes
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Tmax (hepatic)
Periodo de tiempo: 0-180 minutes
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Time to peak concentration of mebrofenin in the liver
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0-180 minutes
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Xurine
Periodo de tiempo: 0-180 minutes
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Mass excreted in urine
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0-180 minutes
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CLuptake
Periodo de tiempo: 0-180 minutes
|
Hepatic uptake clearance
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0-180 minutes
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CLrenal
Periodo de tiempo: 0-180 minutes
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Renal clearance
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0-180 minutes
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Sidney Barritt, M.D., MSCR, University of North Carolina, Chapel Hill
- Director de estudio: Jason R. Slizgi, B.S., UNC School of Pharmacy
- Director de estudio: Kim Brouwer, PharmD, PhD, UNC School of Pharmacy
- Director de estudio: Josh Kaullen, Pharm.D., UNC School of Pharmacy
- Director de estudio: Marijia Ivanovic, Ph.D., UNC Department of Radiology
- Director de estudio: Paul Stewart, Ph.D., UNC School of Public Health
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.
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 (Actual)
1 de abril de 2015
Finalización primaria (Actual)
1 de julio de 2016
Finalización del estudio (Actual)
1 de julio de 2016
Fechas de registro del estudio
Enviado por primera vez
5 de septiembre de 2014
Primero enviado que cumplió con los criterios de control de calidad
8 de septiembre de 2014
Publicado por primera vez (Estimar)
9 de septiembre de 2014
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
5 de mayo de 2017
Última actualización enviada que cumplió con los criterios de control de calidad
2 de mayo de 2017
Última verificación
1 de mayo de 2017
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 13-3362
- 2R01GM041935 (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. .
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