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- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT03174171
Open-label Study on Treatment of Primary Aldosteronism With Everolimus
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
The purpose of this study is to evaluate everolimus as an aldosterone-lowering drug in treatment of primary aldosteronism.
Primary aldosteronism is defined as a group of disorders in which aldosterone production is inappropriately high and relatively autonomous from regulation by the renin-angiotensin-aldosterone system. It often presents with increased blood pressure and constitutes the most common cause of endocrine hypertension. It is associated with an increased risk of cardiovascular complications, structural and functional renal abnormalities and metabolic syndrome. The goal of primary aldosteronism treatment is to prevent mortality and morbidity associated with hypertension, hypokalemia and direct aldosterone-associated organ damage.
Treatment depends on the underlying cause of primary aldosteronism. In general, patients with aldosterone-producing adenoma and unilateral adrenal hyperplasia are recommended to have adrenalectomy while patients with bilateral adrenal hyperplasia and those not willing to obtain surgery are offered targeted treatment with mineralocorticoid receptor antagonists. However, the use of mineralocorticoid receptor antagonist is related to side effects that include breast tenderness, gynecomastia, sexual dysfunction and menstrual irregularities.
The primary purpose of this proof-of-concept study is to evaluate whether inhibition of adrenocortical mammilian target of rapamycin (mTOR) signalling with everolimus decreases circulating aldosterone levels. The study also aims to determine whether potential changes in aldosterone levels result solely from a direct effect of everolimus on the adrenal gland or could be caused by changes in aldosterone metabolism and/or levels of canonical regulators of adrenal function (ACTH, AngII). The secondary purpose of this study is to test whether everolimus treatment ameliorates hypertension, improves cardiac function and to better understand molecular mechanisms leading to the development of primary aldosteronism.
Participants will receive Everolimus 0.75mg b.i.d. orally for a duration of 14 days. Blood pressure measurements, haemodynamic measurements, blood tests, 24h urine collection and saline Infusion tests will be conducted in order to compare changes in blood pressure, cardiac and kidney function, aldosterone and steroid hormone metabolite levels, activity of the renin-angiotensin-aldosterone system before and after treatment.
In patients undergoing adrenalectomy, adrenocortical cells will be isolated and primary adrenocortical cell cultures will be established from excised adrenal glands. Cultured cells will be treated with mTOR inhibitors and their proliferation and steroidogenic potential will be assessed. Cells treated with mTOR inhibitors will be subjected to transcriptomic, proteomic and phosphoproteomic analyses that will allow identification of mTOR signaling effectors in the adrenal cortex and to better understand molecular mechanisms leading to the development of primary aldosteronism.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Basel Stadt
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Basel, Basel Stadt, Suiza, 4031
- University Hospital Basel
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Patient with primary aldosteronism
- Age ≥ 18 years
- Office blood pressure <160/90 mmHg on antihypertensive therapy
- For subjects with reproductive potential, willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study
Exclusion Criteria:
- Signs of current infection
- Neutropenia (leukocyte count < 1.5 × 109/L or absolute neutrophil count (ANC) < 0.5 × 109/L)
- Anemia (hemoglobin < 11 g/dL for males, < 10 g/dL for females)
- Clinically significant kidney or liver disease (creatinine > 1.5 mg/dL, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 × ULN, alkaline phosphatase > 2 × ULN, total bilirubin > 1.5 × ULN)
- Current immunosuppressive treatment or documented immunodeficiency
- Uncontrolled congestive heart failure
- Currently pregnant or breastfeeding
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Intervention
Everolimus 0.75 mg b.i.d.
orally for 14 days.
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Everolimus 0.75 mg b.i.d.
orally for 14 days.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Aldosterone level
Periodo de tiempo: 28 days
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Change in aldosterone level after saline infusion test after the treatment period (Day 15) and after the washout period (Day 28) compared to baseline (Day 0).
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28 days
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Blood pressure values
Periodo de tiempo: 28 days
|
Change in mean systolic and diastolic blood pressure during standardized office and home blood pressure measurement after the treatment period (Day 15) and after the washout period (Day 28) compared to baseline (Day 0).
|
28 days
|
Kidney function
Periodo de tiempo: 28 days
|
Change in albumin in 24 hour-urine after the treatment period (Day 15) and after the washout period (Day 28) compared to baseline (Day 0).
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28 days
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Steroid hormones in serum
Periodo de tiempo: 28 days
|
Change in steroid hormones in serum in 24h-urine after the treatment period (Day 15) and after the washout period (Day 28) compared to baseline (Day 0).
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28 days
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Level of plasma renin activity
Periodo de tiempo: 28 days
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Change in Renin-angiotensin-aldosterone System after the treatment period (Day 15) and after the washout period (Day 28) compared to baseline (Day 0).
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28 days
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Level of Potassium
Periodo de tiempo: 28 days
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Change in potassium level and need of potassium substitution after the treatment period (Day 15) and after the washout period (Day 28) compared to baseline (Day 0).
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28 days
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Steroid hormone metabolites in urine
Periodo de tiempo: 28 days
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Change in steroid hormone metabolites in 24h-urine after the treatment period (Day 15) and after the washout period (Day 28) compared to baseline (Day 0).
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28 days
|
Level of plasma ACTH
Periodo de tiempo: 28 days
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Change in the Renin-angiotensin-aldosterone system after the treatment period (Day 15) and after the washout period (Day 28) compared to baseline (Day 0).
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28 days
|
Level of plasma angiotensin II (ATII)
Periodo de tiempo: 28 days
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Change in the Renin-angiotensin-aldosterone system after the treatment period (Day 15) and after the washout period (Day 28) compared to baseline (Day 0).
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28 days
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Marc Y Donath, Prof., University Hospital, Basel, Switzerland
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- EPA
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los 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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